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Sample records for lesser extent mapk

  1. Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells.

    Science.gov (United States)

    Zeng, Huawei; Taussig, David P; Cheng, Wen-Hsing; Johnson, LuAnn K; Hakkak, Reza

    2017-01-01

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

  2. Dietary fish oil, and to a lesser extent the fat-1 transgene, increases astrocyte activation in response to intracerebroventricular amyloid-β 1-40 in mice.

    Science.gov (United States)

    Hopperton, Kathryn E; James, Nicholas C E; Mohammad, Dana; Irfan, Maha; Bazinet, Richard P

    2017-11-07

    Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer's disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear. Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-β 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques. GFAP increased in all groups in response to amyloid-β, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-β infusion than wildtype safflower animals. Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-β 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-β than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.

  3. Desmoid tumor within lesser sac

    Directory of Open Access Journals (Sweden)

    Čolović Radoje

    2006-01-01

    Full Text Available Desmoid tumors or fibromatoses comprise a number of benign fibrous proliferative lesions that have local infiltrative growth and tendency to recur after incomplete excision. They never metastasize. The authors present a 31-year old woman who, due to epigastric pain and palpable mass detected on presentation, underwent the excision of firm tumorous mass, 210x140x115mm in diameter, from the lesser sac. Compressing the splenic vein, the tumor caused left-sided portal hypertension which subsided after the mass was removed. The recovery was uneventful. The histological examination verified typical desmoid tumor. Twelve years after surgery, the patient remained symptom-free with no signs of recurrence.

  4. LncMAPK6 drives MAPK6 expression and liver TIC self-renewal.

    Science.gov (United States)

    Huang, Guanqun; Jiang, Hui; He, Yueming; Lin, Ye; Xia, Wuzheng; Luo, Yuanwei; Liang, Min; Shi, Boyun; Zhou, Xinke; Jian, Zhixiang

    2018-05-15

    Liver tumor initiating cells (TICs) have self-renewal and differentiate capacities, and largely contribute to tumor initiation, metastasis and drug resistance. MAPK signaling is a critical pathway in many biological processes, while its role in liver TICs hasn't been explored. Online-available dataset was used for unbiased screening. Liver TICs were examined CD133 FACS or oncosphere formation. TIC self-renewal was detected by oncosphere formation and tumor initiation assay. LncRNA function was detected by loss of function or gain of function assays. The molecular mechanism of lncRNA was explored by RNA pulldown, RNA immunoprecipitation, ChIP, western blot and double FISH. Here, we examined the expression profiles of MAPK components (MAPKs, MAP2Ks, MAP3Ks, MAP4Ks), and found MAPK6 is most highly expressed in liver cancer samples. Moreover, a divergent lncRNA (long noncoding RNA) of MAPK6, termed lncMAPK6 here, is also overexpressed along with liver tumorigenesis. LncMAPK6 promotes liver tumor propagation and TIC self-renewal through MAPK6. LncMAPK6 interacts with and recruits RNA polymerase II to MAPK6 promoter, and finally activates the transcription of MAPK6. Through MAPK6 transcriptional regulation, lncMAPK6 drives MARK signaling activation. LncMAPK6-MAPK6 pathway can be used for liver TIC targeting. Altogether, lncMAPK6 promotes MARK signaling and the self-renewal of liver TICs through MAPK6 expression. MAPK6 was the most highly expressed MAPK component in liver cancer and liver TICs and lncMAPK6 participated in the transcriptional regulation of MAPK6in cis. This work revealed the importance role of MAPK signaling in liver TIC self-renewal and added a new layer for liver TIC and MAPK6 expression regulation.

  5. MAPK cascades in guard cell signal transduction

    Directory of Open Access Journals (Sweden)

    Yuree eLee

    2016-02-01

    Full Text Available Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions.

  6. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie; Danquah, Agyemang; Zé licourt, Axel de; Hirt, Heribert; Colcombet, Jean

    2015-01-01

    rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests

  7. Stress activated MAPKs in plants

    NARCIS (Netherlands)

    Ligterink, J.W.

    2000-01-01

    Plants are exposed to a wide variety of extracellular stimuli and employ a broad set of signaling pathways to give the appropriate response. M itogen a ctivated p rotein k inases (MAPKs) play an important role in

  8. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie

    2015-08-27

    © 2015 Taylor & Francis Group, LLC. Abscisic acid (ABA) is a major phytohormone mediating important stress-related processes. We recently unveiled an ABA-activated MAPK signaling module constituted of MAP3K17/18-MKK3-MPK1/2/7/14. Unlike classical rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests that MAPKs can regulate both early and longterm plant stress responses.

  9. MAPK3 at the Autism-Linked Human 16p11.2 Locus Influences Precise Synaptic Target Selection at Drosophila Larval Neuromuscular Junctions.

    Science.gov (United States)

    Park, Sang Mee; Park, Hae Ryoun; Lee, Ji Hye

    2017-02-01

    Proper synaptic function in neural circuits requires precise pairings between correct pre- and post-synaptic partners. Errors in this process may underlie development of neuropsychiatric disorders, such as autism spectrum disorder (ASD). Development of ASD can be influenced by genetic factors, including copy number variations (CNVs). In this study, we focused on a CNV occurring at the 16p11.2 locus in the human genome and investigated potential defects in synaptic connectivity caused by reduced activities of genes located in this region at Drosophila larval neuromuscular junctions, a well-established model synapse with stereotypic synaptic structures. A mutation of rolled , a Drosophila homolog of human mitogen-activated protein kinase 3 ( MAPK3 ) at the 16p11.2 locus, caused ectopic innervation of axonal branches and their abnormal defasciculation. The specificity of these phenotypes was confirmed by expression of wild-type rolled in the mutant background. Albeit to a lesser extent, we also observed ectopic innervation patterns in mutants defective in Cdk2, Gα q , and Gp93, all of which were expected to interact with Rolled MAPK3. A further genetic analysis in double heterozygous combinations revealed a synergistic interaction between rolled and Gp93 . In addition, results from RT-qPCR analyses indicated consistently reduced rolled mRNA levels in Cdk2 , Gα q , and Gp93 mutants. Taken together, these data suggest a central role of MAPK3 in regulating the precise targeting of presynaptic axons to proper postsynaptic targets, a critical step that may be altered significantly in ASD.

  10. Chemical Aspects of Lesser Mouse Deer Meat

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    Djalal Rosyidi

    2012-02-01

    Full Text Available An experiment aiming for studying chemical aspects of lesser mouse deer meat (Tragulus javanicus. This research explored the chemical aspects of lesser mouse deer meat (Tragulus javanicus. Eight lesser mouse deer (four female and four male were used in chemical aspects of lesser mouse deer meat. The parameters observed included proximate analysis, amino acid, fatty acid, cholesterol and EPA-DHA of the meat. The results showed that average meat chemical composition were content of water, protein, fat, ash and cholesterol were 76.33 %, 21.42 %, 0.51 %, 1.20% and 50.00 mg/100 g, respectively. Fatty acid consist of lauric acid, miristate, palmitate, stearic, oleic, linoleic, and linolenic were 1.04 % 3.09%, 30.97, 0.77%., 59.41%, 3.22% and 1.12%, respectively. The total EPA and DHA was 0.13% and 0.05%,   Keywords: amino acid, fatty acid, cholesterol and EPA-DHA

  11. Isolated Displaced Fracture of the Lesser Tuberosity

    African Journals Online (AJOL)

    publication of this report. The authors declare no competing interests. Discussion. A delay in diagnosis of a lesser tuberosity fracture may lead to significant future clinical disability (2). In one such case the patient presented with axillary nerve neuropraxia while another case reported displacement of the biceps tendon (4).

  12. The avifauna of Flores (Lesser Sunda Islands)

    NARCIS (Netherlands)

    Mees, G.F.

    2006-01-01

    The avifauna of the island of Flores (Lesser Sunda Islands) is reviewed. Introductory sections, which include a chapter on the history of ornithological discovery, are followed by the main part, a systematic account in which each species and subspecies known from Flores is treated separately. A

  13. Herder and Modernity: From Lesser-Taught Languages to Lesser-Taught Cultures

    Directory of Open Access Journals (Sweden)

    Martin Votruba

    2017-03-01

    Full Text Available The typical North American curriculum of a lesser-taught Slavic language implicitly relies on the legacy of Johann Gottfried von Herder’s interpretation that language in and of itself contains national (ethnic culture. At the same time, enrolments are dwindling even in courses in the most commonly taught Slavic languages. Millennials’ understandable focus on the practicality of the courses they take make it unlikely for the lesser-taught languages to survive the slump. On the other hand, foreign culture courses are appearing to hold their ground more successfully. Slavic departments may reconsider Herder’s dictum as they try to maintain or establish programs in lesser-taught languages and cultures.

  14. Distribution of the early larval stages of cod, plaice and lesser sandeel across haline fronts in the North Sea

    DEFF Research Database (Denmark)

    Munk, Peter; Wright, P.J.; Pihl, Niels Jørgen

    2002-01-01

    A number of commercially important fish species spawn in the coastal areas of the North Sea in the late winter, including cod (Gadus morhua), plaice (Pleuronectes platessa) and lesser sandeel (Ammodytes marinus). The distribution of the early stages of these species overlap to some extent...... Influence (ROFI), predominantly in the Dogger Bank and German Bight areas. There was a high degree of overlap between the distributions of cod and plaice, while the maximal abundance of lesser sandeel was found inshore of the other species. Larval distributions were to a large extent confined by the frontal...

  15. Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells

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    Jan Kučera

    2017-01-01

    Full Text Available Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1 is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES cell maintenance. We employed wild-type and HIF-1α-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected. Downregulation of ERK could not be mimicked either by pharmacologically induced hypoxia or by the overexpression. Dual-specificity phosphatases (DUSP 1, 5, and 6 are hypoxia-sensitive MAPK-specific phosphatases involved in ERK downregulation, and protein phosphatase 2A (PP2A regulates both ERK and Akt. However, combining multiple approaches, we revealed the limited significance of DUSPs and PP2A in the hypoxia-mediated attenuation of ERK signaling. Interestingly, we observed a decreased reactive oxygen species (ROS level in hypoxia and a similar phosphorylation pattern for ERK when the cells were supplemented with glutathione. Therefore, we suggest a potential role for the ROS-dependent attenuation of ERK signaling in hypoxia, without the involvement of HIF-1.

  16. Avoiding revenue loss due to 'lesser of' contract clauses.

    Science.gov (United States)

    Stodolak, Frederick; Gutierrez, Henry

    2014-08-01

    Finance managers seeking to avoid lost revenue attributable to lesser-of-charge-or-fixed-fee (lesser-of) clauses in their contracts should: Identify payer contracts that contain lesser-of clauses. Prepare lesser-of lost-revenue reports for non-bundled and bundled rates. For claims with covered charges below the bundled rate, identify service codes associated with the greatest proportion of total gross revenue and determine new, higher charge levels for those codes. Establish an approach for setting charges for non-bundled fee schedules to address lost-revenue-related issues. Incorporate changes into overall strategic or hospital zero-based pricing modeling and parameters.

  17. Back-thrusting in Lesser Himalaya: Evidences from magnetic fabric ...

    Indian Academy of Sciences (India)

    Back-thrusting in Lesser Himalaya: Evidences from magnetic fabric studies in parts of Almora crystalline zone, Kumaun Lesser Himalaya. Amar Agarwal, K K Agarwal, R Bali, Chandra Prakash and Gaurav Joshi. Supplementary data. Table S1. AMS data, representing mean of values from cores (N) collected from each site ...

  18. Conservation Reserve Program mitigates grassland loss in the lesser prairie-chicken range of Kansas

    Science.gov (United States)

    Haukos, David A.; Spencer, David; Hagen, Christian A.; Daniels, Melinda D.; Goodin, Doug

    2017-01-01

    Since the beginning of the 20th century, the overall occupied range of the lesser prairie-chicken (Tympanuchus pallidicinctus) has declined by 84% commensurate with population trends. Much of this decline has been attributed to the loss and fragmentation of native grasslands throughout the lesser prairie-chicken range. However, quantification of changes in land cover in the distribution of the lesser prairie-chicken is lacking. Our objectives were to (1) document changes in the areal extent and connectivity of grasslands in the identified lesser prairie-chicken range in Kansas, USA, (>60% of extant lesser prairie-chicken population) from the 1950s to 2013 using remotely sensed data and (2) assess the potential of the Conservation Reserve Program (U.S. Department of Agriculture Program converting cropland to permanent cover; CRP) to mitigate grassland loss. Digital land cover maps were generated on a decadal time step through spectral classification of LANDSAT images and visual analysis of aerial photographs (1950s and 1960s). Landscape composition and configuration were assessed using FRAGSTATS to compute a variety of landscape metrics measuring changes in the amount of grassland present as well as changes in the size and configuration of grassland patches. With the exception of a single regional portion of the range, nearly all of the grassland converted to cropland in the lesser prairie-chicken range of Kansas occurred prior to the 1950s. Prior to the implementation of CRP, the amount of grassland decreased 3.6% between the 1950s and 1985 from 18,455 km2 to 17,788 km2. Since 1985, the overall amount of grassland in the lesser prairie-chicken range has increased 11.9% to 19,898 km2 due to implementation of CRP, although the area of grassland decreased between 1994 and 2013 as CRP contracts were not renewed by landowners. Since 1986 grassland in Kansas became more connected and less fragmented in response to the CRP. While the CRP has been successful in

  19. Conservation Reserve Program mitigates grassland loss in the lesser prairie-chicken range of Kansas

    Directory of Open Access Journals (Sweden)

    David Spencer

    2017-01-01

    Full Text Available Since the beginning of the 20th century, the overall occupied range of the lesser prairie-chicken (Tympanuchus pallidicinctus has declined by 84% commensurate with population trends. Much of this decline has been attributed to the loss and fragmentation of native grasslands throughout the lesser prairie-chicken range. However, quantification of changes in land cover in the distribution of the lesser prairie-chicken is lacking. Our objectives were to (1 document changes in the areal extent and connectivity of grasslands in the identified lesser prairie-chicken range in Kansas, USA, (>60% of extant lesser prairie-chicken population from the 1950s to 2013 using remotely sensed data and (2 assess the potential of the Conservation Reserve Program (U.S. Department of Agriculture Program converting cropland to permanent cover; CRP to mitigate grassland loss. Digital land cover maps were generated on a decadal time step through spectral classification of LANDSAT images and visual analysis of aerial photographs (1950s and 1960s. Landscape composition and configuration were assessed using FRAGSTATS to compute a variety of landscape metrics measuring changes in the amount of grassland present as well as changes in the size and configuration of grassland patches. With the exception of a single regional portion of the range, nearly all of the grassland converted to cropland in the lesser prairie-chicken range of Kansas occurred prior to the 1950s. Prior to the implementation of CRP, the amount of grassland decreased 3.6% between the 1950s and 1985 from 18,455 km2 to 17,788 km2. Since 1985, the overall amount of grassland in the lesser prairie-chicken range has increased 11.9% to 19,898 km2 due to implementation of CRP, although the area of grassland decreased between 1994 and 2013 as CRP contracts were not renewed by landowners. Since 1986 grassland in Kansas became more connected and less fragmented in response to the CRP. While the CRP has been successful

  20. Deformation mechanisms in the frontal Lesser Himalayan Duplex in ...

    Indian Academy of Sciences (India)

    kinematics of the LHD is in the process of being worked out .... also played a major role in the deformation process as evident from .... mation occurred at shallow crustal levels within ..... deep structure of the outer and Lesser Himalaya, Jumoan.

  1. Allium hookeri , Thw. Enum. A lesser known terrestrial perennial ...

    African Journals Online (AJOL)

    A lesser known terrestrial perennial herb used as food and its ethnobotanical ... from the wilderness, for consumption and traditional healing of various ailments. ... plants, the lifestyles of the people are changed and they prefer 'junk foods'.

  2. Comparative nutritional evaluation of some lesser known non ...

    African Journals Online (AJOL)

    Comparative nutritional evaluation of some lesser known non leguminous browse ... Dry matter (DM), crude protein (CP), crude fibre (CF) and ash level of the ... to be useful to ruminants as dietary supplement to poor quality dry season feed ...

  3. Pit above the lesser tuberosity in axial view radiography.

    Science.gov (United States)

    Cho, Jae-Ho; Han, Kyeong-Jin; Lee, Doo-Hyung; Chung, Nam-Su; Park, Do Young

    2015-02-01

    This study examined the relationship between the presence of a pit above the lesser tuberosity on axial view radiographs and rotator cuff tears and compared the demographic data between groups according to the presence of a pit above the lesser tuberosity. The hypothesis of this study was that the radiographic finding of a pit above the lesser tuberosity is related to rotator cuff tears. For 112 patients with a symptomatic rotator cuff tear, plain radiographs of the symptomatic shoulder (tear side radiographs) and plain radiographs of the asymptomatic contralateral shoulder (no-tear side radiographs) were assessed. Seventeen radiological findings, including a pit above the lesser tuberosity, osteophytes, subchondral cysts, and sclerosis, were recorded by one blinded observer. Demographic data such as age, duration of symptoms, sex, arm dominance, smoking history, trauma history, American Shoulder and Elbow Surgeons score, Constant score, and involved tendon were collected. A pit above the lesser tuberosity was noted on tear side radiographs of 40 patients (35.7 %) and on the no-tear side radiographs of 27 patients (24.1 %), representing a significant difference (P = 0.040). A pit associated with a rotator cuff tear was observed more often in the dominant arm (P = 0.040) and more often in patients with less previous trauma (P = 0.024). A pit above the lesser tuberosity on axial view radiography was associated with a rotator cuff tear and occurred more often in the dominant arm of patients who had no trauma history. Prognostic study, Level III.

  4. Primary small cell carcinoma of the lesser omentum

    Directory of Open Access Journals (Sweden)

    Ji-Feng Feng

    2012-02-01

    Full Text Available Although pulmonary small cell carcinoma (SCC is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.

  5. Rangewide genetic analysis of Lesser Prairie-Chicken reveals population structure, range expansion, and possible introgression

    Science.gov (United States)

    Oyler-McCance, Sara J.; DeYoung, Randall W; Fike, Jennifer; Hagen, Christian A.; Johnson, Jeff A.; Larsson, Lena C.; Patten, Michael

    2016-01-01

    The distribution of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) has been markedly reduced due to loss and fragmentation of habitat. Portions of the historical range, however, have been recolonized and even expanded due to planting of conservation reserve program (CRP) fields that provide favorable vegetation structure for Lesser Prairie-Chickens. The source population(s) feeding the range expansion is unknown, yet has resulted in overlap between Lesser and Greater Prairie-Chickens (T. cupido) increasing the potential for hybridization. Our objectives were to characterize connectivity and genetic diversity among populations, identify source population(s) of recent range expansion, and examine hybridization with the Greater Prairie-Chicken. We analyzed 640 samples from across the range using 13 microsatellites. We identified three to four populations corresponding largely to ecoregions. The Shinnery Oak Prairie and Sand Sagebrush Prairie represented genetically distinct populations (F ST > 0.034 and F ST > 0.023 respectively). The Shortgrass/CRP Mosaic and Mixed Grass ecoregions appeared admixed (F ST = 0.009). Genetic diversity was similar among ecoregions and N e ranged from 142 (95 % CI 99–236) for the Shortgrass/CRP Mosaic to 296 (95 % CI 233–396) in the Mixed Grass Prairie. No recent migration was detected among ecoregions, except asymmetric dispersal from both the Mixed Grass Prairie and to a lesser extent the Sand Sagebrush Prairie north into adjacent Shortgrass/CRP Mosaic (m = 0.207, 95 % CI 0.116–0.298, m = 0.097, 95 % CI 0.010–0.183, respectively). Indices investigating potential hybridization in the Shortgrass/CRP Mosaic revealed that six of the 13 individuals with hybrid phenotypes were significantly admixed suggesting hybridization. Continued monitoring of diversity within and among ecoregions is warranted as are actions promoting genetic connectivity and range expansion.

  6. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

    Directory of Open Access Journals (Sweden)

    Salvadore Christopher

    2004-09-01

    Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

  7. Vaccine-induced canine distemper in a lesser panda.

    Science.gov (United States)

    Bush, M; Montali, R J; Brownstein, D; James, A E; Appel, M J

    1976-11-01

    A fatal disease occurred in a lesser panda (Ailurus fulgens) 2 weeks after vaccination with modified live distemper vaccine. The disease clinically resembled canine distemper. Pathologically there was giant cell pneumonia, with canine distemper viral inclusion bodies in pulmonary and digestive tract epithelium. Viral isolates were indicative of an attenuated strain rather than virulent types.

  8. Nutrient Content of Four Lesser – Known Green Leafy Vegetables ...

    African Journals Online (AJOL)

    Leaves of four lesser – known leafy vegetable species (Heinsiacrinita, Lasiantheraafricana, Colocasiaesculenta and Ipomeabatatas) used for traditional food preparations by the Efik and Ibibio ethnic groups in Nigeria were analyzed for proximate composition, amino acid profile and mineral contents. The leaves were ...

  9. Migration flyway of the Mediterranean breeding Lesser Crested Tern ...

    African Journals Online (AJOL)

    The Lesser Crested Tern Thalasseus bengalensis emigratus breeding population in the Mediterranean is found exclusively in Libya, on the two coastal islands of Gara and Elba and one wetland on the mainland coast at Benghazi. In order to improve knowledge of the species migration to wintering quarters in West Africa, ...

  10. An amateur botanist on the Lesser Sunda Islands

    NARCIS (Netherlands)

    Schmutz, Erwin

    1976-01-01

    Tabula Rasa. In 1963 as a missionary I arrived in the Flora Malesiana region, notably in the Lesser Sunda Islands. A certain ’sensus botanicus’ was my only equipment for botanical surveys, and the next thing to do was to walk the arduous but occasionally quite entertaining road to discovery. I often

  11. Breeding of Greater and Lesser Flamingos at Sua Pan, Botswana ...

    African Journals Online (AJOL)

    to fledging was unknown owing to the rapid drying of the pan in late March 1999. No Greater Flamingo breeding was seen that season. Exceptional flooding during 1999–2000 produced highly favourable breeding conditions, with numbers of Greater and Lesser Flamingos breeding estimated to be 23 869 and 64 287 pairs, ...

  12. Sex determination in the Lesser Flamingo ( Phoenicopterus minor ...

    African Journals Online (AJOL)

    PCR amplification of the CHD-Z and CHD-W genes using DNA extracted from the blood samples was used to determine the sex of each bird. There were significant differences in mass and tarsus length among the three age groups, indicating that Lesser Flamingos continue to grow in skeletal size and mass between ...

  13. Evaluating indices of lipid and protein content in lesser snow and Ross's geese during spring migration

    Science.gov (United States)

    Webb, Elisabeth B.; Fowler, Drew N.; Woodall, Brendan A.; Vrtiska, Mark P.

    2018-01-01

    Assessing nutrient stores in avian species is important for understanding the extent to which body condition influences success or failure in life‐history events. We evaluated predictive models using morphometric characteristics to estimate total body lipids (TBL) and total body protein (TBP), based on traditional proximate analyses, in spring migrating lesser snow geese (Anser caerulescens caerulescens) and Ross's geese (A. rossii). We also compared performance of our lipid model with a previously derived predictive equation for TBL developed for nesting lesser snow geese. We used external and internal measurements on 612 lesser snow and 125 Ross's geese collected during spring migration in 2015 and 2016 within the Central and Mississippi flyways to derive and evaluate predictive models. Using a validation data set, our best performing lipid model for snow geese better predicted TBL (root mean square error [RMSE] of 23.56) compared with a model derived from nesting individuals (RMSE = 48.60), suggesting the importance of season‐specific models for accurate lipid estimation. Models that included body mass and abdominal fat deposit best predicted TBL determined by proximate analysis in both species (lesser snow goose, R2 = 0.87, RMSE = 23.56: Ross's geese, R2 = 0.89, RMSE = 13.75). Models incorporating a combination of external structural measurements in addition to internal muscle and body mass best predicted protein values (R2 = 0.85, RMSE = 19.39 and R2 = 0.85, RMSE = 7.65, lesser snow and Ross's geese, respectively), but protein models including only body mass and body size were also competitive and provided extended utility to our equations for field applications. Therefore, our models indicated the importance of specimen dissection and measurement of the abdominal fat pad to provide the most accurate lipid estimates and provide alternative dissection‐free methods for estimating protein.

  14. Evaluation of tsunami risk in the Lesser Antilles

    Directory of Open Access Journals (Sweden)

    N. Zahibo

    2001-01-01

    Full Text Available The main goal of this study is to give the preliminary estimates of the tsunami risks for the Lesser Antilles. We investigated the available data of the tsunamis in the French West Indies using the historical data and catalogue of the tsunamis in the Lesser Antilles. In total, twenty-four (24 tsunamis were recorded in this area for last 400 years; sixteen (16 events of the seismic origin, five (5 events of volcanic origin and three (3 events of unknown source. Most of the tsunamigenic earthquakes (13 occurred in the Caribbean, and three tsunamis were generated during far away earthquakes (near the coasts of Portugal and Costa Rica. The estimates of tsunami risk are based on a preliminary analysis of the seismicity of the Caribbean area and the historical data of tsunamis. In particular, we investigate the occurrence of historical extreme runup tsunami data on Guadeloupe, and these data are revised after a survey in Guadeloupe.

  15. A non-Mendelian MAPK-generated hereditary unit controlled by a second MAPK pathway in Podospora anserina.

    Science.gov (United States)

    Lalucque, Hervé; Malagnac, Fabienne; Brun, Sylvain; Kicka, Sébastien; Silar, Philippe

    2012-06-01

    The Podospora anserina PaMpk1 MAP kinase (MAPK) signaling pathway can generate a cytoplasmic and infectious element resembling prions. When present in the cells, this C element causes the crippled growth (CG) cell degeneration. CG results from the inappropriate autocatalytic activation of the PaMpk1 MAPK pathway during growth, whereas this cascade normally signals stationary phase. Little is known about the control of such prion-like hereditary units involved in regulatory inheritance. Here, we show that another MAPK pathway, PaMpk2, is crucial at every stage of the fungus life cycle, in particular those controlled by PaMpk1 during stationary phase, which includes the generation of C. Inactivation of the third P. anserina MAPK pathway, PaMpk3, has no effect on the development of the fungus. Mutants of MAPK, MAPK kinase, and MAPK kinase kinase of the PaMpk2 pathway are unable to present CG. This inability likely relies upon an incorrect activation of PaMpk1, although this MAPK is normally phosphorylated in the mutants. In PaMpk2 null mutants, hyphae are abnormal and PaMpk1 is mislocalized. Correspondingly, stationary phase differentiations controlled by PaMpk1 are defective in the mutants of the PaMpk2 cascade. Constitutive activation of the PaMpk2 pathway mimics in many ways its inactivation, including an effect on PaMpk1 localization. Analysis of double and triple mutants inactivated for two or all three MAPK genes undercover new growth and differentiation phenotypes, suggesting overlapping roles. Our data underscore the complex regulation of a prion-like element in a model organism.

  16. Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

    KAUST Repository

    Felemban, Abrar

    2016-01-01

    -activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal

  17. Regional development of districts in the Lesser Poland Voivodship

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    Marcin Salamaga

    2013-11-01

    Full Text Available Purpose of the article: Regional development includes qualitative changes in economy (e.g. in production, investments, employment as well as qualitative changes (regarding the structure of economy and society, changes in the environment. The research of regional development is important and necessary in order to make appropriate decisions at the regional and local level. The main purpose of the article is comparative analysis of districts in the Lesser Poland Voivodship in the area of economic, social and ecological development. Scientific aim: The scientific aims of paper are verifying the hypothesis concerning eco-development and forecasting the level of regional development in districts of Lesser Poland Voivodship. Methodology/methods: In the research of regional development the quality index of economic, social and ecological development has been proposed which has been calculated on the basis of a certain aggregation of the results of the Principal Component Analysis made on the correlation matrix of standardised variables being the components of the index. Forecasts of the regional development level in districts were calculated with the use of different econometric models as linear model, exponential model, or power model. Findings: The findings prove that the Lesser Poland Voivodship is characterised by considerable disproportions in regional development. The most favourable conditions for economic and social development are in the districts with large city agglomerations as well as extensive municipality infrastructure and transport infrastructure. The presented results demonstrate that the majority of districts have not exhibited a constant tendency to changes in the positions in successive ranking lists in terms of the economic, social and ecological development. The positions occupied by most districts are generally stable and have not changed considerably in the examined period. Conclusions: The research has confirmed the negative

  18. [DESIGN AND CLINICAL APPLICATION OF LESSER TROCHANTERIC REDUCTION FIXATION SYSTEM].

    Science.gov (United States)

    Guo, Xiaoze; Zhang, Ying; Xiao, Jin; Xie, Huibin; Yu, Jiefeng

    2015-02-01

    To design and produce a lesser trochanteric reduction fixation system and verify its value and effectiveness. A lesser trochanteric reduction fixation system was designed and produced according to the anatomical features of the lesser trochanteric fractures. Sixty-six patients with intertrochanteric fractures of Evans type III were included between January 2010 and July 2012. Of 66 patients, 32 were treated with dynamic hip screw (DHS) assisted with the lesser trochanteric reduction fixation system (study group), and 34 cases were treated with DHS only (control group). The 2 groups were comparable with no significant difference in gender, age, the reasons, and the types of the fractures (P > 0.05). The operation time, intraoperative blood loss, neck-shaft angle, bone healing time, ratio of successful fixations, and the functional evaluation of the hip joint after operation were compared between 2 groups. The study group had shorter operation time [(58.4 ± 5.3) minutes] and less intraoperative blood loss [(186.3 ± 6.6) mL than the control group [(78.5 ± 6.2)minutes and (246.2 ± 8.7) mL], showing significant differences (t = -14.040, P = 0.000; t = -31.145, P = 0.000). There was no significant difference in neck-shaft angle between study group [(138.6 ± 3.0)] and control group [(139.4 ± 2.9) degrees] (t = -1.044, P = 0.301). The wounds healed by first intention in both groups. The 30 and 31 patients were followed up 12 to 24 months (mean, 15 months) in the study group, and 13 to 25 months (mean, 16 months) in the control group, respectively. All fractures healed well in 2 groups. The study group had significantly shorter healing time [(8.8 ± 2.0) weeks] than the control group [(10.7 ± 3.4) weeks] (t = -2.871, P = 0.006). At 12 months after operation, coxa vara happened in 2 cases of the study group with a successful fixation ratio of 93.3% and in 10 cases of the control group with a successful fixation ratio of 67.7%, showing significant difference (Χ2 = 6

  19. Functional analysis of the MAPK pathways in fungi.

    Science.gov (United States)

    Martínez-Soto, Domingo; Ruiz-Herrera, José

    The Mitogen-Activated Protein Kinase (MAPK) signaling pathways constitute one of the most important and evolutionarily conserved mechanisms for the perception of extracellular information in all the eukaryotic organisms. The MAPK pathways are involved in the transfer to the cell of the information perceived from extracellular stimuli, with the final outcome of activation of different transcription factors that regulate gene expression in response to them. In all species of fungi, the MAPK pathways have important roles in their physiology and development; e.g. cell cycle control, mating, morphogenesis, response to different stresses, resistance to UV radiation and to temperature changes, cell wall assembly and integrity, degradation of cellular organelles, virulence, cell-cell signaling, fungus-plant interaction, and response to damage-associated molecular patterns (DAMPs). Considering the importance of the phylogenetically conserved MAPK pathways in fungi, an updated review of the knowledge on them is discussed in this article. This information reveals their importance, their distribution in fungal species evolutionarily distant and with different lifestyles, their organization and function, and the interactions occurring between different MAPK pathways, and with other signaling pathways, for the regulation of the most complex cellular processes. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Valuation issues in lesser developed countries: Investment opportunities

    International Nuclear Information System (INIS)

    Clements, P.J.

    1992-01-01

    Privatization has become the buzzword of the early 1990s, as all over the world governments are selling off their assets. Monopolistic utilities such as gas, water and waste disposal - but particularly electric - are prime assets for sale because their cash flows and competitive environment are reasonably predictable. Utility privatization in lesser developed countries (LDC) is giving rise to many new investment opportunities where predictions of high growth rates lead to anticipation of lucrative returns. Potential investors, however, should fully exercise the concept of caveat emptor: let the buyer beware. Coupled with these lucrative returns are risks arising from less stable political and economic conditions. possible market inefficiencies, and potentially high transaction costs. This article explores the central issues involved in valuing privatization investment opportunities in LDCs and performing requisite due diligence reviews

  1. Muon tomography: Plans for observations in the Lesser Antilles

    International Nuclear Information System (INIS)

    Gibert, Dominique; Beauducel, Francois; Lesparre, Nolwenn; Tarantola, Albert; Declais, Yves; Marteau, Jacques; Nicollin, Florence

    2010-01-01

    The application of muon tomography to monitor and image the internal structure of volcanoes in the Lesser Antilles is discussed. Particular focus is directed towards the three volcanoes that fall under the responsibility of the Institut de Physique du Globe of Paris, namely La Montagne Pelee in Martinique, La Soufriere in Guadeloupe, and the Soufriere Hills in Montserrat. The technological criteria for the design of portable muon telescopes are presented in detail for both their mechanical and electronic aspects. The detector matrices are constructed with scintillator strips, and their detection characteristics are discussed. The tomography inversion is presented, and its distinctive characteristics are briefly discussed. Details are given on the implementation of muon tomography experiments on La Soufriere in Guadeloupe. (author)

  2. The difference in cultural curriculum: for a lesser (Physical Education

    Directory of Open Access Journals (Sweden)

    Hugo César Bueno Nunes

    2017-05-01

    Full Text Available The current time is contingent, plural, decentralized, free of old identities and permeated by the noise of voices that have never been heard. Inserted in such context, the school tries to overcome traces of the past and face the struggles of the present. Regarding physical education, the cultural curriculum seems to contribute with the new era mentality by questioning the hegemony of body practices and meanings of the privileged groups to promote the pedagogy of difference. This study analyzed the most important works on this proposal, identifying teaching principles and procedures that characterize it and submitted them to the confrontation with the notion of pure difference by Gilles Deleuze. The results indicate that the cultural curriculum takes the features of a lesser (physical education when it listens what the „different ones‟ have to say and pays attention to the cultural body repertoire that students can access

  3. Assessing storm surge hazard and impact of sea level rise in the Lesser Antilles case study of Martinique

    Science.gov (United States)

    Krien, Yann; Dudon, Bernard; Roger, Jean; Arnaud, Gael; Zahibo, Narcisse

    2017-09-01

    In the Lesser Antilles, coastal inundations from hurricane-induced storm surges pose a great threat to lives, properties and ecosystems. Assessing current and future storm surge hazards with sufficient spatial resolution is of primary interest to help coastal planners and decision makers develop mitigation and adaptation measures. Here, we use wave-current numerical models and statistical methods to investigate worst case scenarios and 100-year surge levels for the case study of Martinique under present climate or considering a potential sea level rise. Results confirm that the wave setup plays a major role in the Lesser Antilles, where the narrow island shelf impedes the piling-up of large amounts of wind-driven water on the shoreline during extreme events. The radiation stress gradients thus contribute significantly to the total surge - up to 100 % in some cases. The nonlinear interactions of sea level rise (SLR) with bathymetry and topography are generally found to be relatively small in Martinique but can reach several tens of centimeters in low-lying areas where the inundation extent is strongly enhanced compared to present conditions. These findings further emphasize the importance of waves for developing operational storm surge warning systems in the Lesser Antilles and encourage caution when using static methods to assess the impact of sea level rise on storm surge hazard.

  4. Sequence alignment reveals possible MAPK docking motifs on HIV proteins.

    Directory of Open Access Journals (Sweden)

    Perry Evans

    Full Text Available Over the course of HIV infection, virus replication is facilitated by the phosphorylation of HIV proteins by human ERK1 and ERK2 mitogen-activated protein kinases (MAPKs. MAPKs are known to phosphorylate their substrates by first binding with them at a docking site. Docking site interactions could be viable drug targets because the sequences guiding them are more specific than phosphorylation consensus sites. In this study we use multiple bioinformatics tools to discover candidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targeting docking sites with drugs. Using sequence alignments of HIV proteins of different subtypes, we show that MAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependent manner, but are absent from HIV Rev and appear on all HIV Nef strains. We revise the regular expressions of previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reduces the number of required basic amino acids in the standard docking motifs from two to one. The proposed patterns are shown to be consistent with in silico docking between ERK1 and the HIV matrix protein. The motif usage on HIV proteins is sufficiently different from human proteins in amino acid sequence similarity to allow for HIV specific targeting using small-molecule drugs.

  5. Upregulation of MAPK/Erk and PI3K/Akt pathways in ulcerative colitis-associated colon cancer.

    Science.gov (United States)

    Setia, Shruti; Nehru, Bimla; Sanyal, Sankar Nath

    2014-10-01

    An extracellular signal like a cytokine or chemokine, secreted in the inflammatory microenvironment can activate the mitogen activated protein kinase (MAPK) pathway by binding to a cytokine receptor tyrosine kinase, which further activates tyrosine kinases such as Janus Kinase-3 (Jak-3). This signal is transferred from Jak-3 to the DNA in the nucleus of the cell by a chain of kinases, ultimately activating extracellular receptor kinase (Erk/MAPK). The latter phosphorylates c-myc, an oncogene, which alters the levels and activities of many transcription factors leading to cell survival, proliferation and invasion. The oncogenic PI3K pathway plays a similar role by activating c-myc, leading to cell survival and proliferation. The present study explores the role of ulcerative colitis in colon cancer by investigating the activities of tyrosine kinase activated MAPK pathway and various components of the PI3K pathway including PI3K, PTEN, PDK1, GSK3β, Akt, mTOR, Wnt and β-catenin. This was done by western blot and fluorescent immunohistochemical analysis of the above-mentioned proteins. Also, the morphological and histological investigation of the colonic samples from various animal groups revealed significant alterations as compared to the control in both inflammatory as well as carcinogenic conditions. These effects were reduced to a large extent by the co-administration of celecoxib, a second-generation non-steroidal anti-inflammatory drug (NSAID). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Plasticity of the MAPK signaling network in response to mechanical stress

    NARCIS (Netherlands)

    Pereira, Andrea M; Tudor, Cicerone; Pouille, Philippe-Alexandre; Shekhar, Shashank; Kanger, Johannes S; Subramaniam, Vinod; Martín-Blanco, Enrique

    2014-01-01

    Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK) cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms

  7. p38gamma and p38delta mitogen activated protein kinases (MAPKs, new stars in the MAPK galaxy

    Directory of Open Access Journals (Sweden)

    Alejandra eEscós

    2016-04-01

    Full Text Available The protein kinases p38γ and p38δ belong to the p38 mitogen-activated protein kinase (MAPK family. p38MAPK signalling controls many cellular processes and is one of the most conserved mechanisms in eukaryotes for the cellular response to environmental stress and inflammation. Although p38γ and p38δ are widely expressed, it is likely that they perform specific functions in different tissues. Their involvement in human pathologies such as inflammation-related diseases or cancer is starting to be uncovered. In this article we give a general overview and highlight recent advances made in defining the functions of p38γ and p38δ, focusing in innate immunity and inflammation. We consider the potential of the pharmacological targeting of MAPK pathways to treat autoimmune and inflammatory diseases and cancer

  8. Modeling of Marine Natural Hazards in the Lesser Antilles

    Science.gov (United States)

    Zahibo, Narcisse; Nikolkina, Irina; Pelinovsky, Efim

    2010-05-01

    The Caribbean Sea countries are often affected by various marine natural hazards: hurricanes and cyclones, tsunamis and flooding. The historical data of marine natural hazards for the Lesser Antilles and specially, for Guadeloupe are presented briefly. Numerical simulation of several historical tsunamis in the Caribbean Sea (1755 Lisbon trans-Atlantic tsunami, 1867 Virgin Island earthquake tsunami, 2003 Montserrat volcano tsunami) are performed within the framework of the nonlinear-shallow theory. Numerical results demonstrate the importance of the real bathymetry variability with respect to the direction of propagation of tsunami wave and its characteristics. The prognostic tsunami wave height distribution along the Caribbean Coast is computed using various forms of seismic and hydrodynamics sources. These results are used to estimate the far-field potential for tsunami hazards at coastal locations in the Caribbean Sea. The nonlinear shallow-water theory is also applied to model storm surges induced by tropical cyclones, in particular, cyclones "Lilli" in 2002 and "Dean" in 2007. Obtained results are compared with observed data. The numerical models have been tested against known analytical solutions of the nonlinear shallow-water wave equations. Obtained results are described in details in [1-7]. References [1] N. Zahibo and E. Pelinovsky, Natural Hazards and Earth System Sciences, 1, 221 (2001). [2] N. Zahibo, E. Pelinovsky, A. Yalciner, A. Kurkin, A. Koselkov and A. Zaitsev, Oceanologica Acta, 26, 609 (2003). [3] N. Zahibo, E. Pelinovsky, A. Kurkin and A. Kozelkov, Science Tsunami Hazards. 21, 202 (2003). [4] E. Pelinovsky, N. Zahibo, P. Dunkley, M. Edmonds, R. Herd, T. Talipova, A. Kozelkov and I. Nikolkina, Science of Tsunami Hazards, 22, 44 (2004). [5] N. Zahibo, E. Pelinovsky, E. Okal, A. Yalciner, C. Kharif, T. Talipova and A. Kozelkov, Science of Tsunami Hazards, 23, 25 (2005). [6] N. Zahibo, E. Pelinovsky, T. Talipova, A. Rabinovich, A. Kurkin and I

  9. The lesser evil? Initiating a benzodiazepine prescription in general practice

    Science.gov (United States)

    Anthierens, Sibyl; Habraken, Hilde; Petrovic, Mirko; Christiaens, Thierry

    2007-01-01

    Objective Chronic benzodiazepine (BZD) use is widespread and linked with adverse effects. There is consensus concerning the importance of initiating BZD as a crucial moment. Nevertheless specific research in this field is lacking. This paper addresses the views of GPs on why they start prescribing BZDs to first-time users. Design Qualitative study with five focus groups analysed using a systematic content analysis. Setting Regions of Ghent and Brussels in Belgium. Subjects A total of 35 general practitioners. Main outcome measure The GPs’ perspective on their initiating of BZD prescribing. Results GPs reported that they are cautious in initiating BZD usage. At the same time, GPs feel overwhelmed by the psychosocial problems of their patients. They show empathy by prescribing. They feel in certain situations there are no other solutions and they experience BZDs as the lesser evil. They admit to resorting to BZDs because of time restraint and lack of alternatives. GPs do not perceive the addictive nature of BZD consumption as a problem with first-time users. GPs do not specifically mention patients’ demand as an element for starting. Conclusion The main concern of GPs is to help the patient. GPs should be aware of the addictive nature of BZD even in low doses and a non-pharmacological approach should be seen as the best first approach. If GPs decide to prescribe a BZD they should make plain to the patient that the medication is only a “temporary” solution with clear agreements with regard to medication withdrawal. PMID:18041658

  10. Noise propagation in two-step series MAPK cascade.

    Directory of Open Access Journals (Sweden)

    Venkata Dhananjaneyulu

    Full Text Available Series MAPK enzymatic cascades, ubiquitously found in signaling networks, act as signal amplifiers and play a key role in processing information during signal transduction in cells. In activated cascades, cell-to-cell variability or noise is bound to occur and thereby strongly affects the cellular response. Commonly used linearization method (LM applied to Langevin type stochastic model of the MAPK cascade fails to accurately predict intrinsic noise propagation in the cascade. We prove this by using extensive stochastic simulations for various ranges of biochemical parameters. This failure is due to the fact that the LM ignores the nonlinear effects on the noise. However, LM provides a good estimate of the extrinsic noise propagation. We show that the correct estimate of intrinsic noise propagation in signaling networks that contain at least one enzymatic step can be obtained only through stochastic simulations. Noise propagation in the cascade depends on the underlying biochemical parameters which are often unavailable. Based on a combination of global sensitivity analysis (GSA and stochastic simulations, we developed a systematic methodology to characterize noise propagation in the cascade. GSA predicts that noise propagation in MAPK cascade is sensitive to the total number of upstream enzyme molecules and the total number of molecules of the two substrates involved in the cascade. We argue that the general systematic approach proposed and demonstrated on MAPK cascade must accompany noise propagation studies in biological networks.

  11. p38 MAPK signaling in postnatal tendon growth and remodeling.

    Directory of Open Access Journals (Sweden)

    Andrew J Schwartz

    Full Text Available Tendon is a dynamic tissue whose structure and function is influenced by mechanical loading, but little is known about the fundamental mechanisms that regulate tendon growth and remodeling in vivo. Data from cultured tendon fibroblasts indicated that the p38 MAPK pathway plays an important role in tendon fibroblast proliferation and collagen synthesis in vitro. To gain greater insight into the mechanisms of tendon growth, and explore the role of p38 MAPK signaling in this process, we tested the hypotheses that inducing plantaris tendon growth through the ablation of the synergist Achilles tendon would result in rapid expansion of a neotendon matrix surrounding the original tendon, and that treatment with the p38 MAPK inhibitor SB203580 would prevent this growth. Rats were treated with vehicle or SB203580, and subjected to synergist ablation by bilateral tenectomy of the Achilles tendon. Changes in histological and biochemical properties of plantaris tendons were analyzed 3, 7, or 28 days after overload, and comparisons were made to non-overloaded animals. By 28 days after overload, tendon mass had increased by 30% compared to non-overloaded samples, and cross-sectional area (CSA increased by around 50%, with most of the change occurring in the neotendon. The expansion in CSA initially occurred through the synthesis of a hyaluronic acid rich matrix that was progressively replaced with mature collagen. Pericytes were present in areas of active tendon growth, but never in the original tendon ECM. Inhibition of p38 MAPK resulted in a profound decrease in IL6 expression, and had a modest effect on the expression of other ECM and cell proliferation genes, but had a negligible impact on overall tendon growth. The combined results from this study provided novel insights into tendon mechanobiology, and suggest that p38 MAPK signaling does not appear to be necessary for tendon growth in vivo.

  12. Stratigraphy of the Grande Savane Ignimbrite Sequence, Dominica, Lesser Antilles

    Science.gov (United States)

    Schneider, S.; Smith, A. L.; Deuerling, K.; Killingsworth, N.; Daly, G.

    2007-12-01

    The island of Dominica, located in the central part of the Lesser Antilles island arc has eight potentially active volcanoes. One of these, Morne Diablotins, is a composite stratovolcano with several superimposed stratigraphic sequences ranging in age from Pliocene (4-2 Ma) to "Younger" Pleistocene (22,000 and >40,000 years B.P. The ignimbrite sequences form four flow fans that reached both the east and west coasts of the island. One of these flow fans, the Grande Savane, on the west coast of the island, also extends off-shore for a distance of at least 14 km as a distinctive submarine fan. Stratigraphical studies of the on- shore deposits that make up this fan indicate an older sequence of block and ash flow deposits, within which occurs a distinctive vulcanian fall deposit. These are overlain, with no evidence of an intervening paleosol, by a sequence of ignimbrites containing welded horizons (ranging in thickness from around 4 m to 16m). The lack of fall deposits beneath the ignimbrites suggest they may have been formed by instantaneous continuous collapse of the eruption column. This whole succession is overlain by a series of planar and dune bedded pumiceous surge deposits with interbedded pumiceous lapilli fall and ash fall deposits, that extend laterally outside of the main area of ignimbrite deposition. Beds within this upper sequence often contain accretionary lapilli and gas cavities suggesting magma-water interaction. The youngest deposits from Morne Diablotins appear to be valley- fill deposits of both ignimbrite and block and ash flow. A comparison of the of the Grande Savane pyroclastic sequence with the Pointe Ronde (west coast) and Londonderry (east coast) pyroclastic flow fans will provide information on the eruptive history of this major Plinian episode.

  13. Predictive MRI correlates of lesser metatarsophalangeal joint plantar plate tear

    Energy Technology Data Exchange (ETDEWEB)

    Umans, Rachel L. [Cornell University Medical College, New York, NY (United States); Umans, Benjamin D. [Harvard University, Cambridge, MA (United States); Umans, Hilary [Albert Einstein College of Medicine, Bronx, NY (United States); Lenox Hill Radiology and Imaging Associates, New York, NY (United States); Elsinger, Elisabeth [Albert Einstein College of Medicine, Bronx, NY (United States); Montefiore Medical Center, Bronx, NY (United States)

    2016-07-15

    To identify correlated signs on non-enhanced MRI that might improve diagnostic detection of plantar plate (PP) tear. We performed an IRB-approved, HIPAA-compliant retrospective analysis of 100 non-contrast MRI (50 PP tear, 50 controls). All were anonymized, randomized, and reviewed; 20 were duplicated to assess consistency. One musculoskeletal radiologist evaluated qualitative variables. A trained non-physician performed measurements. Consistency and concordance were assessed. Pearson's Chi-square test was used to test the correlation between qualitative findings and PP tear status. Correlation between measurements and PP status was assessed using t tests and Wilcoxon's rank-sum test (p values < 0.05 considered significant). Classification and regression trees were utilized to identify attributes that, taken together, would consistently distinguish PP tear from controls. Quantitative measurements were highly reproducible (concordance 0.88-0.99). Elevated 2nd MT protrusion, lesser MT supination and rotational divergence of >45 between the 1st-2nd MT axis correlated with PP tear. Pericapsular soft tissue thickening correlated most strongly with PP tear, correctly classifying 95 % of cases and controls. Excluding pericapsular soft tissue thickening, sequential assessment of 2nd toe enthesitis, 2nd flexor tendon subluxation, and splaying of the second and third toes accurately classified PP status in 92 %. Pericapsular soft tissue thickening most strongly correlated with PP tear. For cases in which it might be difficult to distinguish pericapsular fibrosis from neuroma, sequential assessment of 2nd toe enthesitis, flexor tendon subluxation and splaying of the 2nd and 3rd toe is most helpful for optimizing accurate diagnosis of PP tear. (orig.)

  14. Boron isotope ratios of surface waters in Guadeloupe, Lesser Antilles

    Energy Technology Data Exchange (ETDEWEB)

    Louvat, Pascale, E-mail: louvat@ipgp.fr [Geochimie et Cosmochimie, IPGP, Universite Paris Diderot, Sorbonne Paris Cite, UMR 7154 CNRS, 75005 Paris (France); Gaillardet, Jerome; Paris, Guillaume; Dessert, Celine [Geochimie et Cosmochimie, IPGP, Universite Paris Diderot, Sorbonne Paris Cite, UMR 7154 CNRS, 75005 Paris (France)

    2011-06-15

    Highlights: > Rivers outer of hydrothermal areas have d11B around 40 per mille and [B] of 10-31 {mu}g/L. > Thermal springs have d11B of 8-15 per mille and [B] between 250 and 1000 {mu}g/L. > With Na, SO{sub 4} and Cl, boron shows mixing of rain, low and high-T weathering inputs. > Guadeloupe rivers and thermal springs have d11B 20-40 per mille higher than the local rocks. > Solid-solution fractionation during weathering pathways may explain this gap of d11B. - Abstract: Large variations are reported in the B concentrations and isotopic ratios of river and thermal spring waters in Guadeloupe, Lesser Antilles. Rivers have {delta}{sup 11}B values around 40 per mille and B concentrations lower than 30 {mu}g/L, while thermal springs have {delta}{sup 11}B of 8-15 per mille and B concentrations of 250-1000 {mu}g/L. River samples strongly impacted by hydrothermal inputs have intermediate {delta}{sup 11}B and B contents. None of these surface water samples have {delta}{sup 11}B comparable to the local unweathered volcanic rocks (around 0 per mille), implying that a huge isotopic fractionation of 40 per mille takes place during rock weathering, which could be explained by preferential incorporation of {sup 10}B during secondary mineral formation and adsorption on clays, during rock weathering or in the soils. The soil-vegetation B cycle could also be a cause for such a fractionation. Atmospheric B with {delta}{sup 11}B of 45 per mille represents 25-95% of the river B content. The variety of the thermal spring chemical composition renders the understanding of B behavior in Guadeloupe hydrothermal system quite difficult. Complementary geochemical tracers would be helpful.

  15. Boron isotope ratios of surface waters in Guadeloupe, Lesser Antilles

    International Nuclear Information System (INIS)

    Louvat, Pascale; Gaillardet, Jerome; Paris, Guillaume; Dessert, Celine

    2011-01-01

    Highlights: → Rivers outer of hydrothermal areas have d11B around 40 per mille and [B] of 10-31 μg/L. → Thermal springs have d11B of 8-15 per mille and [B] between 250 and 1000 μg/L. → With Na, SO 4 and Cl, boron shows mixing of rain, low and high-T weathering inputs. → Guadeloupe rivers and thermal springs have d11B 20-40 per mille higher than the local rocks. → Solid-solution fractionation during weathering pathways may explain this gap of d11B. - Abstract: Large variations are reported in the B concentrations and isotopic ratios of river and thermal spring waters in Guadeloupe, Lesser Antilles. Rivers have δ 11 B values around 40 per mille and B concentrations lower than 30 μg/L, while thermal springs have δ 11 B of 8-15 per mille and B concentrations of 250-1000 μg/L. River samples strongly impacted by hydrothermal inputs have intermediate δ 11 B and B contents. None of these surface water samples have δ 11 B comparable to the local unweathered volcanic rocks (around 0 per mille), implying that a huge isotopic fractionation of 40 per mille takes place during rock weathering, which could be explained by preferential incorporation of 10 B during secondary mineral formation and adsorption on clays, during rock weathering or in the soils. The soil-vegetation B cycle could also be a cause for such a fractionation. Atmospheric B with δ 11 B of 45 per mille represents 25-95% of the river B content. The variety of the thermal spring chemical composition renders the understanding of B behavior in Guadeloupe hydrothermal system quite difficult. Complementary geochemical tracers would be helpful.

  16. Main copper-porphyry systems of the Lesser Caucasus

    International Nuclear Information System (INIS)

    Melkonyan, R.L.; Tayan, P.N.; Goukassyan, R.Kh.; Hovakimyan, S.E.; Moritz, R.; Selbi, D.

    2013-01-01

    Two belts of porphyry-copper systems were identified the Late Jurassic Early Cretaceous Somkheto-Karabakh (S-K) island-arc belt within the same name terrain of the southern termination of the Eurasian Plate stretching for 230 km (the tonalitic model) and the Early Miocene Tsaghkounk-Zanghezour (Ts-Z) post-collision belt (Tz-Z) within the same name terrain of the northern margin of the Gondwana, stretching over 280 km (the monzonite-granodiorite model). The formation of the S-K and Ts-Z belts had proceeded in pulses and spanned intervals of 12 million years and 24 million years, respectively. The Rb-Sr isochrones and TIMS U-Pb estimations of the age of zircons from the Meghri pluton ( 1,500 km 2 ), the largest one in the Lesser Caucasus, it appeared possible to establish the three stages of its formation: the Late Eocene, Early Oligocene, and Early Miocene, each accompanied by development of deposits having similar ages. The PC deposits of the S-K and Ts-Z belts have distinct differences of age, geodynamic regime of formation, specificity of mineral composition, sources of water and sulfur of hydrothermal solutions, and formation models. The single, discrete Armenian-Iranian belt of PC deposits was identified; it has a Late Eocene-Middle Miocene age and a length of about 2,000 km, being related with intrusive complexes of the monzonite-granite-granodiorite series, the activity of which had been manifesting itself over 32 million years. This belt, including giant-deposits such as Kajaran and Sar-Cheshmeh, was identified as the special Armenian-Iranian PC province

  17. Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer.

    Science.gov (United States)

    Slattery, Martha L; Lundgreen, Abbie; Wolff, Roger K

    2013-01-01

    Mitogen-activated protein kinase (MAPK) pathways regulate cellular functions including cell proliferation, differentiation, migration, and apoptosis. Associations between genes in the DUSP, ERK1/2, JNK, and p38 MAPK-signaling pathways and dietary factors associated with growth factors, inflammation, and oxidative stress and risk of colon and rectal cancer were evaluated. Data include colon cases (n = 1555) and controls (n = 1956) and rectal cases (n = 754) and controls (n = 959). Statistically significant interactions were observed for the MAPK-signaling pathways after adjustment for multiple comparisons. DUSP genes interacted with carbohydrates, mutagen index, calories, calcium, vitamin D, lycopene, dietary fats, folic acid, and selenium. MAPK1, MAPK3, MAPK1, and RAF1 within the ERK1/2 MAPK-signaling pathway interacted with dietary fats and cruciferous vegetables. Within the JNK MAPK-signaling pathway, interactions between MAP3K7 and protein, vitamin C, iron, folic acid, carbohydrates, and cruciferous vegetables; MAP3K10 and folic acid; MAP3K9 and lutein/zeaxanthin; MAPK8 and calcium; MAP3K3 and calcium and lutein; MAP3K1 and cruciferous vegetables. Interaction within the p38-signaling pathway included MAPK14 with calories, carbohydrates saturated fat, selenium, vitamin C; MAP3K2 and carbohydrates, and folic acid. These data suggest that dietary factors involved in inflammation and oxidative stress interact with MAPK-signaling genes to alter risk of colorectal cancer.

  18. Effects of Germline Mutations in the Ras/MAPK Signaling Pathway on Adaptive Behavior: Cardiofaciocutaneous Syndrome and Noonan Syndrome

    Science.gov (United States)

    Pierpont, Elizabeth I.; Pierpont, Mary Ella; Mendelsohn, Nancy J.; Roberts, Amy E.; Tworog-Dube, Erica; Rauen, Katherine A.; Seidenberg, Mark S.

    2011-01-01

    Cardiofaciocutaneous syndrome (CFC) and Noonan syndrome (NS) are two phenotypically overlapping genetic disorders whose underlying molecular etiologies affect a common signaling pathway. Mutations in the BRAF, MEK1 and MEK2 genes cause most cases of CFC and mutations in PTPN11, SOS1, KRAS and RAF1 typically cause NS. Although both syndromes are associated with developmental delays of varying severity, the extent to which the behavioral profiles differ may shed light on the different roles these respective genes play in development of skills necessary for everyday functioning. In this study, profiles of adaptive behavior of individuals with CFC and NS who had confirmed pathogenic mutations in Ras/MAPK pathway genes were investigated. Patterns of strengths and weaknesses, age-related differences, and risk factors for difficulties in adaptive skills were assessed. Although genes acting more downstream in the Ras/MAPK pathway were associated with more difficulties in adaptive functioning than genes more upstream in the pathway, several inconsistencies highlight the wide spectrum of possible developmental courses in CFC and NS. Along with clinical and genetic factors, variables such as chronological age, gestational age at birth and parental education levels accounted for significant variance in adaptive skills. Results indicate that there is wide heterogeneity in adaptive ability in CFC and NS, but that these abilities are correlated to some extent with the specific disease-causing genes. PMID:20186801

  19. Diabetes and male sex are key risk factor correlates of the extent of coronary artery calcification

    DEFF Research Database (Denmark)

    Nicoll, Rachel; Zhao, Ying; Wiklund, Urban

    2017-01-01

    for CAC scoring. RESULTS: Among all patients, male sex (OR = 4.85, pdyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension...... and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p... males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively. CONCLUSION: In addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes....

  20. ECR-MAPK regulation in liver early development.

    Science.gov (United States)

    Zhao, Xiu-Ju; Zhuo, Hexian

    2014-01-01

    Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week 16 of age. Meanwhile another independent animal experiment and cell culture were carried out for validation. Significance analysis of microarrays, qPCR verification, drug induction/inhibition assays, and metabonomics indicated that alpha-2u globulin (extracellular region)-socs2 (-SH2-containing signals/receptor tyrosine kinases)-ppp2r2a/pik3c3 (MAPK signaling)-hsd3b5/cav2 (metabolism/organization) plays a vital role in early development. Taken together, early development of male rats is ECR and MAPK-mediated coordination of cancer-like growth and negative regulations. Our data represent the first comprehensive description of early individual development, which could be a valuable basis for understanding the functioning of the gene interaction network of infant development.

  1. ECR-MAPK Regulation in Liver Early Development

    Directory of Open Access Journals (Sweden)

    Xiu-Ju Zhao

    2014-01-01

    Full Text Available Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week 16 of age. Meanwhile another independent animal experiment and cell culture were carried out for validation. Significance analysis of microarrays, qPCR verification, drug induction/inhibition assays, and metabonomics indicated that alpha-2u globulin (extracellular region-socs2 (-SH2-containing signals/receptor tyrosine kinases-ppp2r2a/pik3c3 (MAPK signaling-hsd3b5/cav2 (metabolism/organization plays a vital role in early development. Taken together, early development of male rats is ECR and MAPK-mediated coordination of cancer-like growth and negative regulations. Our data represent the first comprehensive description of early individual development, which could be a valuable basis for understanding the functioning of the gene interaction network of infant development.

  2. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

    International Nuclear Information System (INIS)

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit; Sil, Parames C.

    2009-01-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As

  3. Evidence for the Involvement of p38 MAPK Activation in Barnacle Larval Settlement

    KAUST Repository

    He, Li-Sheng

    2012-10-24

    The barnacle Balanus ( = Amphibalanus) amphitrite is a major marine fouling animal. Understanding the molecular mechanism of larval settlement in this species is critical for anti-fouling research. In this study, we cloned one isoform of p38 MAPK (Bar-p38 MAPK) from this species, which shares the significant characteristic of containing a TGY motif with other species such as yeast, Drosophila and humans. The activation of p38 MAPK was detected by an antibody that recognizes the conserved dual phosphorylation sites of TGY. The results showed that phospho-p38 MAPK (pp38 MAPK) was more highly expressed at the cyprid stage, particularly in aged cyprids, in comparison to other stages, including the nauplius and juvenile stages. Immunostaining showed that Bar-p38 MAPK and pp38 MAPK were mainly located at the cyprid antennules, and especially the third and fourth segments, which are responsible for substratum exploration during settlement. The expression and localization patterns of Bar-p38 MAPK suggest its involvement in larval settlement. This postulation was also supported by the larval settlement bioassay with the p38 MAPK inhibitor SB203580. Behavioral analysis by live imaging revealed that the larvae were still capable of exploring the surface of the substratum after SB203580 treatment. This shows that the effect of p38 MAPK on larval settlement might be by regulating the secretion of permanent proteinaceous substances. Furthermore, the level of pp38 MAPK dramatically decreased after full settlement, suggesting that Bar-p38 MAPK maybe plays a role in larval settlement rather than metamorphosis. Finally, we found that Bar-p38 MAPK was highly activated when larvae confronted extracts of adult barnacle containing settlement cues, whereas larvae pre-treated with SB203580 failed to respond to the crude adult extracts.

  4. Evidence for the Involvement of p38 MAPK Activation in Barnacle Larval Settlement

    KAUST Repository

    He, Li-Sheng; Xu, Ying; Matsumura, Kiyotaka; Zhang, Yu; Zhang, Gen; Qi, Shu-Hua; Qian, Pei-Yuan

    2012-01-01

    The barnacle Balanus ( = Amphibalanus) amphitrite is a major marine fouling animal. Understanding the molecular mechanism of larval settlement in this species is critical for anti-fouling research. In this study, we cloned one isoform of p38 MAPK (Bar-p38 MAPK) from this species, which shares the significant characteristic of containing a TGY motif with other species such as yeast, Drosophila and humans. The activation of p38 MAPK was detected by an antibody that recognizes the conserved dual phosphorylation sites of TGY. The results showed that phospho-p38 MAPK (pp38 MAPK) was more highly expressed at the cyprid stage, particularly in aged cyprids, in comparison to other stages, including the nauplius and juvenile stages. Immunostaining showed that Bar-p38 MAPK and pp38 MAPK were mainly located at the cyprid antennules, and especially the third and fourth segments, which are responsible for substratum exploration during settlement. The expression and localization patterns of Bar-p38 MAPK suggest its involvement in larval settlement. This postulation was also supported by the larval settlement bioassay with the p38 MAPK inhibitor SB203580. Behavioral analysis by live imaging revealed that the larvae were still capable of exploring the surface of the substratum after SB203580 treatment. This shows that the effect of p38 MAPK on larval settlement might be by regulating the secretion of permanent proteinaceous substances. Furthermore, the level of pp38 MAPK dramatically decreased after full settlement, suggesting that Bar-p38 MAPK maybe plays a role in larval settlement rather than metamorphosis. Finally, we found that Bar-p38 MAPK was highly activated when larvae confronted extracts of adult barnacle containing settlement cues, whereas larvae pre-treated with SB203580 failed to respond to the crude adult extracts.

  5. Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

    KAUST Repository

    Felemban, Abrar

    2016-05-01

    Stomata are cellular valves in plants that play an essential role in the regulation of gas exchange and are distributed in the epidermis of aerial organs. In Arabidopsis thaliana, stomatal production and development are coordinated by the mitogen-activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal development, by influencing the frequency at which stomata develop in leaves. This thesis presents an analysis of stomatal development in Arabidopsis mutants in two MAPK pathways: MEKK1-MKK1/MKK2-MPK4, and MAP3K17/18-MKK3. Obtained results demonstrate the effect of stress conditions on stomatal development and specify the involvement of analysed MAPK in stomatal patterning. First, both analysed pathways modulate stomatal patterning in Arabidopsis cotyledons. Second, plant growth-promoting bacteria tested enhance stomatal density and affect guard cell morphology. Third, the sucrose or mannitol treatment increases defects in stomatal patterning. Finally, salt stress or high temperature can suppress stomatal defects in mutants of the MEKK1-MKK1/MKK2-MPK4 pathway.

  6. Lesser Himalayan sequences in Eastern Himalaya and their deformation: Implications for Paleoproterozoic tectonic activity along the northern margin of India

    Directory of Open Access Journals (Sweden)

    Dilip Saha

    2013-05-01

    Full Text Available Substantial part of the northern margin of Indian plate is subducted beneath the Eurasian plate during the Caenozoic Himalayan orogeny, obscuring older tectonic events in the Lesser Himalaya known to host Proterozoic sedimentary successions and granitic bodies. Tectonostratigraphic units of the Proterozoic Lesser Himalayan sequence (LHS of Eastern Himalaya, namely the Daling Group in Sikkim and the Bomdila Group in Arunachal Pradesh, provide clues to the nature and extent of Proterozoic passive margin sedimentation, their involvement in pre-Himalayan orogeny and implications for supercontinent reconstruction. The Daling Group, consisting of flaggy quartzite, meta-greywacke and metapelite with minor mafic dyke and sill, and the overlying Buxa Formation with stromatolitic carbonate-quartzite-slate, represent shallow marine, passive margin platformal association. Similar lithostratigraphy and broad depositional framework, and available geochronological data from intrusive granites in Eastern Himalaya indicate strikewise continuity of a shallow marine Paleoproterozoic platformal sequence up to Arunachal Pradesh through Bhutan. Multiple fold sets and tectonic foliations in LHS formed during partial or complete closure of the sea/ocean along the northern margin of Paleoproterozoic India. Such deformation fabrics are absent in the upper Palaeozoic–Mesozoic Gondwana formations in the Lesser Himalaya of Darjeeling-Sikkim indicating influence of older orogeny. Kinematic analysis based on microstructure, and garnet composition suggest Paleoproterozoic deformation and metamorphism of LHS to be distinct from those associated with the foreland propagating thrust systems of the Caenozoic Himalayan collisional belt. Two possibilities are argued here: (1 the low greenschist facies domain in the LHS enveloped the amphibolite to granulite facies domains, which were later tectonically severed; (2 the older deformation and metamorphism relate to a Pacific type

  7. Observations on the activity patterns of the lesser yellow house bat ...

    African Journals Online (AJOL)

    lesser yellow house bat, Scotophilus viridis. F.P.D. Cotterill c/o Department of Zoology, University of Cape Town,. Cape Town. S.R. Giddings·. Department of Zoology, University of Pretoria, Pretoria,. 0002 Republic of South Africa. Received 10 June 1986; accepted 23 July 1986. The activity pattems of the lesser yellow ...

  8. Metatarsophalangeal joint stability: A systematic review on the plantar plate of the lesser toes

    NARCIS (Netherlands)

    Maas, N.M.G. (Nico M.G.); M. van der Grinten (Margot); W.M. Bramer (Wichor); G.J. Kleinrensink (Gert Jan)

    2016-01-01

    textabstractBackground: Instability of the metatarsophalangeal (MTP) joints of the lesser toes (digiti 2-5) is increasingly being treated by repair of the plantar plate (PP). This systematic review examines the anatomy of the plantar plate of the lesser toes, and the relation between the integrity

  9. Hepatic element concentrations of lesser scaup (aythya affinis) during spring migration in the upper midwest

    Science.gov (United States)

    Pillatzki, A.E.; Neiger, R.D.; Chipps, S.R.; Higgins, K.F.; Thiex, N.; Afton, A.D.

    2011-01-01

    High concentrations of some hepatic elements might be contributing to the decline of the continental lesser scaup (Aythya affinis) population. We evaluated hepatic element concentrations of male and female lesser scaup collected from the upper Midwest (Iowa, Minnesota, North Dakota, and South Dakota) during the 2003 and 2004 spring migrations. We measured concentrations of 24 elements in livers of 117 lesser scaup. We found that only selenium concentrations were at levels (>3.0 ??g/g wet weight [ww)]) proposed to adversely affect reproduction. Approximately 49% of females (n = 61) had individual hepatic concentrations >3.0 ??g/g ww selenium (Se). Our observed hepatic concentration of Se was similar to that reported in lesser scaup collected from the mid-continental United States but less than Se concentrations reported from the Great Lakes region. We found that the liver cadmium (Cd) concentration for males was significantly higher than that for females. Gender differences in hepatic Cd concentrations have not been previously reported for lesser scaup, but Cd is known to have negative impacts on male reproduction. Our results indicate that lesser scaup migrating through the upper Midwest in spring have elevated Se levels and that males carry a significantly greater Cd burden than females. Moreover, elemental concentrations might be high enough to affect reproduction in both male and female lesser scaup, but controlled laboratory studies are needed to adequately assess the effects of Se and Cd on lesser scaup reproduction. ?? 2010 Springer Science+Business Media, LLC.

  10. Why do lesser toes deviate laterally in hallux valgus? A radiographic study.

    Science.gov (United States)

    Roan, Li-Yi; Tanaka, Yasuhito; Taniguchi, Akira; Tomiwa, Kiyonori; Kumai, Tsukasa; Cheng, Yuh-Min

    2015-06-01

    Hallux valgus foot with laterally deviated lesser toes is a complex condition to treat. Ignoring the laterally deviated lesser toes in hallux valgus might result in unsatisfactory foot shape. Without lateral support of the lesser toes, it might increase the risk of recurrence of hallux valgus. We sought to identify associated radiographic findings in patients where lesser toes follow the great toe in hallux valgus and deviate laterally. The weight-bearing, anteroposterior foot radiographs of 24 female hallux valgus feet with laterally deviated lesser toes (group L), 34 female hallux valgus feet with normal lesser toes (group H), and 43 normal female feet (group N) were selected for the study. A 2-dimensional coordinated system was used to analyze the shapes and angles of these feet by converting each dot made on the radiographs onto X and Y coordinates. Diagrams of the feet in each group were drawn for comparison. The hallux valgus angle, lateral deviation angle of the second toe, intermetatarsal angles, toe length, metatarsal length, and metatarsus adductus were calculated according to the coordinates of the corresponding points. The mapping showed the bases of the second, third, and fourth toe in group L shifted laterally away from their corresponding metatarsal head (P hallux valgus angles (P hallux valgus angle, more adducted first metatarsal, and divergent lateral splaying of the lesser metatarsals were associated with lateral deviation of the lesser toes in hallux valgus. Level III, comparative study. © The Author(s) 2015.

  11. Active convergence between the Lesser and Greater Caucasus in Georgia: Constraints on the tectonic evolution of the Lesser-Greater Caucasus continental collision

    Science.gov (United States)

    Sokhadze, G.; Floyd, M.; Godoladze, T.; King, R.; Cowgill, E. S.; Javakhishvili, Z.; Hahubia, G.; Reilinger, R.

    2018-01-01

    We present and interpret newly determined site motions derived from GPS observations made from 2008 through 2016 in the Republic of Georgia, which constrain the rate and locus of active shortening in the Lesser-Greater Caucasus continental collision zone. Observation sites are located along two ∼160 km-long profiles crossing the Lesser-Greater Caucasus boundary zone: one crossing the Rioni Basin in western Georgia and the other crossing further east near the longitude of Tbilisi. Convergence across the Rioni Basin Profile occurs along the southern margin of the Greater Caucasus, near the surface trace of the north-dipping Main Caucasus Thrust Fault (MCTF) system, and is consistent with strain accumulation on the fault that generated the 1991 MW6.9 Racha earthquake. In contrast, convergence along the Tbilisi Profile occurs near Tbilisi and the northern boundary of the Lesser Caucasus (near the south-dipping Lesser Caucasus Thrust Fault), approximately 50-70 km south of the MCTF, which is inactive within the resolution of geodetic observations (< ± 0.5 mm/yr) at the location of the Tbilisi Profile. We suggest that the southward offset of convergence along strike of the range is related to the incipient collision of the Lesser-Greater Caucasus, and closing of the intervening Kura Basin, which is most advanced along this segment of the collision zone. The identification of active shortening near Tbilisi requires a reevaluation of seismic hazards in this area.

  12. Chk1 inhibition activates p53 through p38 MAPK in tetraploid cancer cells.

    Science.gov (United States)

    Vitale, Ilio; Senovilla, Laura; Galluzzi, Lorenzo; Criollo, Alfredo; Vivet, Sonia; Castedo, Maria; Kroemer, Guido

    2008-07-01

    We have previously shown that tetraploid cancer cells succumb through a p53-dependent apoptotic pathway when checkpoint kinase 1 (Chk1) is depleted by small interfering RNAs (siRNAs) or inhibited with 7-hydroxystaurosporine (UCN-01). Here, we demonstrate that Chk1 inhibition results in the activating phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Depletion of p38 MAPK by transfection with a siRNA targeting the alpha isoform of p38 MAPK (p38alpha MAPK) abolishes the phosphorylation of p53 on serines 15 and 46 that is induced by Chk1 knockdown. The siRNA-mediated downregulation and pharmacological inhibition of p38alpha MAPK (with SB 203580) also reduces cell death induced by Chk1 knockdown or UCN-01. These results underscore the role of p38 MAPK as a pro-apoptotic kinase in the p53-dependant pathway for the therapeutic elimination of polyploidy cells.

  13. Short duration small sided football and to a lesser extent whole body vibration exercise induce acute changes in markers of bone turnover

    DEFF Research Database (Denmark)

    Bowtell, Joanna L.; Jackman, Sarah R; Scott, Suzanne

    2016-01-01

    .8 ± 15.1 to 36.6 ± 14.7 μg·L(-1), P > 0.05). An increase in osteocalcin was observed 48 h after exercise (P type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0......) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6 ± 23.0 to 56.5 ± 22.5 μg·L(-1), mean ± SD, P

  14. Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover

    DEFF Research Database (Denmark)

    Bowtell, J. L.; Jackman, S. R.; Scott, S.

    2016-01-01

    We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60) sm...

  15. Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover

    Directory of Open Access Journals (Sweden)

    J. L. Bowtell

    2016-01-01

    Full Text Available We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n=56 were randomized to complete a single bout of short (FG15 or long duration (FG60 small sided football or low magnitude whole body vibration training (VIB. Procollagen type 1 amino-terminal propeptide (P1NP was increased during exercise for FG15 (51.6±23.0 to 56.5±22.5 μg·L−1, mean ± SD, P0.05. An increase in osteocalcin was observed 48 h after exercise (P<0.05, which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6±0.2 to 3.4±1.2 mM and FG60 (0.6±0.2 to 3.3±2.0 mM, but not for VIB (0.6±0.2 to 0.8±0.4 mM (P<0.05. Plasma creatine kinase increased by 55±63% and 137±119% 48 h after FG15 and FG60 (P<0.05, but not after VIB (26±54%, NS. In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health.

  16. Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ.

    Science.gov (United States)

    Kırça, M; Oğuz, N; Çetin, A; Uzuner, F; Yeşilkaya, A

    2017-04-01

    Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor β (PDGFRβ) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFRβ phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFRβ phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients.

  17. Avulsion of the Lesser Trochanter Following a Shot Put Sport Session

    Directory of Open Access Journals (Sweden)

    Mohamed H. Grissa

    2017-03-01

    Full Text Available Avulsion of the lesser trochanter is an uncommon injury. In children and adolescents it usually occurs as a sports injury via traumatic avulsion of the psoas major tendon. In adults, isolated fractures of the lesser trochanter are most commonly pathological due to metastatic tumor invasion of the proximal femur. This case report documents how a 14-year-old boy, who presented with an avulsion of the lesser trochanter of the proximal femur following a seemingly atraumatic shot put session at a track and field event, was diagnosed and successfully treated with a conservative approach.

  18. CT of the lesser pelvis - normal and abnormal anatomy, indications, results

    International Nuclear Information System (INIS)

    Steinbrich, W.; Friedmann, G.

    1981-01-01

    385 abnormal computer tomograms of the organs in the lesser pelvis were analysed; the normal anatomy, indications for CT and its value are discussed. Particular attention is paid to the relevance of the computer tomographic information for treatment. (orig.) [de

  19. 27 CFR 4.2 - Territorial extent.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Territorial extent. 4.2 Section 4.2 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.2 Territorial extent. This part...

  20. Diet composition of lesser kestrels in Ikh Nart Nature Reserve, Mongolia

    Directory of Open Access Journals (Sweden)

    Onolragchaa Ganbold

    2017-12-01

    Full Text Available The lesser kestrel is recognized as “Least Concern” in the International Union for Conservation of Nature (IUCN Red List since 2011. So far, all available diet studies on the lesser kestrel were conducted in its European range or in partial African breeding and nonbreeding range. In particular, little is known about the feeding behavior of this small falcon in Asian ranges. Thus, this study can be considered as the first to examine the diet composition of the central Asian breeding populations of lesser kestrels. This study aims to provide some information about the diet composition of this species among Asian populations through biological and ecological investigations. Pellets (n = 762 dropped by lesser kestrel (Falco naumanni were collected during their breeding season from nine to 10 colony sites in Ikh Nart, between June and September of 2009 and 2010, and analyzed. A total of 1,484 prey items were identified in the pellets collected. After a measure of their weight (g and length and width (mm, we carefully examined each pellet and separated all prey remains using tweezers. Our results indicated that insects (including orthopterans and coleopterans were dominant in lesser kestrel’s diets. We found that the lesser kestrel’s diet mainly consisted of insects (69.7%, lizards (17.4%, small mammals (10%, small birds (2%, and other food (1%. Keywords: diet composition, insects, pellets, reptiles, small mammals

  1. 78 FR 26302 - Endangered and Threatened Wildlife and Plants; Listing the Lesser Prairie-Chicken as a Threatened...

    Science.gov (United States)

    2013-05-06

    ...; 4500030113] RIN 1018-AY21 Endangered and Threatened Wildlife and Plants; Listing the Lesser Prairie-Chicken... the lesser prairie-chicken (Tympanuchus pallidicinctus). In addition, we announce the reopening of the public comment period on the December 11, 2012, proposed rule to list the lesser prairie-chicken as a...

  2. Genome-wide identification and expression analysis of MAPK and MAPKK gene family in Malus domestica.

    Science.gov (United States)

    Zhang, Shizhong; Xu, Ruirui; Luo, Xiaocui; Jiang, Zesheng; Shu, Huairui

    2013-12-01

    MAPK signal transduction modules play crucial roles in regulating many biological processes in plants, which are composed of three classes of hierarchically organized protein kinases, namely MAPKKKs, MAPKKs, and MAPKs. Although genome-wide analysis of this family has been carried out in some species, little is known about MAPK and MAPKK genes in apple (Malus domestica). In this study, a total of 26 putative apple MAPK genes (MdMPKs) and 9 putative apple MAPKK genes (MdMKKs) have been identified and located within the apple genome. Phylogenetic analysis revealed that MdMAPKs and MdMAPKKs could be divided into 4 subfamilies (groups A, B, C and D), respectively. The predicted MdMAPKs and MdMAPKKs were distributed across 13 out of 17 chromosomes with different densities. In addition, analysis of exon-intron junctions and of intron phase inside the predicted coding region of each candidate gene has revealed high levels of conservation within and between phylogenetic groups. According to the microarray and expressed sequence tag (EST) analysis, the different expression patterns indicate that they may play different roles during fruit development and rootstock-scion interaction process. Moreover, MAPK and MAPKK genes were performed expression profile analyses in different tissues (root, stem, leaf, flower and fruit), and all of the selected genes were expressed in at least one of the tissues tested, indicating that the MAPKs and MAPKKs are involved in various aspects of physiological and developmental processes of apple. To our knowledge, this is the first report of a genome-wide analysis of the apple MAPK and MAPKK gene family. This study provides valuable information for understanding the classification and putative functions of the MAPK signal in apple. © 2013.

  3. Impacts of mesquite distribution on seasonal space use of lesser prairie-chickens

    Science.gov (United States)

    Boggie, Matthew A.; Strong, Cody R.; Lusk, Daniel; Carleton, Scott A.; Gould, William R.; Howard, Randy L.; Nichols, Clay T.; Falkowski, Michael J.; Hagen, Christian A.

    2017-01-01

    Loss of native grasslands by anthropogenic disturbances has reduced availability and connectivity of habitat for many grassland species. A primary threat to contiguous grasslands is the encroachment of woody vegetation, which is spurred by disturbances that take on many forms from energy development, fire suppression, and grazing. These disturbances are exacerbated by natural- and human-driven cycles of changes in climate punctuated by drought and desertification conditions. Encroachment of honey mesquite (Prosopis glandulosa) into the prairies of southeastern New Mexico has potentially limited habitat for numerous grassland species, including lesser prairie-chickens (Tympanuchus pallidicinctus). To determine the magnitude of impacts of distribution of mesquite and how lesser prairie-chickens respond to mesquite presence on the landscape in southeastern New Mexico, we evaluated seasonal space use of lesser prairie-chickens in the breeding and nonbreeding seasons. We derived several remotely sensed spatial metrics to characterize the distribution of mesquite. We then used these data to create population-level resource utilization functions and predict intensity of use of lesser prairie-chickens across our study area. Home ranges were smaller in the breeding season compared with the nonbreeding season; however, habitat use was similar across seasons. During both seasons, lesser prairie-chickens used areas closer to leks and largely avoided areas with mesquite. Relative to the breeding season, during the nonbreeding season habitat use suggested a marginal increase in mesquite within areas of low intensity of use, yet aversion to mesquite was strong in areas of medium to high intensity of use. To our knowledge, our study is the first to demonstrate a negative behavioral response by lesser prairie-chickens to woody encroachment in native grasslands. To mitigate one of the possible limiting factors for lesser prairie-chickens, we suggest future conservation

  4. Radiologic measurement of lesser trochanter and its clinical significance in Chinese

    International Nuclear Information System (INIS)

    Zhang, Qi; Chen, Wei; Li, Xicheng; Song, Zhaohui; Pan, Jinshe; Zhang, Yingze; Liu, Huaijun

    2009-01-01

    Femoral fracture is a major cause of morbidity and mortality in elderly persons. Surgery, the main choice of treatment of femoral fracture, may result in some complications severely affecting patients' daily activities due to femoral malalignment. The lesser trochanter is an important anatomical structure of the femur which could be used as an anatomical landmark during and after operation to evaluate femoral alignment. To predict femoral rotational malalignment during surgery, the relationship between the height and width of the lesser trochanter and femoral rotation at different angles was investigated. Fifty healthy adult volunteers (25 men and 25 women) were enrolled in this study and a total of 900 radiographs of proximal femurs were taken in the following positions: neutral position, 5 , 10 , 15 , and 20 internal rotation, and 5 , 10 , 15 , and 20 external rotation, respectively. The cranio-caudal and transverse diameters of the lesser trochanter were obtained on a PACS Workstation. The height and width of the lesser trochanter increased with external rotation and decreased with internal rotation and the values showed statistical significance between different positions or different genders. Between 20 of internal rotation to 20 of external rotation, the mean height increased from 0.58 cm to 1.23 cm in men and from 0.44 cm to 1.19 cm in women. The corresponding mean values for width were from 2.53 cm to 4.44 cm in men, and from 2.08 cm to 3.86 cm in women, respectively. The height and width of the lesser trochanter were both highly correlated to the position of femur and the linear relationship was established approximately. The morphological alteration of lesser trochanter also changed obviously when the femurs rotated. The height and width of the lesser trochanter is linearly related to femoral rotation and could be used as a reference for prevention of femoral malalignment during surgery. (orig.)

  5. Lesser prairie-chicken avoidance of trees in a grassland landscape

    Science.gov (United States)

    Lautenbach, Joseph M.; Plumb, Reid T.; Robinson, Samantha G.; Hagen, Christian A.; Haukos, David A.; Pitman, James C.

    2016-01-01

    Grasslands are among the most imperiled ecosystems in North America. Reasons that grasslands are threatened include conversion to row-crop agriculture, fragmentation, and changes in fire regimes. The reduction of fire processes in remaining prairies has resulted in tree encroachment and establishment in grasslands, further reducing grassland quantity and quality. Grassland birds have been experiencing precipitous population declines in recent decades, commensurate with landscape changes to grasslands. The lesser prairie-chicken (Tympanuchus pallidicinctus Ridgway) is a declining species of prairie grouse of conservation concern. We used second- and third-order habitat selection metrics to test if female lesser prairie-chickens avoid grasslands where trees were present. Our results indicated that female lesser prairie-chickens selected habitats avoiding the nearest trees by 283 m on average, nearly twice as far as would be expected at random. Lesser prairie-chickens were 40 times more likely to use habitats with tree densities of 0 trees ∙ ha− 1 than habitats with 5 trees ∙ ha− 1. Probability of use indicated that lesser prairie-chickens were 19 times more likely to use habitats 1000 m from the nearest tree when compared with using habitats 0 m from the nearest tree. Nest survival was not affected at densities 2 trees ∙ ha− 1. Avoidance of trees could be due to perceived increased predation risk, reduced habitat quality, or a combination of these potentially confounding factors. Preventing further establishment and expansion of trees in landscapes occupied by lesser prairie-chickens could contribute to the continued persistence of the species. Additionally, restoring grasslands through tree removal may facilitate conservation efforts for grassland species such as the lesser prairie-chicken by improving habitat quality and promoting expansion of occupied range.

  6. DMPD: DUSP meet immunology: dual specificity MAPK phosphatases in control of theinflammatory response. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17114416 DUSP meet immunology: dual specificity MAPK phosphatases in control of the...ml) (.csml) Show DUSP meet immunology: dual specificity MAPK phosphatases in control of theinflammatory resp...onse. PubmedID 17114416 Title DUSP meet immunology: dual specificity MAPK phospha

  7. Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

    OpenAIRE

    Hsu, Hsin-Cheng; Tang, Nou-Ying; Liu, Chung-Hsiang; Hsieh, Ching-Liang

    2013-01-01

    Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA), which causes intracellular mitogen-activated protein kinase (MAPK) signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR) and rhynchophylline (RP) have anticonvulsive effects, although the mechanisms remain unclear. Therefore,...

  8. The value of CT in localizing primary and stomach-originated masses in the lesser sac

    International Nuclear Information System (INIS)

    Dong Peng; Wang Bin; Zhang Shizhuang; Chang Guanghui; Sun Xihe; Cheng Xin

    2007-01-01

    Objective: To investigate the normal CT manifestation of the vascular arch of the gastric lesser curvature, and to further probe the value of CT in the localization diagnosis of the primary and stomach-originated masses in the lesser sac. Methods: Contrast-enhanced CT scanning was performed in 51 normal individuals. Emphasis of image observation was focused on the CT manifestations of vascular arch of the gastric lesser curvature and the relation between the vascular arch and the gastric wall. Also contrast- enhanced CT scan was performed for seventeen cases of primary and stomach-originated masses in the lesser sac subsequently proved by surgery and pathology. Image analysis was focused on the relation between the mass and the vascular arch and its branches of the gastric lesser curvature, the shape of the mass, and the relation between the mass and the gastric wall. Results: The vascular arch of the gastric lesser curvature was clearly visualized in the fifty normal individuals. The tributaries of the vascular arch near the cardiac part, gastric corpus, and pyloric part were revealed in 42, 10 and 7 cases respectively. The vascular arch was in close contact with the gastric wall in 38 cases. Among the 17 patients, 13 cases demonstrated the obliteration of the transparent fat plane between the mass and the gastric wall. In 6 patients with stomach- originated masses, 5 patients showed the stretching of vascular arch tributaries adjacent to the masses, and no vascular arch and its tributaries could be not visualized between the masses and the stomach. In 11 patients with primary masses in the lesser sac, vascular arch were showed between the masses and the stomach in 10 cases, and no stretching of vascular arch tributaries adjacent to the masses could be showed. Conclusions: CT scan can clearly depict the normal vascular arch and its branches of the gastric lesser curvature. Based on the relation between the vascular arch and the gastric wall, the presence of fat

  9. Assessment of lesser prairie-chicken use of wildlife water guzzlers

    Science.gov (United States)

    Boal, Clint W.; Borsdorf, Philip K.; Gicklhorn, Trevor S.

    2014-01-01

    Man-made water sources have been used as a management tool for wildlife, especially in arid regions, but the value of these water sources for wildlife populations is not well understood. In particular, the value of water as a conservation tool for Lesser Prairie-Chickens (Tympanuchus pallidicinctus) is unknown. However, this is a relevant issue due to a heightened conservation concern for the species and its occupancy of an arid landscape anticipated to experience warmer, drier springs and winters. We assessed if Lesser Prairie-Chickens would use commercially available wildlife water guzzlers and if there was any apparent selection between two design types. We confirmed that Lesser Prairie-Chickens would use bird friendly designed wildlife water guzzlers. Use was primarily during the lekking-nesting period (March–May) and the brood rearing period (June–July) and primarily by males. Although both designs were used, we found significantly greater use of a design that had a wider water trough and ramp built into the tank cover compared to a design that had a longer, narrower trough extending from the tank.Although we were unable to assess the physiological need of surface water by Lesser Prairie-Chickens, we were able to verify that they will use wildlife water guzzlers to access surface water. If it is found surface water is beneficial for Lesser Prairie-Chickens, game bird friendly designed guzzlers may be a useful conservation tool for the species.

  10. Impact of MAPK Pathway Activation in BRAFV600 Melanoma on T Cell and Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Patrick A. Ott

    2013-10-01

    Full Text Available Constitutive upregulation of the MAPK pathway by a BRAFV600 mutation occurs in about half of melanomas. This leads to increased oncogenic properties such as tumor cell invasion, metastatic potential, and resistance to apoptosis. Blockade of the MAPK pathway with highly specific kinase inhibitors induces unprecedented tumor response rates in patients with advanced BRAFV600 mutant melanoma. Immune checkpoint blockade with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 and programed death-1/PD-L1 has also demonstrated striking anti-tumor activity in patients with advanced melanoma. Tumor responses are likely limited by multiple additional layers of immune suppression in the tumor microenvironment. There is emerging preclinical and clinical evidence suggesting that MAPK inhibition has a beneficial effect on the immunosuppressive tumor microenvironment, providing a strong rationale for combined immunotherapy and MAPK pathway inhibition in melanoma. The T cell response has been the main focus in the studies reported to date. Since dendritic cells (DCs are important in the induction of tumor-specific T cell responses, the impact of MAPK pathway activation in melanoma on DC function is critical for the melanoma directed immune response. BRAFV600E melanoma cells modulate DCs through the MAPK pathway because its blockade in melanoma cells can reverse suppression of DC function. As both MEK/BRAF inhibition and immune checkpoint blockade have recently taken center stage in the treatment of melanoma, a deeper understanding of how MAPK pathway inhibition affects the tumor immune response is needed.

  11. First complete genome sequence of parainfluenza virus 5 isolated from lesser panda.

    Science.gov (United States)

    Zhai, Jun-Qiong; Zhai, Shao-Lun; Lin, Tao; Liu, Jian-Kui; Wang, He-Xing; Li, Bing; Zhang, He; Zou, Shu-Zhan; Zhou, Xia; Wu, Meng-Fan; Chen, Wu; Luo, Man-Lin

    2017-05-01

    Parainfluenza virus 5 (PIV5) is widespread in mammals and humans. Up to now, there is little information about PIV5 infection in lesser pandas. In this study, a PIV5 variant (named ZJQ-221) was isolated from a lesser panda with respiratory disease in Guangzhou zoo in Guangdong province, southern China. The full-length genome of ZJQ-221 was found to be 15,246 nucleotides and consisted of seven non-overlapping genes encoding eight proteins (i.e., NP, V, P, M, F, SH, HN and L). Sequence alignment and genetic analysis revealed that ZJQ-221 shared a close relationship with a PIV5 strain of canine-origin (1168-1) from South Korea. The findings of this study confirm the presence of PIV5 in lesser panda and indicate this mammal as a possible natural reservoir. Furthermore they highlight the urgent need to strengthen viral surveillance and control of PIV5 in zoo animals.

  12. The effect of listing the lesser prairie chicken as a threatened species on rural property values.

    Science.gov (United States)

    Wietelman, Derek C; Melstrom, Richard T

    2017-04-15

    This paper estimates the effect of Endangered Species Act protections for the lesser prairie chicken (Tympanuchus pallidicinctus) on rural property values in Oklahoma. The political and legal controversy surrounding the listing of imperiled species raises questions about the development restrictions and opportunity costs the Endangered Species Act imposes on private landowners. Examining parcel-level sales data before and after the listing of the endemic lesser prairie chicken, we employ difference-in-differences (DD) regression to measure the welfare costs of these restrictions. While our basic DD regression provides evidence the listing was associated with a drop in property values, this finding does not hold up in models that control for latent county and year effects. The lack of a significant price effect is confirmed by several robustness checks. Thus, the local economic costs of listing the lesser prairie chicken under the Endangered Species Act appear to have been small. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Landscape composition creates a threshold influencing Lesser Prairie-Chicken population resilience to extreme drought

    Science.gov (United States)

    Ross, Beth E.; Haukos, David A.; Hagen, Christian A.; Pitman, James C.

    2016-01-01

    Habitat loss and degradation compound the effects of climate change on wildlife, yet responses to climate and land cover change are often quantified independently. The interaction between climate and land cover change could be intensified in the Great Plains region where grasslands are being converted to row-crop agriculture concurrent with increased frequency of extreme drought events. We quantified the combined effects of land cover and climate change on a species of conservation concern in the Great Plains, the Lesser Prairie-Chicken (Tympanuchus pallidicinctus  ). We combined extreme drought events and land cover change with lek count surveys in a Bayesian hierarchical model to quantify changes in abundance of male Lesser Prairie-Chickens from 1978 to 2014 in Kansas, the core of their species range. Our estimates of abundance indicate a gradually decreasing population through 2010 corresponding to drought events and reduced grassland areas. Decreases in Lesser Prairie-Chicken abundance were greatest in areas with increasing row-crop to grassland land cover ratio during extreme drought events, and decreased grassland reduces the resilience of Lesser Prairie-Chicken populations to extreme drought events. A threshold exists for Lesser Prairie-Chickens in response to the gradient of cropland:grassland land cover. When moving across the gradient of grassland to cropland, abundance initially increased in response to more cropland on the landscape, but declined in response to more cropland after the threshold (δ=0.096, or 9.6% cropland). Preservation of intact grasslands and continued implementation of initiatives to revert cropland to grassland should increase Lesser Prairie-Chicken resilience to extreme drought events due to climate change.

  14. Abnormal development of the lesser wing of the sphenoid with microphthalmos and microcephaly

    International Nuclear Information System (INIS)

    Jacquemin, C.; Bosley, T.M.

    2001-01-01

    We report two patients with abnormal development of the lesser wing of the sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the normal closure of the optic vesicle and normal growth of encephalic structures, possibly by disturbing developmental tissue interactions. These patients may exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular neurofibromas and other factors associated with that disease. (orig.)

  15. Lesser sac hematoma as a sign of rupture of hepatocellular carcinoma in the caudate lobe

    International Nuclear Information System (INIS)

    Iwasaki, Yoshie; Tani, Ichiro; Nakajima, Yasuo; Ishikawa, Tohru; Umeda, Satoshi; Kusano, Shoichi

    2001-01-01

    The purpose of this study was to evaluate the CT findings of rupture of hepatocellular carcinoma (HCC) in the caudate lobe of the liver. The CT scans of five cases of rupture of HCC in the caudate lobe of the liver were retrospectively reviewed and correlated with clinical records. All cases showed exophytic tumors in the caudate lobe of the liver and high-attenuation hematomas in the lesser sac on CT. A lesser sac hematoma may be a sentinel clot sign of rupture of HCC in the caudate lobe. (orig.)

  16. Digestibily of Some Kind of Alternative Diets on Lesser Mouse Deer (Tragulus javanicus

    Directory of Open Access Journals (Sweden)

    WR Farida

    2004-01-01

    Full Text Available Four female lesser mouse deer (Tragulus javanicus were used in this study to observe their feed consumption and digestibility given alternative diets in captive.  The results showed that 125g/head/day sweet potatoes supplementation in ration increased the consumption and digestibility of dry matter intake, ash, ether extract, and N-free extract. Supplementation of commercial concentrate in lesser mouse deer’s diet decreased the digestion of dry matter, ash, crude protein, and crude fiber. Animal Production 6(1: 17-22 (2004   Key Words: Digestibility, Consumption, Alternative Diets, Tragulus javanicus

  17. Abnormal development of the lesser wing of the sphenoid with microphthalmos and microcephaly

    Energy Technology Data Exchange (ETDEWEB)

    Jacquemin, C. [King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia). Radiology Dept.; Mullaney, P. [Paediatric Ophthalmology Div., King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia); Bosley, T.M. [Neuro-Ophthalmology Div., King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

    2001-02-01

    We report two patients with abnormal development of the lesser wing of the sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the normal closure of the optic vesicle and normal growth of encephalic structures, possibly by disturbing developmental tissue interactions. These patients may exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular neurofibromas and other factors associated with that disease. (orig.)

  18. Data on the phosphorylation of p38MAPK and JNK induced by chlorpyrifos in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    J.E.S. Batista

    2016-12-01

    Full Text Available Exposure to organophosphate compounds, such as chlorpyrifos, has been linked to disturbances on cell signaling pathways. Mitogen activated protein kinases (MAPK are a family of protein kinases involved in a range of cellular processes, including stress response, apoptosis and survival. Therefore, changes in the activation state of these kinases may characterize key mechanisms of toxicity elicited by xenobiotics. Here we report data on the phosphorylation of p38MAPK and JNK, members of the MAPK family, in Drosophila melanogaster exposed to chlorpyrifos, as characterized by western blotting assays.

  19. Ancient signals: comparative genomics of plant MAPK and MAPKK gene families

    DEFF Research Database (Denmark)

    Hamel, Louis-Philippe; Nicole, Marie-Claude; Sritubtim, Somrudee

    2006-01-01

    MAPK signal transduction modules play crucial roles in regulating many biological processes in plants, and their components are encoded by highly conserved genes. The recent availability of genome sequences for rice and poplar now makes it possible to examine how well the previously described...... Arabidopsis MAPK and MAPKK gene family structures represent the broader evolutionary situation in plants, and analysis of gene expression data for MPK and MKK genes in all three species allows further refinement of those families, based on functionality. The Arabidopsis MAPK nomenclature appears sufficiently...

  20. Updated Vertical Extent of Collision Damage

    DEFF Research Database (Denmark)

    Tagg, R.; Bartzis, P.; Papanikolaou, P.

    2002-01-01

    The probabilistic distribution of the vertical extent of collision damage is an important and somewhat controversial component of the proposed IMO harmonized damage stability regulations for cargo and passenger ships. The only pre-existing vertical distribution, currently used in the international...

  1. The Geographic Extent of Global Supply Chains

    DEFF Research Database (Denmark)

    Machikita, Tomohiro; Ueki, Yasushi

    2012-01-01

    We study the extent to which inter-firm relationships are locally concentrated and what determines firm differences in geographic proximity to domestic or foreign suppliers and customers. From micro-data on selfreported customer and supplier data of firms in Indonesia, the Philippines, Thailand, ...

  2. Long distance commutes by lesser long-nosed bats (Leptonycteris yerbabuenae) to visit residential hummingbird feeders

    Science.gov (United States)

    Debbie C. Buecher; Ronnie. Sidner

    2013-01-01

    Each spring, thousands of female lesser long-nosed bats (Leptonycteris yerbabuenae) migrate from southern Mexico to northern Sonora and southern Arizona to have their young and take advantage of seasonably available forage resources, including nectar, pollen, and fruit of columnar cacti. Once the pups are volant, the population begins to disperse across the grasslands...

  3. Physicochemical and Organoleptic Properties of Dried Synbiotics Yoghurt from Lesser Yam Tubers (Dioscoreaesculenta L.

    Directory of Open Access Journals (Sweden)

    Winarti Sri

    2016-01-01

    Full Text Available There are many variations of Yam (Dioscorea spp. which spread out in the world including Indonesia. Those variations could be categorized based on their shape, size, colour, and flavour of their tuber. The genus of Dioscorea spp. has more than 600 species, such as Dioscorea hispida, Dioscorea esculenta (lesser yam, Discorea bulbifera, Dioscorea alata (purple yam, Dioscorea opposita (white yam, Dioscorea villosa (yellow yam, Dioscorea altassima, and Dioscorea elephantipes. At the present, the utilization of yam tubers is seen to be limited. The purpose of the research was to evaluate the properties/characteristics of dried synbiotics yoghurt from lesser yam tubers. The treatment on this study was performed by the number of substitution of lesser yam tubers and the fermentation time. The results show that the dried synbiotics yoghurt that most preferred by consumers was G2F3 (lesser yam 40% and fermentation time 22 hours with an average value 3.65. It is followed by the total LAB (lactic acid bacteria 8,15 log cfu/g, pH 4.27, total lactic acid 1.02%, yield of dried synbiotic yoghurt 32.30%, and total soluble protein 4.53%.

  4. The Lesser Antillean Iguana on St. Eustatius: 2012 status update and review of limiting factors

    NARCIS (Netherlands)

    Debrot, A.O.; Boman, E.

    2013-01-01

    The endangered Lesser Antillean Iguana, Iguana delicatissima, is an emblematic species for the island of St. Eustatius and in Caribbean Netherlands it is only found on St. Eustatius. In this study we conducted an extensive population survey for the iguana and compared densities in different areas to

  5. European Economic Integration and the Fate of Lesser-Used Languages.

    Science.gov (United States)

    Grin, Francois

    1993-01-01

    The consequences of economic integration for Europe's lesser-used languages are examined. Applying theoretical predictions to a set of 12 minority languages, this paper shows that 5 will likely be in a more favorable position, 4 may lose as a result of economic integration, and no clear effect can be predicted for the remaining 3. (18 references)…

  6. Documenting Sociolinguistic Variation in Lesser-Studied Indigenous Communities: Challenges and Practical Solutions

    Science.gov (United States)

    Mansfield, John; Stanford, James

    2017-01-01

    Documenting sociolinguistic variation in lesser-studied languages presents methodological challenges, but also offers important research opportunities. In this paper we examine three key methodological challenges commonly faced by researchers who are outsiders to the community. We then present practical solutions for successful variationist…

  7. Theory of mind in children with 'lesser variants' of autism : a longitudinal study

    NARCIS (Netherlands)

    Serra, M; Loth, FL; van Geert, PLC; Hurkens, E; Minderaa, RB

    2002-01-01

    Background: The study investigated the development of theory-of-mind (ToM) knowledge in children with 'lesser variants' of autism (PDD-NOS) over a period thought to be critical for ToM development (i.e., 3 to 5 years of age). Method: The sample included 11 children with PDD-NOS; 23 normally

  8. First Evidence of Angiostrongyliasis Caused by Angiostrongylus cantonensis in Guadeloupe, Lesser Antilles

    Science.gov (United States)

    Dard, Céline; Piloquet, Jean-Eudes; Qvarnstrom, Yvonne; Fox, LeAnne M.; M'kada, Helmi; Hebert, Jean-Christophe; Mattera, Didier; Harrois, Dorothée

    2017-01-01

    Infection by the rat lungworm Angiostrongylus cantonensis represents the most common cause of infectious eosinophilic meningitis in humans, causing central nervous system (CNS) angiostrongyliasis. Most of CNS angiostrongyliasis cases were described in Asia, Pacific Basin, Australia, and some limited parts of Africa and America. CNS angiostrongyliasis has been reported in the Caribbean but never in the Lesser Antilles. The primary objectives of this study were to depict the first case of CNS angiostrongyliasis in the Lesser Antilles and investigate the environmental presence of A. cantonensis in Guadeloupe, Lesser Antilles. In December 2013, a suspected case of CNS angiostrongyliasis in an 8-month-old infant in Guadeloupe was investigated by real-time polymerase chain reaction (PCR) testing on cerebral spinal fluid (CSF). The environmental investigation was performed by collecting Achatina fulica molluscs from different parts of Guadeloupe and testing the occurrence of A. cantonensis by real-time PCR. CSF from the suspected case of angiostrongyliasis was positive for A. cantonensis by real-time PCR. Among 34 collected snails for environmental investigation, 32.4% were positive for A. cantonensis. In conclusion, we report the first laboratory-confirmed case of CNS-angiostrongyliasis in the Lesser Antilles. We identified the presence and high prevalence of A. cantonensis in A. fulica in Guadeloupe. These results highlight the need to increase awareness of this disease and implement public health programs in the region to prevent human cases of angiostrongyliasis and improve management of eosinophilic meningitis patients. PMID:28070007

  9. The Lesser Antillean Ameiva (Sauria, Teiidae) Re-evaluation, zoogeography and the effects of predation

    NARCIS (Netherlands)

    Baskin, Jonathan N.; Williams, Ernest E.

    1966-01-01

    The Ameiva of the Lesser Antilles present an interesting case of isolated populations of related animals on a chain of islands that differ in size and proximity among themselves but form a geographic group. The situation is made still more interesting by the fact that at times in the Pleistocene the

  10. Oxygen deficiency impacts on burying habitats for lesser sandeel, Ammodytes tobianus, in the inner Danish waters

    DEFF Research Database (Denmark)

    Behrens, Jane; Ærtebjerg, Gunni; Petersen, Jens Kjerulf

    2009-01-01

    Starting in 1980s, the inner Danish waters have yearly been exposed to seasonal oxygen deficiency (hypoxia). Through spatial–temporal interpolation of monitoring data (1998–2005), we investigated oxygen deficiency impacts on suitable burying habitats for lesser sandeel (Ammodytes tobianus...

  11. Radial variation in fiber length of some lesser used wood species in ...

    African Journals Online (AJOL)

    computer

    2012-09-20

    Sep 20, 2012 ... Variations in fibre length of ten lesser used wood species were investigated. The mean fibre length ..... the growth of coniferous trees. Can. J. Bot.45: 1359-1369 ... morphology and paper properties: a review of literature. Tappi ...

  12. A new subspecies of Accipiter virgatus (Temminck) from Flores, Lesser Sunda Islands, Indonesia (Aves: Accipitridae)

    NARCIS (Netherlands)

    Mees, G.F.

    1984-01-01

    A new subspecies of Accipiter virgatus (Temminck) is described from Flores (Lesser Sunda Islands). In addition some notes are given on the distribution of A. virgatus in south-eastern Burma and adjacent parts of Thailand, supplementary to an earlier paper (Mees, 1981).

  13. Radial variation in fiber length of some lesser used wood species in ...

    African Journals Online (AJOL)

    Variations in fibre length of ten lesser used wood species were investigated. The mean fibre length varied from 1.07mm in Lannea acida to 2.41mm in Sterculia setigera. Four patterns of within tree radial variations in fibre length were observed in the studied species. In pattern one, fibre length increased from the pith to the ...

  14. SUMO-, MAPK- and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    Burg, van den H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  15. SUMO-, MAPK-, and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    van den Burg, H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  16. The role of MAPK signaling in patterning and establishing axial symmetry in the gastropod Haliotis asinina

    DEFF Research Database (Denmark)

    Koop, Demian; Richards, Gemma S; Wanninger, Andreas

    2007-01-01

    , the embryo begins to gastrulate and assumes a bilateral cleavage pattern. Here we inhibit MAPK activation in 3D with U0126 and examine its effect on the formation and patterning of the trochophore, using a suite of territory-specific markers. The head (pretrochal) region appears to maintain quadri...... (D) quadrant is intimately linked with body plan organization and in equally cleaving gastropods occurs when one of the vegetal macromeres makes contact with overlying micromeres and receives an inductive signal that activates a MAPK signaling cascade. Following the induction of the 3D macromere......-radial symmetry in U0126-treated embryos, supporting a role for MAPK signaling in 3D in establishing dorsoventral polarity in this region. Posterior (posttrochal) structures - larval musculature, shell and foot--fail to develop in MAPK inhibited trochophores. Inhibition of 3D specification by an alternative...

  17. Variation in Crustal Structure of the Lesser Caucasus Region from Teleseismic Receiver Functions

    Science.gov (United States)

    Lin, C. M.; Tseng, T. L.; Huang, B. S.; Legendre, C. P.; Karakhanian, A.

    2016-12-01

    The Caucasus, including the mountains of Greater and Lesser Caucasus, is formed by the continental collision between Arabia and Eurasia. The crustal thickness for this region was mostly constrained by joint analysis of receiver functions and surface waves. Although the thickest value of 52 km was reported under the Lesser Caucasus, the resolution of earlier studies were often limited by sparse array. Large gradient across Moho also makes the definition of Moho difficult. Moreover, higher value of the Vp/Vs ratio is commonly reported in the northeastern Turkey but no estimates had been made for the Caucasus. To further investigate the detail structure around the Lesser Caucasus, we constructed a new seismic network in Georgia and Armenia. We also include other broadband stations to enhance the coverage. The average interval in the Lesser Caucasus is roughly 30 km, much denser than any previous experiments. We selected P-waveforms from teleseismic earthquakes during the operation (January 2012 - June 2016) to calculate receiver functions and then estimate the crustal thickness (H) and Vp/Vs ratio (k) with the H-k stacking technique. Our preliminary results show that Moho depth increases from 40 km under the northeastern Turkey to 50 km beneath northern Georgia, no station with Moho deeper than 50 km under the Lesser Caucasus. The Vp/Vs ratios in the northeastern Anatolian plateau are around 1.8, which is slightly higher than the average of global continents but consistent with the previous estimates. Further to the east, some stations show anomalously higher Vp/Vs ratio in central & southern Armenia that may be associated with Holocene volcanism. In the future, we plan to join locally measured dispersion curves to invert the velocity model without velocity-depth trade-off. We expect to resolve the velocity variations of the crust beneath this region in small scale that may be tied to the continental collision and surface volcanism. Keywords: Caucasus, receiver

  18. Lesser prairie-chicken fence collision risk across its northern distribution

    Science.gov (United States)

    Robinson, Samantha G.; Haukos, David A.; Plumb, Reid T.; Hagen, Christian A.; Pitman, James C.; Lautenbach, Joseph M.; Sullins, Daniel S.; Kraft, John D.; Lautenbach, Jonathan D.

    2016-01-01

    Livestock fences have been hypothesized to significantly contribute to mortality of lesser prairie-chickens (Tympanuchus pallidicinctus); however, quantification of mortality due to fence collisions is lacking across their current distribution. Variation in fence density, landscape composition and configuration, and land use could influence collision risk of lesser prairie-chickens. We monitored fences within 3 km of known leks during spring and fall and surveyed for signs of collision occurrence within 20 m of fences in 6 study sites in Kansas and Colorado, USA during 2013 and 2014. We assessed mortality locations of radio-tagged birds (n = 286) for evidence of fence collisions and compared distance to fence relative to random points. Additionally, we quantified locations, propensity, and frequency of fences crossed by lesser prairie-chickens. We tested for landscape and vegetative characteristics that influenced fence-cross propensity and frequency of global positioning system (GPS)-marked birds. A minimum of 12,706 fence crossings occurred by GPS-marked lesser prairie-chickens. We found 3 carcasses and 12 additional possible instances of evidence of collision during >2,800 km of surveyed fences. We found evidence for a single suspected collision based on carcass evidence for 148 mortalities of transmittered birds. Mortality locations of transmittered birds were located at distances from fences 15% farther than expected at random. Our data suggested minimal biological significance and indicated that propensity and frequency of fence crossings were random processes. Lesser prairie-chickens do not appear to be experiencing significant mortality risk due to fence collisions in Kansas and Colorado. Focusing resources on other limiting factors (i.e., habitat quality) has greater potential for impact on population demography than fence marking and removal.

  19. The predicted influence of climate change on lesser prairie-chicken reproductive parameters

    Science.gov (United States)

    Grisham, Blake A.; Boal, Clint W.; Haukos, David A.; Davis, D.; Boydston, Kathy K.; Dixon, Charles; Heck, Willard R.

    2013-01-01

    The Southern High Plains is anticipated to experience significant changes in temperature and precipitation due to climate change. These changes may influence the lesser prairie-chicken (Tympanuchus pallidicinctus) in positive or negative ways. We assessed the potential changes in clutch size, incubation start date, and nest survival for lesser prairie-chickens for the years 2050 and 2080 based on modeled predictions of climate change and reproductive data for lesser prairie-chickens from 2001-2011 on the Southern High Plains of Texas and New Mexico. We developed 9 a priori models to assess the relationship between reproductive parameters and biologically relevant weather conditions. We selected weather variable(s) with the most model support and then obtained future predicted values from climatewizard.org. We conducted 1,000 simulations using each reproductive parameter's linear equation obtained from regression calculations, and the future predicted value for each weather variable to predict future reproductive parameter values for lesser prairie-chickens. There was a high degree of model uncertainty for each reproductive value. Winter temperature had the greatest effect size for all three parameters, suggesting a negative relationship between above-average winter temperature and reproductive output. The above-average winter temperatures are correlated to La Nina events, which negatively affect lesser prairie-chickens through resulting drought conditions. By 2050 and 2080, nest survival was predicted to be below levels considered viable for population persistence; however, our assessment did not consider annual survival of adults, chick survival, or the positive benefit of habitat management and conservation, which may ultimately offset the potentially negative effect of drought on nest survival.

  20. PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling

    OpenAIRE

    Shrestha, Yashaswi; Schafer, Eric J.; Boehm, Jesse S.; Thomas, Sapana R.; He, Frank; Du, Jinyan; Wang, Shumei; Barretina, Jordi; Weir, Barbara A.; Zhao, Jean J.; Polyak, Kornelia; Golub, Todd R.; Beroukhim, Rameen; Hahn, William C.

    2011-01-01

    Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK Mitogen-Activated Protein Kinase (MAPK) pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce ...

  1. Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation

    International Nuclear Information System (INIS)

    Asur, Rajalakshmi; Balasubramaniam, Mamtha; Marples, Brian; Thomas, Robert A.; Tucker, James D.

    2010-01-01

    Many studies have examined bystander effects induced by ionizing radiation, however few have evaluated the ability of chemicals to induce similar effects. We previously reported the ability of two chemicals, mitomycin C (MMC) and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cell lines. The focus of the current study was to determine the involvement of the MAPK proteins in bystander effects induced by physical and chemical DNA damaging agents and to evaluate the effects of MAPK inhibition on bystander-induced caspase 3/7 activation. The phosphorylation levels of the MAPK proteins ERK1/2, JNK, and p38, were measured from 1 to 24 h following direct or bystander exposure to MMC, PHL or radiation. We observed transient phosphorylation, at early time points, of all 3 proteins in bystander cells. We also evaluated the effect of MAPK inhibition on bystander-induced caspase 3/7 activity to determine the role of MAPK proteins in bystander-induced apoptosis. We observed bystander-induced activation of caspase 3/7 in bystander cells. Inhibition of MAPK proteins resulted in a decrease in caspase 3/7 activity at the early time points, and the caspase activity increased (in the case of ERK inhibition) or returned to basal levels (in the case of JNK or p38 inhibition) between 12 and 24 h. PHL is considered to be a radiomimetic agent, however in the present study PHL behaved more like a chemical and not like radiation in terms of MAPK phosphorylation. These results point to the involvement of MAPK proteins in the bystander effect induced by radiation and chemicals and provide additional evidence that this response is not limited to radiation but is a generalized stress response in cells.

  2. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    International Nuclear Information System (INIS)

    Peng, Ting; Wang, Wei-Na; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-01-01

    Highlights: • Cd 2+ induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd 2+ . • DsRNA-suppression of LvCdc42 and MAPKs during Cd 2+ stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd 2+ stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd 2+ . They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses

  3. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Ting; Wang, Wei-Na, E-mail: weina63@aliyun.com; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-06-15

    Highlights: • Cd{sup 2+} induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd{sup 2+}. • DsRNA-suppression of LvCdc42 and MAPKs during Cd{sup 2+} stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd{sup 2+} stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd{sup 2+}. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses.

  4. Is Eurasian October snow cover extent increasing?

    International Nuclear Information System (INIS)

    Brown, R D; Derksen, C

    2013-01-01

    A number of recent studies present evidence of an increasing trend in Eurasian snow cover extent (SCE) in the October snow onset period based on analysis of the National Oceanic and Atmospheric Administration (NOAA) historical satellite record. These increases are inconsistent with fall season surface temperature warming trends across the region. Using four independent snow cover data sources (surface observations, two reanalyses, satellite passive microwave retrievals) we show that the increasing SCE is attributable to an internal trend in the NOAA CDR dataset to chart relatively more October snow cover extent over the dataset overlap period (1982–2005). Adjusting the series for this shift results in closer agreement with other independent datasets, stronger correlation with continentally-averaged air temperature anomalies, and a decrease in SCE over 1982–2011 consistent with surface air temperature warming trends over the same period. (letter)

  5. The extent of forest in dryland biomes

    Science.gov (United States)

    Jean-Francois Bastin; Nora Berrahmouni; Alan Grainger; Danae Maniatis; Danilo Mollicone; Rebecca Moore; Chiara Patriarca; Nicolas Picard; Ben Sparrow; Elena Maria Abraham; Kamel Aloui; Ayhan Atesoglu; Fabio Attore; Caglar Bassullu; Adia Bey; Monica Garzuglia; Luis G. GarcÌa-Montero; Nikee Groot; Greg Guerin; Lars Laestadius; Andrew J. Lowe; Bako Mamane; Giulio Marchi; Paul Patterson; Marcelo Rezende; Stefano Ricci; Ignacio Salcedo; Alfonso Sanchez-Paus Diaz; Fred Stolle; Venera Surappaeva; Rene Castro

    2017-01-01

    Dryland biomes cover two-fifths of Earth’s land surface, but their forest area is poorly known. Here, we report an estimate of global forest extent in dryland biomes, based on analyzing more than 210,000 0.5-hectare sample plots through a photo-interpretation approach using large databases of satellite imagery at (i) very high spatial resolution and (ii) very high...

  6. Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex

    Science.gov (United States)

    Xing, Lei; Larsen, Rylan S; Bjorklund, George Reed; Li, Xiaoyan; Wu, Yaohong; Philpot, Benjamin D; Snider, William D; Newbern, Jason M

    2016-01-01

    Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability. DOI: http://dx.doi.org/10.7554/eLife.11123.001 PMID:26848828

  7. p38 MAPK inhibitors: a patent review (2012 - 2013).

    Science.gov (United States)

    Bühler, Stefanie; Laufer, Stefan A

    2014-05-01

    The p38 MAPK is a ubiquitous target in the research-based pharmaceutical industry. It plays a decisive role in the regulation of the production of proinflammatory cytokines. Since novel biological therapies have revolutionized the treatment of chronic inflammatory diseases, an intensive global search is underway for small molecules for the same application. Herein, the patents and the corresponding publications of international companies, which focus on the development and identification of a new generation of small-molecule p38 inhibitors, are summarized. The most promising approach is the development of linear binders, which induce a glycine flip at Gly110 of the kinase hinge region by a carbonyl oxygen atom of the respective ligand. The major focus of the patent works was the application of molecules in new indications. Previous applications were in the treatment of rheumatoid arthritis; currently, there are several new applications, including pulmonary diseases, cancer and Alzheimer's disease. Targeting p38 upstream kinases and downstream effectors has also proved to be a very promising step in the development of more effective inhibitors. A further trend is drug combination, applied to a wide range of indications, such as chronic obstructive pulmonary disease and cancer.

  8. Research Misconduct—Definitions, Manifestations and Extent

    Directory of Open Access Journals (Sweden)

    Lutz Bornmann

    2013-10-01

    Full Text Available In recent years, the international scientific community has been rocked by a number of serious cases of research misconduct. In one of these, Woo Suk Hwang, a Korean stem cell researcher published two articles on research with ground-breaking results in Science in 2004 and 2005. Both articles were later revealed to be fakes. This paper provides an overview of what research misconduct is generally understood to be, its manifestations and the extent to which they are thought to exist.

  9. Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

    Science.gov (United States)

    Shaw, Julia G.; Friedman, Jennifer F.

    2011-01-01

    Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed. PMID:21738863

  10. Oxynoemacheilus zarzianus, a new loach from the Lesser Zab River drainage in Iraqi Kurdistan (Teleostei: Nemacheilidae).

    Science.gov (United States)

    Freyhof, Jörg; Geiger, Matthias

    2017-06-02

    Oxynoemacheilus zarzianus, new species, is described from the Lesser Zab River drainage, a tributary of the lower Tigris. It is distinguished from other Oxynoemacheilus species in the Tigris drainage by having a slightly emarginate caudal fin, no suborbital groove in males, a complete lateral line, the posterior process of the bony air-bladder capsule directed posteriorly, the flank and posterior part of back covered by scales, short barbels and a deep caudal peduncle. It is the fourth Oxynoemacheilus species known from the Lesser Zab drainage, where such loaches seem to be highly isolated in headwaters. Oxynoemacheilus species diversity in the Euphrates and Tigris drainage is exceptional high. Today 22 species are known from the entire Euphrates and Tigris drainage and 15 from the Tigris drainage alone.

  11. Intermittent Solar Ammonia Absorption Cycle (ISAAC) refrigeration for lesser developed countries

    Science.gov (United States)

    Erickson, Donald C.

    1990-02-01

    The Intermittent Solar Ammonia Absorption Cycle (ISAAC) refrigerator is a solar thermal technology which provides low cost, efficient, reliable ice-making to areas without ready access to electricity. An ISAAC refrigeration system consists of a compound parabolic solar collector, two pressure vessels, a condenser, a cold box or refrigerated space, and simple connective piping -- no moving parts or electrical components. Most parts are simple construction or plumbing grade materials, locally available in many remote areas. This technology has numerous potential benefits in lesser developed countries both by providing a cheap, reliable source of ice, and, since manufacture requires only semi-skilled labor, a source of employment to the local economy. Applications include vaccine storage for health care clinics; fish, meat, and dairy product storage; and personal consumption. Importantly, this technology increases the quality of life for people in lesser developed countries without depleting fossil fuel resources or increasing the release of greenhouse gases such as CO2 and chlorofluorocarbons.

  12. Spatial differences in growth of lesser sandeel in the North Sea

    DEFF Research Database (Denmark)

    Rindorf, Anna; Wright, Peter J.; Jensen, Henrik

    2016-01-01

    Lesser sandeel, Ammodytes marinus, is a key prey to a variety of North Sea predators, including species such as single load seabirds which are highly sensitive to prey size and condition. Whilst differences in weight at age across the North Sea have been investigated previously, the scale and cause...... of this variation as well as the potential link to spatial differences in predator performance remains unknown. This study presents an analysis of spatial patterns in length and condition of the lesser sandeel in the North Sea and the relationship of these with physical and biological factors. Both mean length...... considerably both spatially and temporally, resulting in 4 fold and 1.9 fold variations in the number of sandeels required to obtain a specific weight, respectively. Hence, the value of sandeel as prey to single load predators varies considerably with values in central and northeastern North Sea being...

  13. Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

    Directory of Open Access Journals (Sweden)

    Julia G. Shaw

    2011-01-01

    Full Text Available Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed.

  14. Sphingosine-1-Phosphate Mediates ICAM-1-Dependent Monocyte Adhesion through p38 MAPK and p42/p44 MAPK-Dependent Akt Activation

    Science.gov (United States)

    Lin, Chih-Chung; Lee, I-Ta; Hsu, Chun-Hao; Hsu, Chih-Kai; Chi, Pei-Ling; Hsiao, Li-Der; Yang, Chuen-Mao

    2015-01-01

    Up-regulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Sphingosine-1-phosphate (S1P) has been shown to play a key role in inflammation via adhesion molecules induction, and then causes lung injury. However, the mechanisms underlying S1P-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. The effect of S1P on ICAM-1 expression was determined by Western blot and real-time PCR. The involvement of signaling pathways in these responses was investigated by using the selective pharmacological inhibitors and transfection with siRNAs. S1P markedly induced ICAM-1 expression and monocyte adhesion which were attenuated by pretreatment with the inhibitor of S1PR1 (W123), S1PR3 (CAY10444), c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), PI3K (LY294002), or AP-1 (Tanshinone IIA) and transfection with siRNA of S1PR1, S1PR3, c-Src, EGFR, PDGFR, p38, p42, JNK1, c-Jun, or c-Fos. We observed that S1P-stimulated p42/p44 MAPK and p38 MAPK activation was mediated via a c-Src/EGFR and PDGFR-dependent pathway. S1P caused the c-Src/EGFR/PDGFR complex formation. On the other hand, we demonstrated that S1P induced p42/p44 MAPK and p38 MAPK-dependent Akt activation. In addition, S1P-stimulated JNK1/2 phosphorylation was attenuated by SP600125 or PP1. Finally, S1P enhanced c-Fos mRNA levels and c-Jun phosphorylation. S1P-induced c-Jun activation was reduced by PP1, AG1478, AG1296, U0126, SP600125, SB202190, or LY294002. These results demonstrated that S1P-induced ICAM-1 expression and monocyte adhesion were mediated through S1PR1/3/c-Src/EGFR, PDGFR/p38 MAPK, p42/p44 MAPK/Akt-dependent AP-1 activation. PMID:25734900

  15. First record of the Lesser Horseshoe bat, Rhinolophus hipposideros (Bechstein, 1800) (Rhinolophidae, Chiroptera) from Syria

    OpenAIRE

    Shehab, Adwan; Mamkhair, Inrahim; Amr, Zuhair

    2007-01-01

    Abstract The lesser horseshoe bat Rhinolophus hipposideros was recorded for the first time from Syria in 2005-06. Two solitary hibernating specimens (a male and a female) were collected from an underground cave in Basofan village, NW of Aleppo, and from Al Marqab Citadel, Banyas. External and cranial measurements are given for both specimens. The list of recorded species of bats of Syria includes 17 species. Riassunto&l...

  16. Impacts of a volcanic eruption on the forest birdcommunity of Montserrat, Lesser Antilles.

    Science.gov (United States)

    B. DALSGAARD; G. M. HILTON; G. A. L. GRAY; L. AYMER; J. BOATSWAIN; J. FENTON DALEY; J. MARTIN; L. MARTIN; P. MURRAIN; W. J. ARENDT; W. OLESEN GIBBONSD

    2007-01-01

    Volcanic eruptions are an important and natural source of catastrophic disturbance to ecological communities. However, opportunities to study them are relatively rare. Here we report on the effects of the eruption of the Soufrière Hills volcano on the forest bird community of the Lesser Antillean island of Montserrat. The island’s species-poor avifauna includes 11...

  17. The relative contribution of climate to changes in lesser prairie-chicken abundance

    Science.gov (United States)

    Ross, Beth E.; Haukos, David A.; Hagen, Christian A.; Pitman, James

    2016-01-01

    Managing for species using current weather patterns fails to incorporate the uncertainty associated with future climatic conditions; without incorporating potential changes in climate into conservation strategies, management and conservation efforts may fall short or waste valuable resources. Understanding the effects of climate change on species in the Great Plains of North America is especially important, as this region is projected to experience an increased magnitude of climate change. Of particular ecological and conservation interest is the lesser prairie-chicken (Tympanuchus pallidicinctus), which was listed as “threatened” under the U.S. Endangered Species Act in May 2014. We used Bayesian hierarchical models to quantify the effects of extreme climatic events (extreme values of the Palmer Drought Severity Index [PDSI]) relative to intermediate (changes in El Niño Southern Oscillation) and long-term climate variability (changes in the Pacific Decadal Oscillation) on trends in lesser prairie-chicken abundance from 1981 to 2014. Our results indicate that lesser prairie-chicken abundance on leks responded to environmental conditions of the year previous by positively responding to wet springs (high PDSI) and negatively to years with hot, dry summers (low PDSI), but had little response to variation in the El Niño Southern Oscillation and the Pacific Decadal Oscillation. Additionally, greater variation in abundance on leks was explained by variation in site relative to broad-scale climatic indices. Consequently, lesser prairie-chicken abundance on leks in Kansas is more strongly influenced by extreme drought events during summer than other climatic conditions, which may have negative consequences for the population as drought conditions intensify throughout the Great Plains.

  18. GIS habitat analysis for lesser prairie-chickens in southeastern New Mexico

    OpenAIRE

    Johnson, Kristine; Neville, Teri B; Neville, Paul

    2006-01-01

    Abstract Background We conducted Geographic Information System (GIS) habitat analyses for lesser prairie-chicken (LPCH, Tympanuchus pallidicinctus) conservation planning. The 876,799 ha study area included most of the occupied habitat for the LPCH in New Mexico. The objectives were to identify and quantify: 1. suitable LPCH habitat in New Mexico, 2. conversion of native habitats, 3. potential for habitat restoration, and 4. unsuitable habitat available for oil and gas activities. Results We f...

  19. Hepatocyte cytoskeleton during ischemia and reperfusion influence of ANP-mediated p38 MAPK activation

    Institute of Scientific and Technical Information of China (English)

    Melanie Keller; Alexander L Gerbes; Stefanie Kulhanek-Heinze; Tobias Gerwig; Uwe Grützner; Nico van Rooijen; Angelika M Vollmar; Alexandra K Kiemer

    2005-01-01

    AIM: To determine functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischemia and reperfusion.METHODS: For in vivo experiments, animals received ANP (5 μg/kg) intravenously. In a different experimental setting, isolated rat livers were perfused with KH-buffer ±ANP (200 nmol/L)±SB203580 (2 μmol/L). Liverswere then kept under ischemic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hsp27 were determined by Western blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin distribution was determined by confocal microscopy.RESULTS: We first confirmed that ANP preconditioning leads to an activation of p38 MAPK and observedalterations of the cytoskeleton in hepatocytes of ANPpreconditioned organs. ANP induced an increase of hepatic F-actin after ischemia, which could be prevented by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580.CONCLUSION: This study reveals that ANP-mediated p38 MAPK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first time shows functional consequences of ANP-induced hepatic p38 MAPK activation.

  20. The problem of lesser evil within the context of public health

    Directory of Open Access Journals (Sweden)

    Janusz Sytnik-Czetwertyński

    2016-10-01

    Szkoła Zdrowia Publicznego w Warszawie, Poland     Abstract   The issue of public health also includes broad ethical questions. It is here for instance that we find so-called decisions of conscience. Since medical practice is full of moral dilemmas, transferred into the domain of public health, for instance when a doctor decides to provide, in individual cases, costly medical procedures while being simultaneously aware that the funds used for these procedures, could save many more people whose ailments are less costly. These situations force the medical practitioner into making a decision, despite the fact that all the possible choices are morally reprehensible . There exist many moral dilemmas, where the person making the decision cannot find a satisfactory solution, while also being forced to make a decision. Normally, the decision maker then calls upon the category of so-called lesser evil. But this category is no justification – lesser evil is still evil. Which is why it is worth asking what the situation of lesser evil is for the decision maker . What is a moral choice within a public health policy?   Key words: public health, the ethical dilemma, naturalism

  1. Assessing range-wide habitat suitability for the Lesser Prairie-Chicken

    Science.gov (United States)

    Jarnevich, Catherine S.; Holcombe, Tracy R.; Grisham, Blake A.; Timmer, Jennifer M.; Boal, Clint W.; Butler, Matthew; Pitman, James C.; Kyle, Sean; Klute, David; Beauprez, Grant M.; Janus, Allan; Van Pelt, William E.

    2016-01-01

    Population declines of many wildlife species have been linked to habitat loss incurred through land-use change. Incorporation of conservation planning into development planning may mitigate these impacts. The threatened Lesser Prairie-Chicken (Tympanuchus pallidicinctus) is experiencing loss of native habitat and high levels of energy development across its multijurisdictional range. Our goal was to explore relationships of the species occurrence with landscape characteristics and anthropogenic effects influencing its distribution through evaluation of habitat suitability associated with one particular habitat usage, lekking. Lekking has been relatively well-surveyed, though not consistently, in all jurisdictions. All five states in which Lesser Prairie-Chickens occur cooperated in development of a Maxent habitat suitability model. We created two models, one with state as a factor and one without state. When state was included it was the most important predictor, followed by percent of land cover consisting of known or suspected used vegetation classes within a 5000 m area around a lek. Without state, land cover was the most important predictor of relative habitat suitability for leks. Among the anthropogenic predictors, landscape condition, a measure of human impact integrated across several factors, was most important, ranking third in importance without state. These results quantify the relative suitability of the landscape within the current occupied range of Lesser Prairie-Chickens. These models, combined with other landscape information, form the basis of a habitat assessment tool that can be used to guide siting of development projects and targeting of areas for conservation.

  2. Interactions of raptors and Lesser Prairie-Chickens at leks in the Texas Southern High Plains

    Science.gov (United States)

    Behney, Adam C.; Boal, Clint W.; Whitlaw, Heather A.; Lucia, Duane R.

    2011-01-01

    We examined behavioral interactions of raptors, Chihuahuan Ravens (Corvus cryptoleucus), and Lesser Prairie-Chickens (Tympanuchus pallidicinctus) at leks in the Texas Southern High Plains. Northern Harriers (Circus cyaneus) and Swainson's Hawks (Buteo swainsoni) were the most common raptors observed at leks. Only 15 of 61 (25%) raptor encounters at leks (0.09/hr) resulted in a capture attempt (0.02/hr). Mean (± SD) time for Lesser Prairie-Chickens to return to lekking behavior following a raptor encounter was 4.2 ± 5.5 min suggesting the disturbance had little influence on lekking behaviors. Lesser Prairie-Chickens engaged in different escape behaviors depending on raptor species and, generally, did not respond to ravens suggesting they are able to assess different predation risks. The raptors in our study area posed little predation risk to lekking prairie-chickens. Behavioral disturbance at leks appears minimal due to the lack of successful predation events, low raptor encounter rates, and short time to return to lekking behavior.

  3. Intramuscular Lipoma-Induced Occipital Neuralgia on the Lesser Occipital Nerve.

    Science.gov (United States)

    Han, Hyun Ho; Kim, Hak Soo; Rhie, Jong Won; Moon, Suk Ho

    2016-06-01

    Occipital neuralgia (ON) is commonly characterized by a neuralgiform headache accompanied by a paroxysmal burning sensation in the dermatome area of the greater, lesser, or third occipital nerve. The authors report a rare case of ON caused by an intramuscular lipoma originating from the lesser occipital nerve.A 52-year-old man presented with sharp pain in the left postauricular area with a 3 × 2-cm palpable mass. Computed tomography revealed a mass suspiciously resembling an intramuscular lipoma within splenius muscle. In the operation field, a protruding mass causing stretching of the lesser occipital nerve was found. After complete resection, the neuralgiform headache symptom had resolved and the intramuscular lipoma was confirmed through histopathology.Previous studies on the causes of ON have reported that variation in normal anatomic structures results in nerve compression. Occipital neuralgia, however, caused by intramuscular lipomas in splenius muscles have not been previously reported, and the dramatic resolution following surgery makes it an interesting case worth reporting.

  4. 78 FR 75306 - Endangered and Threatened Wildlife and Plants; Listing the Lesser Prairie-Chicken as a Threatened...

    Science.gov (United States)

    2013-12-11

    ...; 4500030113] RIN 1018-AY21 Endangered and Threatened Wildlife and Plants; Listing the Lesser Prairie-Chicken... the conservation of the lesser prairie-chicken (Tympanuchus pallidicinctus). In addition, we announce... prairie-chicken as a threatened species under the Act. We also announce the availability of the final...

  5. Long-term lesser prairie-chicken nest ecology in response to grassland management

    Science.gov (United States)

    Fritts, Sarah R.; Grisham, Blake A.; Haukos, David A.; Boal, Clint W.; Patten, Michael; Wolfe, Don H.; Dixon, Charles; Cox, Robert D.; Heck, Willard R.

    2016-01-01

    Long-term population and range declines from habitat loss and fragmentation caused the lesser prairie-chicken (Tympanuchus pallidicinctus) to be a species of concern throughout its range. Current lesser prairie-chicken range in New Mexico and Texas is partially restricted to sand shinnery oak (Quercus havardii; hereafter shinnery oak) prairies, on which cattle grazing is the main socioeconomic driver for private landowners. Cattle producers within shinnery oak prairies often focus land management on shrub eradication using the herbicide tebuthiuron to promote grass production for forage; however, herbicide application alone, and in combination with grazing, may affect nest site selection and nest survival of lesser prairie-chickens through the reduction of shinnery oak and native grasses. We used a controlled, paired, completely randomized design study to assess the influence of grazing and tebuthiuron application and their combined use on nest site selection and nest survival from 2001 to 2010 in Roosevelt County, New Mexico, USA at 2 spatial scales (i.e., treatment and microhabitat) in 4 treatments: tebuthiuron with grazing, tebuthiuron without grazing, no tebuthiuron with grazing, and a control of no tebuthiuron and no grazing. Grazing treatment was a short-duration system in which plots were grazed once during the dormant season and once during the growing season. Stocking rate was calculated each season based on measured forage production and applied to remove ≤25% of available herbaceous material per season. At the treatment scale, we compared nest site selection among treatments using 1-way χ2 tests and nest survival among treatments using a priori candidate nest survival models in Program MARK. At the microhabitat scale, we identified important habitat predictors of nest site selection and nest survival using logistic regression and a priori candidate nest survival models in Program MARK, respectively. Females typically used treatments as expected and

  6. Nonbreeding home‐range size and survival of lesser prairie‐chickens

    Science.gov (United States)

    Robinson, Samantha G.; Haukos, David A.; Plumb, Reid T.; Lautenbach, Joseph M.; Sullins, Daniel S.; Kraft, John D.; Lautenbach, Jonathan D.; Hagen, Christian A.; Pitman, James C.

    2018-01-01

    The lesser prairie‐chicken (Tympanuchus pallidicinctus), a species of conservation concern with uncertain regulatory status, has experienced population declines over the past century. Most research on lesser prairie‐chickens has focused on the breeding season, with little research conducted during the nonbreeding season, a period that exerts a strong influence on demography in other upland game birds. We trapped lesser prairie‐chickens on leks and marked them with either global positioning system (GPS) satellite or very high frequency (VHF) transmitters to estimate survival and home‐range size during the nonbreeding season. We monitored 119 marked lesser prairie‐chickens in 3 study areas in Kansas, USA, from 16 September to 14 March in 2013, 2014, and 2015. We estimated home‐range size using Brownian Bridge movement models (GPS transmitters) and fixed kernel density estimators (VHF transmitters), and female survival using Kaplan–Meier known‐fate models. Average home‐range size did not differ between sexes. Estimated home‐range size was 3 times greater for individuals fitted with GPS satellite transmitters ( = 997 ha) than those with VHF transmitters ( = 286 ha), likely a result of the temporal resolution of the different transmitters. Home‐range size of GPS‐marked birds increased 2.8 times relative to the breeding season and varied by study area and year. Home‐range size was smaller in the 2013–2014 nonbreeding season ( = 495 ha) than the following 2 nonbreeding seasons ( = 1,290 ha and  = 1,158 ha), corresponding with drought conditions of 2013, which were alleviated in following years. Female survival () was high relative to breeding season estimates, and did not differ by study area or year ( = 0.73 ± 0.04 [SE]). Future management could remain focused on the breeding season because nonbreeding survival was 39–44% greater than the previous breeding season; however, considerations of total space

  7. Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

    International Nuclear Information System (INIS)

    Yi, TacGhee; Kim, Hye-Jin; Cho, Je-Yoel; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa

    2006-01-01

    Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity

  8. Parainfluenza Virus Type 1 Induces Epithelial IL-8 Production via p38-MAPK Signalling

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Galván Morales

    2014-01-01

    Full Text Available Human parainfluenza virus type 1 (HPIV-1 is the most common cause of croup in infants. The aim of this study was to describe molecular mechanisms associated with IL-8 production during HPIV-1 infection and the role of viral replication in MAPK synthesis and activation. An in vitro model of HPIV-1 infection in the HEp-2 and A549 cell lines was used; a kinetic-based ELISA for IL-8 detection was also used, phosphorylation of the mitogen-activated protein kinases (MAPKs was identified by Western blot analysis, and specific inhibitors for each kinase were used to identify which MAPK was involved. Inactivated viruses were used to assess whether viral replication is required for IL-8 production. Results revealed a gradual increase in IL-8 production at different selected times, when phosphorylation of MAPK was detected. The secretion of IL-8 in the two cell lines infected with the HPIV-1 is related to the phosphorylation of the MAPK as well as viral replication. Inhibition of p38 suppressed the secretion of IL-8 in the HEp-2 cells. No kinase activation was observed when viruses were inactivated.

  9. Absence of ERK5/MAPK7 delays tumorigenesis in Atm−/− mice

    Science.gov (United States)

    Rovira-Clavé, Xavier; Gamez, Celina Paola Vasquez; Soriano, Francesc X.; Reina, Manuel; Espel, Enric

    2016-01-01

    Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm−/− mice. Compared with Atm−/− thymocytes, Mapk7−/−Atm−/− thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm−/− mice by partially restoring the DNA damage response in thymocytes. PMID:27793024

  10. Absence of ERK5/MAPK7 delays tumorigenesis in Atm-/- mice.

    Science.gov (United States)

    Granados-Jaén, Alba; Angulo-Ibáñez, Maria; Rovira-Clavé, Xavier; Gamez, Celina Paola Vasquez; Soriano, Francesc X; Reina, Manuel; Espel, Enric

    2016-11-15

    Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm-/- mice. Compared with Atm-/- thymocytes, Mapk7-/-Atm-/- thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm-/- mice by partially restoring the DNA damage response in thymocytes.

  11. Mitogen-activated protein kinase (MAPK) dynamics determine cell fate in the yeast mating response.

    Science.gov (United States)

    Li, Yang; Roberts, Julie; AkhavanAghdam, Zohreh; Hao, Nan

    2017-12-15

    In the yeast Saccharomyces cerevisiae , the exposure to mating pheromone activates a prototypic mitogen-activated protein kinase (MAPK) cascade and triggers a dose-dependent differentiation response. Whereas a high pheromone dose induces growth arrest and formation of a shmoo-like morphology in yeast cells, lower pheromone doses elicit elongated cell growth. Previous population-level analysis has revealed that the MAPK Fus3 plays an important role in mediating this differentiation switch. To further investigate how Fus3 controls the fate decision process at the single-cell level, we developed a specific translocation-based reporter for monitoring Fus3 activity in individual live cells. Using this reporter, we observed strikingly different dynamic patterns of Fus3 activation in single cells differentiated into distinct fates. Cells committed to growth arrest and shmoo formation exhibited sustained Fus3 activation. In contrast, most cells undergoing elongated growth showed either a delayed gradual increase or pulsatile dynamics of Fus3 activity. Furthermore, we found that chemically perturbing Fus3 dynamics with a specific inhibitor could effectively redirect the mating differentiation, confirming the causative role of Fus3 dynamics in driving cell fate decisions. MAPKs mediate proliferation and differentiation signals in mammals and are therapeutic targets in many cancers. Our results highlight the importance of MAPK dynamics in regulating single-cell responses and open up the possibility that MAPK signaling dynamics could be a pharmacological target in therapeutic interventions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Live-cell microscopy reveals small molecule inhibitor effects on MAPK pathway dynamics.

    Directory of Open Access Journals (Sweden)

    Daniel J Anderson

    Full Text Available Oncogenic mutations in the mitogen activated protein kinase (MAPK pathway are prevalent in human tumors, making this pathway a target of drug development efforts. Recently, ATP-competitive Raf inhibitors were shown to cause MAPK pathway activation via Raf kinase priming in wild-type BRaf cells and tumors, highlighting the need for a thorough understanding of signaling in the context of small molecule kinase inhibitors. Here, we present critical improvements in cell-line engineering and image analysis coupled with automated image acquisition that allow for the simultaneous identification of cellular localization of multiple MAPK pathway components (KRas, CRaf, Mek1 and Erk2. We use these assays in a systematic study of the effect of small molecule inhibitors across the MAPK cascade either as single agents or in combination. Both Raf inhibitor priming as well as the release from negative feedback induced by Mek and Erk inhibitors cause translocation of CRaf to the plasma membrane via mechanisms that are additive in pathway activation. Analysis of Erk activation and sub-cellular localization upon inhibitor treatments reveals differential inhibition and activation with the Raf inhibitors AZD628 and GDC0879 respectively. Since both single agent and combination studies of Raf and Mek inhibitors are currently in the clinic, our assays provide valuable insight into their effects on MAPK signaling in live cells.

  13. Plasticity of the MAPK signaling network in response to mechanical stress.

    Directory of Open Access Journals (Sweden)

    Andrea M Pereira

    Full Text Available Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms facilitate the crosstalk between the components of these cascades. Yet, the combinatorial complexity of potential molecular interactions between these elements have prevented the understanding of their concerted functions. To analyze the plasticity of the MAPK signaling network in response to mechanical stress we performed a non-saturating epistatic screen in resting and stretched conditions employing as readout a JNK responsive dJun-FRET biosensor. By knocking down MAPKs, and JNK pathway regulators, singly or in pairs in Drosophila S2R+ cells, we have uncovered unexpected regulatory links between JNK cascade kinases, Rho GTPases, MAPKs and the JNK phosphatase Puc. These relationships have been integrated in a system network model at equilibrium accounting for all experimentally validated interactions. This model allows predicting the global reaction of the network to its modulation in response to mechanical stress. It also highlights its context-dependent sensitivity.

  14. MKK3 Was Involved in Larval Settlement of the Barnacle Amphibalanus amphitrite through Activating the Kinase Activity of p38MAPK

    KAUST Repository

    Zhang, Gen

    2013-07-29

    The p38 mitogen-activated protein kinase (p38MAPK) plays a key role in larval settlement of the barnacle Amphibalanus amphitrite. To study the signaling pathway associated with p38MAPK during larval settlement, we sought to identify the upstream kinase of p38MAPK. Three MKKs (MKK3, MKK4 and MKK7) and three MAPKs (p38MAPK, ERK and JNK) in A. amphitrite were cloned and recombinantly expressed in E. coli. Through kinase assays, we found that MKK3, but not MKK4 or MKK7, phosphorylated p38MAPK. Furthermore, MKK3 activity was specific to p38MAPK, as it did not phosphorylate ERK or JNK. To further investigate the functional relationship between MKK3 and p38MAPK in vivo, we studied the localization of phospho-MKK3 (pMKK3) and MKK3 by immunostaining. Consistent with the patterns of p38MAPK and phospho-p38MAPK (pp38MAPK), pMKK3 and MKK3 mainly localized to the antennules of the cyprids. Western blot analysis revealed that pMKK3 levels, like pp38MAPK levels, were elevated at cyprid stage, compared to nauplii and juvenile stages. Moreover, pMKK3 levels increased after treatment with adult barnacle crude extracts, suggesting that MKK3 might mediate the stimulatory effects of adult barnacle extracts on the p38MAPK pathway. © 2013 Zhang et al.

  15. MKK3 Was Involved in Larval Settlement of the Barnacle Amphibalanus amphitrite through Activating the Kinase Activity of p38MAPK

    KAUST Repository

    Zhang, Gen; He, Li-Sheng; Wong, Yue Him; Qian, Pei-Yuan

    2013-01-01

    The p38 mitogen-activated protein kinase (p38MAPK) plays a key role in larval settlement of the barnacle Amphibalanus amphitrite. To study the signaling pathway associated with p38MAPK during larval settlement, we sought to identify the upstream kinase of p38MAPK. Three MKKs (MKK3, MKK4 and MKK7) and three MAPKs (p38MAPK, ERK and JNK) in A. amphitrite were cloned and recombinantly expressed in E. coli. Through kinase assays, we found that MKK3, but not MKK4 or MKK7, phosphorylated p38MAPK. Furthermore, MKK3 activity was specific to p38MAPK, as it did not phosphorylate ERK or JNK. To further investigate the functional relationship between MKK3 and p38MAPK in vivo, we studied the localization of phospho-MKK3 (pMKK3) and MKK3 by immunostaining. Consistent with the patterns of p38MAPK and phospho-p38MAPK (pp38MAPK), pMKK3 and MKK3 mainly localized to the antennules of the cyprids. Western blot analysis revealed that pMKK3 levels, like pp38MAPK levels, were elevated at cyprid stage, compared to nauplii and juvenile stages. Moreover, pMKK3 levels increased after treatment with adult barnacle crude extracts, suggesting that MKK3 might mediate the stimulatory effects of adult barnacle extracts on the p38MAPK pathway. © 2013 Zhang et al.

  16. Characteristics of lesser prairie-chicken (Tympanuchus pallidicinctus) long-distance movements across their distribution

    Science.gov (United States)

    Earl, Julia E.; Fuhlendorf, Samuel D.; Haukos, David A.; Tanner, Ashley M.; Elmore, Dwayne; Carleton, Scott A.

    2016-01-01

    Long-distance movements are important adaptive behaviors that contribute to population, community, and ecosystem connectivity. However, researchers have a poor understanding of the characteristics of long-distance movements for most species. Here, we examined long-distance movements for the lesser prairie-chicken (Tympanuchus pallidicinctus), a species of conservation concern. We addressed the following questions: (1) At what distances could populations be connected? (2) What are the characteristics and probability of dispersal movements? (3) Do lesser prairie-chickens display exploratory and round-trip movements? (4) Do the characteristics of long-distance movements vary by site? Movements were examined from populations using satellite GPS transmitters across the entire distribution of the species in New Mexico, Oklahoma, Kansas, and Colorado. Dispersal movements were recorded up to 71 km net displacement, much farther than hitherto recorded. These distances suggest that there may be greater potential connectivity among populations than previously thought. Dispersal movements were displayed primarily by females and had a northerly directional bias. Dispersal probabilities ranged from 0.08 to 0.43 movements per year for both sexes combined, although these movements averaged only 16 km net displacement. Lesser prairie-chickens displayed both exploratory foray loops and round-trip movements. Half of round-trip movements appeared seasonal, suggesting a partial migration in some populations. None of the long-distance movements varied by study site. Data presented here will be important in parameterizing models assessing population viability and informing conservation planning, although further work is needed to identify landscape features that may reduce connectivity among populations.

  17. Evaluation of capture techniques on lesser prairie-chicken trap injury and survival

    Science.gov (United States)

    Grisham, Blake A.; Boal, Clint W.; Mitchell, Natasia R.; Gicklhorn, Trevor S.; Borsdorf, Philip K.; Haukos, David A.; Dixon, Charles

    2015-01-01

    Ethical treatment of research animals is required under the Animal Welfare Act. This includes trapping methodologies that reduce unnecessary pain and duress. Traps used in research should optimize animal welfare conditions within the context of the proposed research study. Several trapping techniques are used in the study of lesser prairie-chickens, despite lack of knowledge of trap injury caused by the various methods. From 2006 to 2012, we captured 217, 40, and 144 lesser prairie-chickens Tympanuchus pallidicinctus using walk-in funnel traps, rocket nets, and drop nets, respectively, in New Mexico and Texas, to assess the effects of capture technique on injury and survival of the species. We monitored radiotagged, injured lesser prairie-chickens 7–65 d postcapture to assess survival rates of injured individuals. Injuries occurred disproportionately among trap type, injury type, and sex. The predominant injuries were superficial cuts to the extremities of males captured in walk-in funnel traps. However, we observed no mortalities due to trapping, postcapture survival rates of injured birds did not vary across trap types, and the daily survival probability of an injured and uninjured bird was ≥99%. Frequency and intensity of injuries in walk-in funnel traps are due to the passive nature of these traps (researcher cannot select specific individuals for capture) and incidental capture of individuals not needed for research. Comparatively, rocket nets and drop nets allow observers to target birds for capture and require immediate removal of captured individuals from the trap. Based on our results, trap injuries would be reduced if researchers monitor and immediately remove birds from walk-in funnels before they injure themselves; move traps to target specific birds and reduce recaptures; limit the number of consecutive trapping days on a lek; and use proper netting techniques that incorporate quick, efficient, trained handling procedures.

  18. Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.

    Directory of Open Access Journals (Sweden)

    Remco Visser

    Full Text Available Sotos syndrome (SoS is characterized by tall stature, characteristic craniofacial features and mental retardation. It is caused by haploinsufficiency of the NSD1 gene. In this study, our objective was to identify downstream effectors of NSD1 and to map these effectors in signaling pathways associated with growth. Genome-wide expression studies were performed on dermal fibroblasts from SoS patients with a confirmed NSD1 abnormality. To substantiate those results, phosphorylation, siRNA and transfection experiments were performed. A significant association was demonstrated with the Mitogen-Activated Protein Kinase (MAPK pathway. Members of the fibroblast growth factor family such as FGF4 and FGF13 contributed strongly to the differential expression in this pathway. In addition, a diminished activity state of the MAPK/ERK pathway was demonstrated in SoS. The Ras Interacting Protein 1 (RASIP1 was identified to exhibit upregulated expression in SoS. It was shown that RASIP1 dose-dependently potentiated bFGF induced expression of the MAPK responsive SBE reporter providing further support for a link between NSD1 and the MAPK/ERK signaling pathway. Additionally, we demonstrated NSD1 expression in the terminally differentiated hypertrophic chondrocytes of normal human epiphyseal growth plates. In short stature syndromes such as hypochondroplasia and Noonan syndrome, the activation level of the FGF-MAPK/ERK-pathway in epiphyseal growth plates is a determining factor for statural growth. In analogy, we propose that deregulation of the MAPK/ERK pathway in SoS results in altered hypertrophic differentiation of NSD1 expressing chondrocytes and may be a determining factor in statural overgrowth and accelerated skeletal maturation in SoS.

  19. p38 MAPK and MMP-9 cooperatively regulate mucus overproduction in mice exposed to acrolein fog.

    Science.gov (United States)

    Liu, Dai-Shun; Wang, Tao; Han, Su-Xia; Dong, Jia-Jia; Liao, Zeng-Lin; He, Guang-Ming; Chen, Lei; Chen, Ya-Juan; Xu, Dan; Hou, Yan; Li, Yan-Ping; Wen, Fu-Qiang

    2009-09-01

    To evaluate the role of p38 mitogen-activated protein kinase (MAPK) on mice airway inflammation, mucus production and the possible cross-talk between p38 MAPK and matrix metalloproteinase-9 (MMP-9) in mucin protein synthesis. Mice were exposed to 4.0 ppm of acrolein for 21 days with daily intraperitoneal injection of SB203580, a specific inhibitor of p38 MAPK. In control mice, sterile saline was administered instead. On days 7 and 21, mice were sacrificed to examine airway inflammation and mucus production by BALF cell counts, cytokine ELISA, and H&E and AB-PAS staining. The mRNA and protein levels of Muc5ac, p38 MAPK and MMP-9 in the lung were determined by RT-PCR, immunohistochemistry and Western blotting analysis. MMP-9 activity was measured by gelatin zymography. Both the numbers of inflammatory cells and mucus-secreting goblet cells were significantly increased in the airways of mice exposed to acrolein as compared to the control mice. Acrolein-increased phosphorylation of p38 MAPK was significantly reduced by SB203580. The airway inflammation and goblet cell hyperplasia after acrolein challenge were also attenuated by SB203580 administration. Moreover, SB203580 treatment decreased the acrolein-induced increase of Muc5ac and MMP-9 expression and MMP-9 activity in airway epithelium. The results indicate an important role of p38 MAPK in acrolein-induced airway inflammation and mucus hypersecretion in mice. The cooperation of p38 and MMP-9 may contribute to the mucin overproduction after inflammatory challenge.

  20. Canine distemper virus infection in a lesser grison (Galictis cuja: first report and virus phylogeny

    Directory of Open Access Journals (Sweden)

    Jane Megid

    2013-02-01

    Full Text Available Infectious diseases in wild animals have been increasing as a result of their habitat alterations and closer contact with domestic animals. Canine distemper virus (CDV has been reported in several species of wild carnivores, presenting a threat to wildlife conservation. We described the first case of canine distemper virus infection in lesser grison (Galictis cuja. A free-ranging individual, with no visible clinical sigs, presented sudden death after one day in captivity. Molecular diagnosis for CDV infection was performed using whole blood collected by postmortem intracardiac puncture, which resulted positive. The virus phylogeny indicated that domestic dogs were the probable source of infection.

  1. Hepatic microsomal metabolism of BDE-47 and BDE-99 by lesser snow geese and Japanese quail.

    Science.gov (United States)

    Krieger, Lisa K; Szeitz, András; Bandiera, Stelvio M

    2017-09-01

    In the present study, we investigated the oxidative biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) by liver microsomes from wild lesser snow geese (Chen caerulescens caerulescens) and domesticated Japanese quail (Coturnix japonica). Formation of hydroxy-metabolites was analyzed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method. Incubation of BDE-47 with avian liver microsomes produced sixteen hydroxy-metabolites, eight of which were identified using authentic standards. The major metabolites formed by liver microsomes from individual lesser snow geese were 4-hydroxy-2,2',3,4'-tetrabromodiphenyl ether (4-OH-BDE-42), 3-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (3-OH-BDE-47), and 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether (4'-OH-BDE-49). By comparison, 4-OH-BDE-42 and 4'-OH-BDE-49, but not 3-OH-BDE-47, were major metabolites of Japanese quail liver microsomes. Unidentified metabolites included monohydroxy- and dihydroxy-tetrabromodiphenyl ethers. Incubation of BDE-99 with avian liver microsomes produced seventeen hydroxy-metabolites, twelve of which were identified using authentic standards. The major metabolites formed by lesser snow goose liver microsomes were 2,4,5-tribromophenol, 3-OH-BDE-47, 4'-OH-BDE-49, 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether (4-OH-BDE-90), and 5'-hydroxy-2,2',4,4',5-pentabromodiphenyl ether (5'-OH-BDE-99). By comparison, the major metabolites produced by liver microsomes from Japanese quail included 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) and 2-hydroxy-2',3,4,4',5-pentabromodiphenyl ether (2-OH-BDE-123), but not 3-OH-BDE-47. Unidentified metabolites consisted of monohydroxy-pentabromodiphenyl ethers, monohydroxy-tetrabromodiphenyl ethers and dihydroxy-tetrabromodiphenyl ethers. Another difference between the two species was that formation rates of BDE-47 and BDE-99 metabolites were greater with liver

  2. Spatially explicit modeling of lesser prairie-chicken lek density in Texas

    Science.gov (United States)

    Timmer, Jennifer M.; Butler, M.J.; Ballard, Warren; Boal, Clint W.; Whitlaw, Heather A.

    2014-01-01

    As with many other grassland birds, lesser prairie-chickens (Tympanuchus pallidicinctus) have experienced population declines in the Southern Great Plains. Currently they are proposed for federal protection under the Endangered Species Act. In addition to a history of land-uses that have resulted in habitat loss, lesser prairie-chickens now face a new potential disturbance from energy development. We estimated lek density in the occupied lesser prairie-chicken range of Texas, USA, and modeled anthropogenic and vegetative landscape features associated with lek density. We used an aerial line-transect survey method to count lesser prairie-chicken leks in spring 2010 and 2011 and surveyed 208 randomly selected 51.84-km(2) blocks. We divided each survey block into 12.96-km(2) quadrats and summarized landscape variables within each quadrat. We then used hierarchical distance-sampling models to examine the relationship between lek density and anthropogenic and vegetative landscape features and predict how lek density may change in response to changes on the landscape, such as an increase in energy development. Our best models indicated lek density was related to percent grassland, region (i.e., the northeast or southwest region of the Texas Panhandle), total percentage of grassland and shrubland, paved road density, and active oil and gas well density. Predicted lek density peaked at 0.39leks/12.96km(2) (SE=0.09) and 2.05leks/12.96km(2) (SE=0.56) in the northeast and southwest region of the Texas Panhandle, respectively, which corresponds to approximately 88% and 44% grassland in the northeast and southwest region. Lek density increased with an increase in total percentage of grassland and shrubland and was greatest in areas with lower densities of paved roads and lower densities of active oil and gas wells. We used the 2 most competitive models to predict lek abundance and estimated 236 leks (CV=0.138, 95% CI=177-306leks) for our sampling area. Our results suggest that

  3. Unique structure and optics of the lesser eyes of the box jellyfish Tripedalia cystophora

    DEFF Research Database (Denmark)

    Garm, A; Andersson, F; Nilsson, Dan-E

    2008-01-01

    mere light meters. The slit eyes, comprising four cell types, are complex and highly asymmetric. They also hold a lens-like structure, but its optical power is minute. Optical modeling suggests spatial resolution, but only in one plane. These unique and intriguing traits support strong peripheral......The visual system of box jellyfish comprises a total of 24 eyes. These are of four types and each probably has a special function. To investigate this hypothesis the morphology and optics of the lesser eyes, the pit and slit eyes, were examined. The pit eyes hold one cell type only and are probably...

  4. Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment.

    Science.gov (United States)

    Filomeni, Giuseppe; Cardaci, Simone; Da Costa Ferreira, Ana Maria; Rotilio, Giuseppe; Ciriolo, Maria Rosa

    2011-08-01

    We have demonstrated previously that the complex bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N']copper(II), named [Cu(isaepy)(2)], induces AMPK (AMP-activated protein kinase)-dependent/p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38(MAPK) (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK resulted in a decrease in apoptosis and a significant reduction in phospho-active p38(MAPK) and p53. Similarly, reverse genetics of p38(MAPK) yielded a reduction in p53 and a decrease in the extent of apoptosis, confirming an exclusive hierarchy of activation that proceeds via AMPK/p38(MAPK)/p53. Fuel supplies counteracted [Cu(isaepy)(2)]-induced apoptosis and AMPK/p38(MAPK)/p53 activation, with glucose being the most effective, suggesting a role for energetic imbalance in [Cu(isaepy)(2)] toxicity. Co-administration of 3BrPA (3-bromopyruvate), a well-known inhibitor of glycolysis, and succinate dehydrogenase, enhanced apoptosis and AMPK/p38(MAPK)/p53 signalling pathway activation. Under these conditions, no toxic effect was observed in SOD (superoxide dismutase)-overexpressing SH-SY5Y cells or in PCNs (primary cortical neurons), which are, conversely, sensitized to the combined treatment with [Cu(isaepy)(2)] and 3BrPA only if grown in low-glucose medium or incubated with the glucose-6-phosphate dehydrogenase inhibitor dehydroepiandrosterone. Overall, the results suggest that NADPH deriving from the pentose phosphate pathway contributes to PCN resistance to [Cu(isaepy)(2)] toxicity and propose its employment in combination with 3BrPA as possible tool for cancer treatment. © The Authors Journal compilation © 2011 Biochemical Society

  5. [Effect of P38MAPK signal transduction pathway on apoptosis of THP-1 induced by allicin].

    Science.gov (United States)

    Liao, Yang; Chen, Jianbin; Tang, Weixue; Ge, Qunfang; Lu, Qianwei; Yang, Zesong

    2009-06-01

    The objective of this paper was to study the change of P38MAPK and Fas in the apoptosis of THP-1 cells induced by allicin. The proliferation inhibition rates of THP-1 cells after various treatments were examined by MTT assay. Apoptosis rate was determined with Annexin V- FITC/PI double staining by flow cytometry. The expression and distribution change of the phosphorylation p38MAPK (P-p38MAPK) were detected by immunohistochemical staining. The changes of P-p38 MAPK and Fas proteins were detected by Western blot. The proliferations of leukemia cell line THP-1 are inhibited by allicin. MTT assay showed that allicin can inhibit the proliferation of the THP-1 cell, and the inhibition was dependent on both dose and time. The IC50 of 72 hours was 12.8 mg x L(-1). Apoptosis rate detected by Annexin V-FITC/PI was proportional to the concentration of the allicin. After the immunohistochemical staining test, the P-p38MAPK was located in the cell nucleus and plasma, showing deep brown, when adding allicin to THP-1 cell. Western blot test showed that the P-p38MAPK proteins expression was proportional to the concentration of Allicin and was also dose dependent. The levels of P-p38MAPK in negative control group, 1/2 IC50 of 72 hours group and IC50 of 72 hours group were 0.259 8 +/- 0.013 2, 0.61 2 +/- 0.008 3 and 0.505 6 +/- 0.005 5 respectively, and the levels of Fas proteins were 0.287 4 +/- 0.008 9, 0.426 8 +/- 0.007 9 and 0.597 1 +/- 0.010 9 respectively. The difference was statistically significant when compared with the negative control group (P THP-1 cells apoptosis, and its mechanism may be related to the activation of P38MAPK/Fas.

  6. The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis.

    LENUS (Irish Health Repository)

    Matlawska-Wasowska, Ksenia

    2010-12-01

    Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.

  7. Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Hsin-Cheng Hsu

    2013-01-01

    Full Text Available Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA, which causes intracellular mitogen-activated protein kinase (MAPK signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR and rhynchophylline (RP have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p. to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg, RP (0.25 mg/kg, and valproic acid (VA, 250 mg/kg for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL-1β, IL-6, and tumor necrosis factor-α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

  8. Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats.

    Science.gov (United States)

    Hsu, Hsin-Cheng; Tang, Nou-Ying; Liu, Chung-Hsiang; Hsieh, Ching-Liang

    2013-01-01

    Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA), which causes intracellular mitogen-activated protein kinase (MAPK) signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR) and rhynchophylline (RP) have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p.) to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg), RP (0.25 mg/kg), and valproic acid (VA, 250 mg/kg) for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp) of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL)-1 β , IL-6, and tumor necrosis factor- α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

  9. Recent Advances in the Inhibition of p38 MAPK as a Potential Strategy for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Lee, Jong Kil; Kim, Nam-Jung

    2017-08-02

    P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic inflammatory diseases. Alzheimer's disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on the underlying biology of AD in cellular and animal models have indicated that p38 MAPK is capable of orchestrating diverse events related to AD, such as tau phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus, the inhibition of p38 MAPK is considered a promising strategy for the treatment of AD. In this review, we summarize recent advances in the targeting of p38 MAPK as a potential strategy for the treatment of AD and envision possibilities of p38 MAPK inhibitors as a fundamental therapeutics for AD.

  10. Application of Persistent Scatterer Interferometry (PSI) in monitoring slope movements in Nainital, Uttarakhand Lesser Himalaya, India

    Science.gov (United States)

    Yhokha, Akano; Goswami, Pradeep K.; Chang, Chung-Pai; Yen, Jiun-Yee; Ching, Kuo-En; Aruche, K. Manini

    2018-02-01

    Orogenic movements and sub-tropical climate have rendered the slopes of the Himalayan region intensely deformed and weathered. As a result, the incidences of slope failure are quite common all along the Himalayan region. The Lesser Himalayan terrane is particularly vulnerable to mass-movements owing to geological fragility, and many parts of it are bearing a high-risk of associated disaster owing to the high population density. An important step towards mitigation of such disasters is the monitoring of slope movement. Towards this, the Persistent Scatterer Interferometry (PSI) technique can be applied. In the present study, the PSI technique is employed in Lesser Himalayan town of Nainital in Uttarakhand state of India to decipher and monitor slope movements. A total of 15 multi-date ENVISAT ASAR satellite images, acquired during August 2008 to August 2010 period, were subjected to PSI, which revealed a continuous creep movement along the hillslopes located towards the eastern side of the Nainital lake. The higher reaches of the hill seem to be experiencing accelerated creep of {˜ }21 mm/year, which decreases downslope to {˜ }5 mm/year. Based on spatial pattern of varying PSI Mean LOS Velocity (MLV) values, high (H), moderate (M), low (L) and very low (S) creeping zones have been delineated in the hillslopes. Given the long history of mass movements and continuously increasing anthropogenic activities in Nainital, these results call for immediate measures to avert any future disaster in the town.

  11. A Midterm Review of Lesser Toe Arthrodesis With an Intramedullary Implant.

    Science.gov (United States)

    Harmer, James Lee; Wilkinson, Anthony; Maher, Anthony John

    2017-10-01

    Lesser toe deformities are one of the most common conditions encountered by podiatric surgeons. When conservative treatments fail surgical correction is indicated. Many surgical options have been described to address the complex nature of these deformities but no perfect solution has been reported to date. However, with the continued advancement of internal fixation technology, interphalangeal joint (IPJ) arthrodesis with an intramedullary implant may be a good option. This retrospective study presents patient reported outcomes and complications at 6 months and 3 years following lesser toe proximal interphalangeal joint (PIPJ) arthrodesis with a polyketone intrameduallary implant (Toe Grip, Orthosolutions, UK). Between September 2011 and November 2012, a total of 38 patients attended for second toe PIPJ arthrodesis by means of the Toe Grip device. At 6 months postoperation, 94.7% of patients and at 3 years postoperation, 92.8% of patients felt that their original complaint was better or much better. Health-related quality of life scores continued to improve overtime as measured by the Manchester Oxford Foot Questionnaire. Complications were generally observational and asymptomatic. The most common complications were floating toes (17.8%), mallet deformities (14.2%), metatarsalgia (17.8%), and transverse plane deformity of the toe (10.7%). This study demonstrates excellent patient-eported outcomes with minimal symptomatic complications making the "Toe Grip" implant a safe and effective alternative fixation device for IPJ arthrodesis when dealing with painful digital deformities. Therapeutic, Level IV: Case series.

  12. Social Impact Assessment: The lesser sibling in the South African EIA process?

    International Nuclear Information System (INIS)

    Hildebrandt, L.; Sandham, L.A.

    2014-01-01

    Social Impact Assessment has developed as an integral but neglected component of EIA in South Africa since it became mandatory in 1997, and has therefore been referred to as the “orphan” or “lesser sibling” of EIA, as has SIA in the UK and the US. The aim of this paper is to test this claim by reviewing the quality of a sample of SIA reports, and also to establish whether there has been any improvement in quality following the introduction of revised EIA regulations in 2006. The results confirm that SIA can be called “the lesser sibling” due to the weak grades achieved in the quality review, but also reveal that there has been a slight and consistent improvement in quality, most likely driven by best practice considerations in the absence of prescriptive regulations for SIA. Suggestions and recommendations for addressing observed weakness in SIA performance are advanced. - Highlights: • The quality of a sample of SIA reports was evaluated using a review package. • SIA reports received mostly weak grades. • Limited improvement observed from first to second regulatory regime. • Improvements most likely due to best practice considerations

  13. Temperature effects on egg development and larval condition in the lesser sandeel, Ammodytes marinus

    Science.gov (United States)

    Régnier, Thomas; Gibb, Fiona M.; Wright, Peter J.

    2018-04-01

    Understanding the influence of temperature on egg development and larval condition in planktonic fish is a prerequisite to understanding the phenological impacts of climate change on marine food-webs. The lesser sandeel, Ammodytes marinus (Raitt 1934), is a key trophic link between zooplankton and many piscivorous fish, sea birds and mammals in the northeast Atlantic. Temperature-egg development relationships were determined for batches of lesser sandeel eggs. Hatching began as early as 19 days post fertilisation at 11 °C and as late as 36 days post fertilisation at 6 °C, which is faster than egg development rates reported for closely related species at the lower end of the tested temperature range. The average size of newly hatched larvae decreased with increasing incubation temperatures in early hatching larvae, but this effect was lost by the middle of the hatching period. While the study revealed important temperature effects on egg development rate, predicted variability based on the range of temperatures eggs experience in the field, suggests it is only a minor contributor to the observed inter-annual variation in hatch date.

  14. Regional Variation in mtDNA of the Lesser Prairie-Chicken

    Science.gov (United States)

    Hagen, Christian A.; Pitman, James C.; Sandercock, Brett K.; Wolfe, Don H.; Robel, Robel J.; Applegate, Roger D.; Oyler-McCance, Sara J.

    2010-01-01

    Cumulative loss of habitat and long-term decline in the populations of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) have led to concerns for the species' viability throughout its range in the southern Great Plains. For more efficient conservation past and present distributions of genetic variation need to be understood. We examined the distribution of mitochondrial DNA (mtDNA) variation in the Lesser Prairie-Chicken across Kansas, Colorado, Oklahoma, and New Mexico. Throughout the range we found little genetic differentiation except for the population in New Mexico, which was significantly different from most other publications. We did, however, find significant isolation by distance at the rangewide scale (r=0.698). We found no relationship between haplotype phylogeny and geography, and our analyses provide evidence for a post-glacial population expansion within the species that is consistent with the idea that speciation within Tympanuchus is recent. Conservation actions that increase the likelihood of genetically viable populations in the future should be evaluated for implementation.

  15. Deformation mechanisms in the frontal Lesser Himalayan Duplex in Sikkim Himalaya, India

    Science.gov (United States)

    Matin, Abdul; Mazumdar, Sweety

    2009-08-01

    Understanding deformation mechanisms in Himalayan rocks is a challenging proposition due to the complex nature of the deformed rocks and their genesis. Crustal deformation in the Himalayan thrust belt typically occurs in elastico-frictional (EF) or quasi-plastic (QP) regimes at depths controlled mainly by regional strain-rate and geothermal gradient. However, material property, grain-size and their progressive changes during deformation are also important controlling factors. We present evidence of EF deformation from Gondwana rocks developed during the emplacement of one of the frontal horses (Jorthang horse) in the Lesser Himalayan Duplex (LHD) structure associated with Lesser Himalayan rocks in the footwall of the Ramgarh thrust in the Rangit window near Jorthang in the Sikkim Himalaya. The rocks in the horse exhibit systematic changes in microand meso-structures from an undeformed protolith to cataclasite suggesting that it was emplaced under elastico-frictional conditions. Meso- to micro-scale shear fractures are seen developed in Gondwana sandstone and slate while intercalated fine-grained shale-coal-carbonates are deformed by cataclastic flow suggesting that material property and grain-size have played an important role in the deformation of the Jorthang horse. In contrast, the hanging wall schists and quartzites of the Ramgarh thrust exhibit quasi-plastic deformation structures. This suggests that the Jorthang horse was emplaced under shallower crustal conditions than the antiformally folded Ramgarh thrust sheet even though the Ramgarh sheet presently overlies the Jorthang horse.

  16. Testing competing hypotheses for chronology and intensity of lesser scaup molt during winter and spring migration

    Science.gov (United States)

    Anteau, M.J.; Anteau, A.C.E.; Afton, A.D.

    2011-01-01

    We examined chronology and intensity of molt and their relationships to nutrient reserves (lipid and protein) of Lesser Scaup (Aythya affinis) to test predictions of two competing hypotheses. The "staggered cost" hypothesis states that contour-feather molt is nutritionally costly and should not occur during nutritionally costly periods of the annual cycle unless adequate nutrients are available. The "breeding plumage" hypothesis states that prealternate molt must be complete prior to nesting, regardless of nutrient availability. Males and females were completing prebasic molt during winter (Louisiana) and had similar molt intensities. Females underwent prealternate molt during spring migration (Illinois and Minnesota) and prebreeding (Manitoba) periods; 53% and 93% of females were in moderate to heavy molt in Minnesota and Manitoba, respectively, despite experiencing other substantial nutritional costs. Intensity of prealternate molt was not correlated with lipid reserves even though females, on average, were nutritionally stressed. Molt intensity was not negatively correlated with protein reserves at any location. Chronology and intensity of prealternate molt varied little and were not temporally staggered from other nutritionally costly events. Prealternate molt did not influence nutrient reserves, and nutrient reserves likely were not the ultimate factor influencing chronology or intensity of prealternate molt of females. We surmise that nutrients required for prealternate molt come from exogenous sources and that the "staggered cost" hypothesis does not explain chronology of prealternate molt in female Lesser Scaup; rather, it appears that molt must be complete prior to nesting, consistent with the "breeding plumage" hypothesis. ?? The Cooper Ornithological Society 2011.

  17. A comment on “temporal variation in survival and recovery rates of lesser scaup”

    Science.gov (United States)

    Lindberg, Mark S.; Boomer, G. Scott; Schmutz, Joel A.; Walker, Johann A.

    2017-01-01

    Concerns about declines in the abundance of lesser scaup (Aythya affinis) have promoted a number of analyses to understand reasons for this decline. Unfortunately, most of these analyses, including that of Arnold et al. (2016 Journal of Wildlife Management 80: 850–861), are based on observational studies leading to weak inference. Although we commend the efforts of Arnold et al. (2016 Journal of Wildlife Management 80: 850–861), we think their conclusions are over-stated given their retrospective analysis. Further, we note a number of inconsistencies in their reasoning and offer alternative conclusions that can be drawn from their analysis. Given the uncertainty still surrounding management of lesser scaup, we do not believe it is prudent to abandon or greatly modify adaptive management approaches designed specifically to make optimal decisions in the face of uncertainty. The current learning-based and recursive approach to management appears to be providing adequate guidance for harvest without punctuated changes to harvest levels, as Arnold et al. (2016 Journal of Wildlife Management 80: 850–861) recommend.

  18. K-Ar geochronology and palaeomagnetism of volcanic rocks in the lesser Antilles island arc

    International Nuclear Information System (INIS)

    Briden, J.C.; Rex, D.C.; Faller, A.M.; Tomblin, J.F.

    1979-01-01

    K-Ar age determinations on rocks and minerals from 95 locations in the Lesser Antilles. An age range of 38 - 10 million years was found for the outer arc (Limestone Caribbees) but less than 7.7 million years in the inner arc (Volcanic Caribbees). From Martinique southwards the two arcs are superimposed. These age ranges fit between discontinuities in sea floor spreading in the North Atlantic at about 38 and 9 million years and a causal connection between spreading change and relocation of arc volcanicity is suggested. Paleomagnetic directions at 108 localities in 10 islands fall into normal and reversed groups with 6 sites intermediate and 5 indeterminate. The mean dipole axis is within 2% of the present rotation axis. The data generally agrees with the established geomagnetic polarity time scale but there is some suggestion of a normal polarity event at about 1.18 million years. The paleomagnetic data suggest that in the past 10 million years the Lesser Antilles have not changed their latitude or geographical orientation and the geomagnetic field has averaged that of a central axial dipole. (author)

  19. Social Impact Assessment: The lesser sibling in the South African EIA process?

    Energy Technology Data Exchange (ETDEWEB)

    Hildebrandt, L., E-mail: Leandri.hildebrandt@nwu.ac.za [African Centre for Disaster Studies, Research Focus Area: Social Transformation, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Sandham, L.A., E-mail: luke.sandham@nwu.ac.za [Environmental Assessment Research Group, School of Geo and Spatial Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa)

    2014-09-15

    Social Impact Assessment has developed as an integral but neglected component of EIA in South Africa since it became mandatory in 1997, and has therefore been referred to as the “orphan” or “lesser sibling” of EIA, as has SIA in the UK and the US. The aim of this paper is to test this claim by reviewing the quality of a sample of SIA reports, and also to establish whether there has been any improvement in quality following the introduction of revised EIA regulations in 2006. The results confirm that SIA can be called “the lesser sibling” due to the weak grades achieved in the quality review, but also reveal that there has been a slight and consistent improvement in quality, most likely driven by best practice considerations in the absence of prescriptive regulations for SIA. Suggestions and recommendations for addressing observed weakness in SIA performance are advanced. - Highlights: • The quality of a sample of SIA reports was evaluated using a review package. • SIA reports received mostly weak grades. • Limited improvement observed from first to second regulatory regime. • Improvements most likely due to best practice considerations.

  20. Testing competing hypotheses for chronology and intensity of lesser scaup molt during winter and spring migration

    Science.gov (United States)

    Anteau, Michael J.; Anteau, Andrea C.E.; Afton, Alan D.

    2011-01-01

    We examined chronology and intensity of molt and their relationships to nutrient reserves (lipid and protein) of Lesser Scaup (Aythya affinisK/i>) to test predictions of two competing hypotheses. The "staggered cost" hypothesis states that contour-feather molt is nutritionally costly and should not occur during nutritionally costly periods of the annual cycle unless adequate nutrients are available. The "breeding plumage" hypothesis states that prealternate molt must be complete prior to nesting, regardless of nutrient availability. Males and females were completing prebasic molt during winter (Louisiana) and had similar molt intensities. Females underwent prealternate molt during spring migration (Illinois and Minnesota) and prebreeding (Manitoba) periods; 53% and 93% of females were in moderate to heavy molt in Minnesota and Manitoba, respectively, despite experiencing other substantial nutritional costs. Intensity of prealternate molt was not correlated with lipid reserves even though females, on average, were nutritionally stressed. Molt intensity was not negatively correlated with protein reserves at any location. Chronology and intensity of prealternate molt varied little and were not temporally staggered from other nutritionally costly events. Prealternate molt did not influence nutrient reserves, and nutrient reserves likely were not the ultimate factor influencing chronology or intensity of prealternate molt of females. We surmise that nutrients required for prealternate molt come from exogenous sources and that the "staggered cost" hypothesis does not explain chronology of prealternate molt in female Lesser Scaup; rather, it appears that molt must be complete prior to nesting, consistent with the "breeding plumage" hypothesis.

  1. Amino acid neurotoxins in feathers of the Lesser Flamingo, Phoeniconaias minor.

    Science.gov (United States)

    Metcalf, J S; Banack, S A; Kotut, K; Krienitz, L; Codd, G A

    2013-01-01

    The Lesser Flamingo (Phoeniconaias minor) is known to use cyanobacteria (primarily Arthrospira) as a major food source in the East African Rift Valley lakes. Periodically, mass mortalities have occurred, associated with the cyanobacterial toxins (cyanotoxins), microcystins and anatoxin-a. Deposition of these cyanotoxins into P. minor feathers has been shown to occur, consistent with the presence of cyanotoxins in the livers, stomach and faecal contents after dietary intake. As cyanobacteria have been shown to also produce the neurotoxins β-N-methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB), stored wing feathers, previously recovered from flamingos which had been exposed to microcystins and anatoxin-a and had subsequently died, were analysed for these neurotoxic amino acids. Trace amounts of BMAA were detected in extracts from Lake Nakuru flamingo feathers, with DAB also present at concentrations between 3.5 and 8.5 μg g(-1) dry weight in feathers from both lakes. Toxin recovery by solid-phase extraction of feather digests was tested with spiked deuterated BMAA and showed good recovery when analysed by LC-MS/MS (80-94%). This is the first report of these neurotoxic amino acids in birds. We discuss the origin and significance of DAB, alongside other cyanotoxins of dietary origin, in the feathers of the Lesser Flamingo. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Sero-epidemiological survey on bovine tick-borne diseases in the Lesser Antilles

    International Nuclear Information System (INIS)

    Camus, E.; Maran, M.; Montenegro-James, S.; Accipe, A.

    1998-01-01

    As part of a tick-borne disease control programme in the Lesser Antilles, studies were undertaken to determine the prevalence of cowdriosis, babesiosis and anaplasmosis in an effort to determine what the impact of tick eradication would be. The epidemiological situation for bovine babesiosis and anaplasmosis is unstable in all the islands of the Lesser Antilles, but the clinical cases are only recorded in imported breeds, which represent less than 5% of the cattle population. The native cattle population react as if naturally resistant. When the A. variegatum tick eradication campaign begins, it will be necessary, by the end of the acaricide treatment regime, to immunize all the imported cattle born during that period, and possibly all of the seronegative imported cattle already on the islands. Both Antigua and Guadeloupe have a long history of infestation with the tick and both have experienced clinical cases of cowdriosis. On the other islands, less than 6% of the sera were positive and this correlates well also with an apparent absence of clinical cases of cowdriosis. (author)

  3. 77 FR 73827 - Endangered and Threatened Wildlife and Plants; Listing the Lesser Prairie-Chicken as a Threatened...

    Science.gov (United States)

    2012-12-11

    ... the lesser prairie-chicken (Tympanuchus pallidicinctus), a grassland bird known from southeastern... plants; wind energy development; petroleum production; and presence of roads and manmade vertical structures including towers, utility lines, fences, turbines, wells, and buildings. We will request peer...

  4. Forearc kinematics in obliquely convergent margins: Examples from Nicaragua and the northern Lesser Antilles

    Science.gov (United States)

    Turner, Henry L., III

    In this study, I use surface velocities derived from GPS geodesy, elastic half-space dislocation models, and modeled Coulomb stress changes to investigate deformation in the over-riding plate at obliquely convergent margins at the leading and trailing edges of the Caribbean plate. The two principal study areas are western Nicaragua, where the Cocos plate subducts beneath the Caribbean plate, and the northern Lesser Antilles, where the North American plate subducts beneath the Caribbean plate. In Nicaragua, plate convergence is rapid at 84 mm yr1 with a small angle of obliquity of 10° along a slightly concave portion of the Middle America Trench. GPS velocities for the period from 2000 to 2004 from sites located in the Nicaraguan forearc confirmed forearc sliver motion on the order of ˜14 mm yr1 in close agreement with the value predicted by DeMets (2001). These results are presented here in Chapter 3 and were reported in Geophysical Research Letters (Turner et al., 2007). GPS observations made on sites located in the interior and on the eastern coast of Nicaragua during the same time period were combined with new data from eastern Honduras to help better constrain estimates of rigid Caribbean plate motion (DeMets et al., 2007). Slip approaching the plate convergence rate along the Nicaraguan and El Salvadoran sections of the Middle America Trench was quantitatively demonstrated by finite element modeling of this section of the plate interface using GPS velocities from our Nicaraguan network together with velocities from El Salvador and Honduras as model constraints (Correa-Mora, 2009). The MW 6.9 earthquake that ruptured the seismogenic zone offshore Nicaragua on October 9, 2004 resulted in coseismic displacements and post-seismic motion at GPS sites in the central part of the Nicaraguan forearc that currently prevent extension of interseismic time-series in this region. An elastic half-space dislocation model was used to estimate coseismic displacements at these

  5. In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors.

    Science.gov (United States)

    Park, Jae B

    2017-12-13

    p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR) spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; -20 to -39) and several analogues with ΔE; -34 to -39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; -34 to -39) and in silico scores (Avg. score; -27.5 to -29.3). Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; -27.5 to -29.3) were found to inhibit p38 MAPK by 27-31% ( p silico score (Avg. score; -29.2) inhibited p38 MAPK (IC 50 = 9.9 μM) a little better than its methyl ester with best in silico score (Avg. score; -29.3). To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22-73% ( p silico and in vitro assay approach may be a useful and efficient solution as a functional screening approach in searching new lead compounds for targeted molecules.

  6. Activation of p44/42 MAPK plays a role in the TBT-induced loss of human natural killer (NK) cell function.

    Science.gov (United States)

    Dudimah, Fred D; Griffey, Denisha; Wang, Xiaofei; Whalen, Margaret M

    2010-10-01

    Natural killer (NK) cells destroy (lyse) tumor cells, virally infected cells, and antibody-coated cells. Previous studies indicated that exposure to the environmental contaminant tributyltin (TBT) decreases the lytic function of NK cells and activates mitogen-activated protein kinases (MAPK), including p44/42 (Aluoch and Whalen Toxicology 209:263-277, 2005). If activation of p44/42 is required for TBT-induced decreases of lytic function, then activation of p44/42 to similar extents by pharmacological agents such as phorbol 12-myristate 13-acetate (PMA) should mimic to some extent changes induced in NK cells with TBT exposures. NK cells were exposed to PMA concentrations between 0.25 and 10 nM for 10 min, 1 h, and 6 h before determining the lytic function ((51)Cr release assay) and phosphorylation state of MAPKs (Western blot). A 1-h exposure of NK cells to 5 nM PMA resulted in a loss of lytic function of 47%. Western blot analysis showed that a 1-h exposure to 5 nM PMA caused a sixfold increase in phospho-p44/42 levels. Previous studies showed a fivefold increase in phospho-p44/42 in response to a 1-h exposure to 300 nM TBT. Exposure to 300 nM TBT caused about a 40% decrease in lytic function. This study supports the hypothesis that p44/42 activation (as seen with TBT exposures) can cause a loss of NK-cell lytic function.

  7. Activation of p44/42 MAPK Plays a Role in the TBT-induced Loss of Human Natural Killer (NK) Cell Function

    Science.gov (United States)

    Dudimah, Fred D.; Griffey, Denisha; Wang, Xiaofei; Whalen, Margaret M.

    2009-01-01

    Natural Killer (NK) cells destroy (lyse) tumor cells, virally infected cells and antibody-coated cells. Previous studies indicated that exposure to the environmental contaminant tributyltin (TBT) decreases the lytic function of NK cells and activates mitogen activated protein kinases (MAPK), including p44/42 (Aluoch and Whalen, 2005). If activation of p44/42 is required for TBT-induced decreases of lytic function, then activation of p44/42 to similar extents by pharmacological agents such as Phorbol 12-myristate 13-acetate (PMA) should mimic to some extent changes induced in NK cells with TBT exposures. NK cells were exposed to PMA concentrations between 0.25 and 10 nM for 10 min, 1 h, and 6 h before determining the lytic function (51Cr release assay) and phosphorylation state of MAPKs (Western blot). A 1 h exposure of NK cells to 5 nM PMA resulted in a loss of lytic function of 47%. Western blot analysis showed that a 1 h exposure to 5 nM PMA caused a 6 fold increase in phospho-p44/42 levels. Previous studies showed a 5 fold increase in phospho-p44/42 in response to a 1 h exposure to 300 nM TBT. Exposure to 300 nM TBT caused about a 40% decrease in lytic function. This study supports the hypothesis that p44/42 activation (as seen with TBT exposures) can cause a loss of NK-cell lytic function. PMID:20213532

  8. Spatiotemporal distributions of intestinal helminths in female lesser scaup Aythya affinis during spring migration from the upper Midwest, USA.

    Science.gov (United States)

    England, J C; Levengood, J M; Osborn, J M; Yetter, A P; Kinsella, J M; Cole, R A; Suski, C D; Hagy, H M

    2017-07-01

    We examined the associations between intestinal helminth infracommunity structure and infection parameters and the age, size, and year and region of collection of 130 female lesser scaup (Aythya affinis) during their 2014-2015 spring migrations through the upper Midwest, USA. We identified a total of 647,174 individual helminths from 40 taxa, including 20 trematodes, 14 cestodes, 4 nematodes and 2 acanthocephalans parasitizing lesser scaup within the study area. Lesser scaup were each infected with 2-23 helminth taxa. One digenean, Plenosoma minimum, is reported for the first time in lesser scaup and in the Midwest. Mean trematode abundance and total helminth abundance was significantly less in 2015 than 2014, and we suspect that colder weather late in 2015 impacted the intermediate host fauna and caused the observed differences. Brillouin's species diversity of helminths was greatest in the northernmost region of the study area, which coincides with the range of a non-indigenous snail that indirectly causes annual mortality events of lesser scaup. While host age and size were not determined to be influential factors of helminth infracommunity structure, non-parametric ordination and permutational analysis of co-variance revealed that year and region of collection explained differences in helminth infracommunities. Our results suggest that spatiotemporal variations play an important role in the structure of intestinal helminth infracommunities found in migrating lesser scaup hosts, and may therefore impact host ability to build endogenous reserves at certain stopover locations in the Midwest.

  9. PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling.

    Science.gov (United States)

    Shrestha, Y; Schafer, E J; Boehm, J S; Thomas, S R; He, F; Du, J; Wang, S; Barretina, J; Weir, B A; Zhao, J J; Polyak, K; Golub, T R; Beroukhim, R; Hahn, W C

    2012-07-19

    Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK MAPK pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 30--33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.

  10. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigat...

  11. FGFR2c-mediated ERK-MAPK activity regulates coronal suture development

    Science.gov (United States)

    Pfaff, Miles J.; Xue, Ke; Li, Li; Horowitz, Mark C.; Steinbacher, Derek M.; Eswarakumar, Jacob V.P.

    2017-01-01

    Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor’s gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis. PMID:27034231

  12. Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer.

    Science.gov (United States)

    Grellety, Thomas; Gros, Audrey; Pedeutour, Florence; Merlio, Jean-Philippe; Duranton-Tanneur, Valerie; Italiano, Antoine; Soubeyran, Isabelle

    2016-10-01

    Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications.

  13. Proteomic and functional analyses reveal MAPK1 regulates milk protein synthesis.

    Science.gov (United States)

    Lu, Li-Min; Li, Qing-Zhang; Huang, Jian-Guo; Gao, Xue-Jun

    2012-12-27

    L-Lysine (L-Lys) is an essential amino acid that plays fundamental roles in protein synthesis. Many nuclear phosphorylated proteins such as Stat5 and mTOR regulate milk protein synthesis. However, the details of milk protein synthesis control at the transcript and translational levels are not well known. In this current study, a two-dimensional gel electrophoresis (2-DE)/MS-based proteomic technology was used to identify phosphoproteins responsible for milk protein synthesis in dairy cow mammary epithelial cells (DCMECs). The effect of L-Lys on DCMECs was analyzed by CASY technology and reversed phase high performance liquid chromatography (RP-HPLC). The results showed that cell proliferation ability and β-casein expression were enhanced in DCMECs treated with L-Lys. By phosphoproteomics analysis, six proteins, including MAPK1, were identified up-expressed in DCMECs treated with 1.2 mM L-Lys for 24 h, and were verified by quantitative real-time PCR (qRT-PCR) and western blot. Overexpression and siRNA inhibition of MAPK1 experiments showed that MAPK1 upregulated milk protein synthesis through Stat5 and mTOR pathway. These findings that MAPK1 involves in regulation of milk synthesis shed new insights for understanding the mechanisms of milk protein synthesis.

  14. ERK5 signaling gets XIAPed: a role for ubiquitin in the disassembly of a MAPK cascade

    Science.gov (United States)

    Klein, Aileen M; Cobb, Melanie H

    2014-01-01

    Mitogen-activated protein kinase (MAPK) cascades are tightly controlled through a series of well-characterized phospho-regulatory events. In this issue, Takeda et al (2014) identify the inhibitor of apoptosis protein, XIAP, as a key regulator of ERK5 activation via uncoupling of upstream kinase activity by non-degradative ubiquitination. PMID:25012518

  15. Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF-κB/MAPK signaling.

    Science.gov (United States)

    Mei, Xue; Wang, Hao-Xun; Li, Jian-Sheng; Liu, Xiao-Hui; Lu, Xiao-Fan; Li, Ya; Zhang, Wei-Yu; Tian, Yan-Ge

    2017-04-17

    Dusuqing granules (DSQ) have been used in the treatment of bacterial pneumonia clinically, with remarkable benefits. This study was initiated to explore the effects of DSQ on pulmonary inflammation by regulating nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signaling in bacterial pneumonia rats. Rat model was duplicated with Klebsiella pneumonia by a one-time intratracheal injection. Rats were randomized into control, model, DSQ and levofloxacin (LVX) groups. After administrated with appropriate medicines for 7 days, lung tissues were harvested and prepared for pathological analysis, and interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP)-1and macrophage inflammatory protein (MIP)-2 detections. NF-κB mRNA was measured by real-time qPCR, and the phosphorylation and total proteins of P38MAPK, JNK46/54, ERK42/44 were determined by Western blotting. Marked pathological impairments were observed in model rats, whereas were improved in DSQ group. The cytokines levels, NF-κB mRNA expression and the phosphorylation of P38MAPK, JNK46/54 and ERK42/44 proteins were significantly higher in model group, and were significantly depressed in DSQ group. The protective effects of DSQ on Klebsiella pneumonia might be attributed to its inactivative effects of NF-κB/ MAPK pathway.

  16. Regulation of mat responses by a differentiation MAPK pathway in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Sheelarani Karunanithi

    Full Text Available Fungal species exhibit diverse behaviors when presented with extracellular challenges. Pathogenic fungi can undergo cell differentiation and biofilm formation in response to fluctuating nutrient levels, and these responses are required for virulence. In the model fungal eukaryote Saccharomyces cerevisiae, nutrient limitation induces filamentous growth and biofilm/mat formation. Both responses require the same signal transduction (MAPK pathway and the same cell adhesion molecule (Flo11 but have been studied under different conditions. We found that filamentous growth and mat formation are aspects of a related response that is regulated by the MAPK pathway. Cells in yeast-form mats differentiated into pseudohyphae in response to nutrient limitation. The MAPK pathway regulated mat expansion (in the plane of the XY-axis and substrate invasion (downward in the plane of the Z-axis, which optimized the mat's response to extracellular nutrient levels. The MAPK pathway also regulated an upward growth pattern (in the plane of the Z-axis in response to nutrient limitation and changes in surface rigidity. Upward growth allowed for another level of mat responsiveness and resembled a type of colonial chemorepulsion. Together our results show that signaling pathways play critical roles in regulating social behaviors in which fungal cells participate. Signaling pathways may regulate similar processes in pathogens, whose highly nuanced responses are required for virulence.

  17. The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway

    NARCIS (Netherlands)

    D.A. Stevenson (David A.); L. Schill (Lisa); L. Schoyer (Lisa); B.S. Andresen (B.); A. Bakker (Annette); P. Bayrak-Toydemir (Pinar); E.M.M. Burkitt Wright (Emma M.); K. Chatfield (Kathryn); F. Elefteriou (Florent); Y. Elgersma (Ype); M.J. Fisher (Michael J.); D. Franz (David); B.D. Gelb (Bruce); A. Goriely (Anne); K.W. Gripp (Karen); A.Y. Hardan (Antonio Y.); K.M. Keppler-Noreuil (Kim M.); B. Kerr (Bronwyn); B. Korf (Bruce); C. Leoni (Chiara); F. Mccormick (Frank); S.R. Plotkin (Scott R.); K.A. Rauen (Katherine); K. Reilly (Karlyne); A.E. Roberts; A. Sandler (Abby); D. Siegel (Dawn); K.S. Walsh (Karin S.); B.C. Widemann (Brigitte C.)

    2016-01-01

    textabstractThe RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome,

  18. PKG-Mediated MAPK Signaling Is Necessary for Long-Term Operant Memory in "Aplysia"

    Science.gov (United States)

    Michel, Maximilian; Green, Charity L.; Eskin, Arnold; Lyons, Lisa C.

    2011-01-01

    Signaling pathways necessary for memory formation, such as the mitogen-activated protein kinase (MAPK) pathway, appear highly conserved across species and paradigms. Learning that food is inedible (LFI) represents a robust form of associative, operant learning that induces short- (STM) and long-term memory (LTM) in "Aplysia." We investigated the…

  19. Activation of MAPK Is Necessary for Long-Term Memory Consolidation Following Food-Reward Conditioning

    Science.gov (United States)

    Ribeiro, Maria J.; Schofield, Michael G.; Kemenes, Ildiko; O'Shea, Michael; Kemenes, Gyorgy; Benjamin, Paul R.

    2005-01-01

    Although an important role for the mitogen-activated protein kinase (MAPK) has been established for memory consolidation in a variety of learning paradigms, it is not known if this pathway is also involved in appetitive classical conditioning. We address this question by using a single-trial food-reward conditioning paradigm in the freshwater…

  20. Phosphofructokinase-P Modulates P44/42 MAPK Levels in HeLa Cells.

    Science.gov (United States)

    Cardim Pires, Thyago Rubens; Albanese, Jamille Mansur; Schwab, Michael; Marette, André; Carvalho, Renato Sampaio; Sola-Penna, Mauro; Zancan, Patricia

    2017-05-01

    It is known that interfering with glycolysis leads to profound modification of cancer cell proliferation. However, energy production is not the major reason for this correlation. Here, using HeLa cells as a model for cancer, we demonstrate that phosphofructokinase-P (PFK-P), which is overexpressed in diverse types of cancer including HeLa cells, modulates expression of P44/42 mitogen-activated protein kinase (MAPK). Silencing of PFK-P did not alter HeLa cell viability or energy production, including the glycolytic rate. On the other hand, silencing of PFK-P induced the downregulation of p44/42 MAPK, augmenting the sensitivity of HeLa cells to different drugs. Conversely, overexpression of PFK-P promotes the upregulation of p44/42 MAPK, making the cells more resistant to the drugs. These results indicate that overexpression of PFK-P by cancer cells is related to activation of survival pathways via upregulation of MAPK and suggest PFK-P as a promising target for cancer therapy. J. Cell. Biochem. 118: 1216-1226, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries

    DEFF Research Database (Denmark)

    Ansar, Saema; Eftekhari, Sajedeh; Waldsee, Roya

    2013-01-01

    if the upregulation of contractile cerebrovascular receptors after 48 h of organ culture of human cerebral arteries involves MAPK pathways and if it can be prevented by a MEK1/2 inhibitor. Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into ring...

  2. Ancient xenocrystic zircon in young volcanic rocks of the southern Lesser Antilles island arc

    Science.gov (United States)

    Rojas-Agramonte, Yamirka; Williams, Ian S.; Arculus, Richard; Kröner, Alfred; García-Casco, Antonio; Lázaro, Concepción; Buhre, Stephan; Wong, Jean; Geng, Helen; Echeverría, Carlos Morales; Jeffries, Teresa; Xie, Hangqian; Mertz-Kraus, Regina

    2017-10-01

    The Lesser Antilles arc is one of the best global examples in which to examine the effects of the involvement of subducted sediment and crustal assimilation in the generation of arc crust. Most of the zircon recovered in our study of igneous and volcaniclastic rocks from Grenada and Carriacou (part of the Grenadines chain) is younger than 2 Ma. Within some late Paleogene to Neogene ( 34-0.2 Ma) lavas and volcaniclastic sediments however, there are Paleozoic to Paleoarchean ( 250-3469 Ma) xenocrysts, and Late Jurassic to Precambrian zircon ( 158-2667 Ma) are found in beach and river sands. The trace element characteristics of zircon clearly differentiate between different types of magmas generated in the southern Lesser Antilles through time. The zircon population from the younger arc (Miocene, 22-19 Ma, to Present) has minor negative Eu anomalies, well-defined positive Ce anomalies, and a marked enrichment in heavy rare earth elements (HREE), consistent with crystallization from very oxidized magmas in which Eu2 + was in low abundance. In contrast, zircon from the older arc (Eocene to mid-Oligocene, 30-28 Ma) has two different REE patterns: 1) slight enrichment in the light (L)REE, small to absent Ce anomalies, and negative Eu anomalies and 2) enriched High (H)REE, positive Ce anomalies and negative Eu anomalies (a similar pattern is observed in the xenocrystic zircon population). The combination of positive Ce and negative Eu anomalies in the zircon population of the older arc indicates crystallization from magmas that were variably, but considerably less oxidized than those of the younger arc. All the igneous zircon has positive εHf(t), reflecting derivation from a predominantly juvenile mantle source. However, the εHf(t) values vary significantly within samples, reflecting considerable Hf isotopic heterogeneity in the source. The presence of xenocrystic zircon in the southern Lesser Antilles is evidence for the assimilation of intra-arc crustal sediments and

  3. A Proposed Community Network For Monitoring Volcanic Emissions In Saint Lucia, Lesser Antilles

    Science.gov (United States)

    Joseph, E. P.; Beckles, D. M.; Robertson, R. E.; Latchman, J. L.; Edwards, S.

    2013-12-01

    Systematic geochemical monitoring of volcanic systems in the English-speaking islands of the Lesser Antilles was initiated by the UWI Seismic Research Centre (SRC) in 2000, as part of its volcanic surveillance programme for the English-speaking islands of the Lesser Antilles. This programme provided the first time-series observations used for the purpose of volcano monitoring in Dominica and Saint Lucia, permitted the characterization of the geothermal fluids associated with them, and established baseline studies for understanding of the hydrothermal systems during periods of quiescence (Joseph et al., 2011; Joseph et al., 2013). As part of efforts to improve and expand the capacity of SRC to provide volcanic surveillance through its geothermal monitoring programme, it is necessary to develop economically sustainable options for the monitoring of volcanic emissions/pollutants. Towards this effort we intend to work in collaboration with local authorities in Saint Lucia, to develop a monitoring network for quantifying the background exposure levels of ambient concentrations of volcanic pollutants, SO2 in air and As in waters (as health significant marker elements in the geothermal emissions) that would serve as a model for the emissions monitoring network for other volcanic islands. This programme would facilitate the building of local capacity and training to monitor the hazardous exposure, through the application and transfer of a regionally available low-cost and low-technology SO2 measurement/detection system in Saint Lucia. Existing monitoring technologies to inform evidence based health practices are too costly for small island Caribbean states, and no government policies or health services measures currently exist to address/mitigate these influences. Gases, aerosols and toxic elements from eruptive and non-eruptive volcanic activity are known to adversely affect human health and the environment (Baxter, 2000; Zhang et al., 2008). Investigations into the

  4. Reproductive parameters of tropical lesser noddies respond to local variations in oceanographic conditions and weather

    Science.gov (United States)

    Monticelli, David; Ramos, Jaime A.; Catry, Teresa; Pedro, Patricia; Paiva, Vitor H.

    2014-02-01

    Most attempts to link seabirds and climate/oceanographic effects have concerned the Atlantic and Pacific Oceans with comparatively few studies in the tropical Indian Ocean. This paper examines the reproductive response of the lesser noddy Anous tenuirostris to temporal fluctuations in oceanographic and climatic conditions using 8 years of monitoring data from Aride Island (Seychelles), tropical Western Indian Ocean. We tested the hypothesis that breeding parameters (mean hatching date, mean egg size, hatching and fledging successes) and chick growth are influenced by local, seasonal oceanographic conditions as expressed by ocean primary productivity (surface chlorophyll-a concentrations; CC), sea surface temperature (SST) and wind speed. We also examined the relationship between lesser noddy breeding parameters and climate conditions recorded at the basin-wide scale of the Indian Ocean (Indian Ocean Dipole Mode Index, DMI). Our findings suggest that birds had a tendency to lay slightly larger eggs during breeding seasons (years) with higher CC during April-June (pre-laying, laying and incubation periods). Hatching date was positively related to SST in April-June, with the regression parameters suggesting that each 0.5 °C increase in SST meant a delay of approx.10 days in hatching date. A negative linear relationship was also apparent between hatching success and SST in June-August (hatching and chick-rearing periods), while the quadratic regression models detected a significant effect of wind speed in June-August on fledging success. Body mass increments of growing chicks averaged over 7-day periods were positively related with (2-week) lagged CC values and negatively related with (2-week) lagged SST values. No significant relationship between DMI and lesser noddy breeding parameters was found, but DMI indices were strongly correlated with local SST. Altogether, our results indicate that the reproduction of this top marine predator is dictated by fluctuations in

  5. Winter fidelity and apparent survival of lesser snow goose populations in the Pacific flyway

    Science.gov (United States)

    Williams, C.K.; Samuel, M.D.; Baranyuk, Vasily V.; Cooch, E.G.; Kraege, Donald K.

    2008-01-01

    The Beringia region of the Arctic contains 2 colonies of lesser snow geese (Chen caerulescens caerulescens) breeding on Wrangel Island, Russia, and Banks Island, Canada, and wintering in North America. The Wrangel Island population is composed of 2 subpopulations from a sympatric breeding colony but separate wintering areas, whereas the Banks Island population shares a sympatric wintering area in California, USA, with one of the Wrangel Island subpopulations. The Wrangel Island colony represents the last major snow goose population in Russia and has fluctuated considerably since 1970, whereas the Banks Island population has more than doubled. The reasons for these changes are unclear, but hypotheses include independent population demographics (survival and recruitment) and immigration and emigration among breeding or wintering populations. These demographic and movement patterns have important ecological and management implications for understanding goose population structure, harvest of admixed populations, and gene flow among populations with separate breeding or wintering areas. From 1993 to 1996, we neckbanded molting birds at their breeding colonies and resighted birds on the wintering grounds. We used multistate mark-recapture models to evaluate apparent survival rates, resighting rates, winter fidelity, and potential exchange among these populations. We also compared the utility of face stain in Wrangel Island breeding geese as a predictor of their wintering area. Our results showed similar apparent survival rates between subpopulations of Wrangel Island snow geese and lower apparent survival, but higher emigration, for the Banks Island birds. Males had lower apparent survival than females, most likely due to differences in neckband loss. Transition between wintering areas was low (exchange between the Banks and northern Wrangel Island populations. Face staining was an unreliable indicator of wintering area. Our findings suggest that northern and southern

  6. SlMAPK3 enhances tolerance to tomato yellow leaf curl virus (TYLCV) by regulating salicylic acid and jasmonic acid signaling in tomato (Solanum lycopersicum).

    Science.gov (United States)

    Li, Yunzhou; Qin, Lei; Zhao, Jingjing; Muhammad, Tayeb; Cao, Hehe; Li, Hailiang; Zhang, Yan; Liang, Yan

    2017-01-01

    Several recent studies have reported on the role of mitogen-activated protein kinase (MAPK3) in plant immune responses. However, little is known about how MAPK3 functions in tomato (Solanum lycopersicum L.) infected with tomato yellow leaf curl virus (TYLCV). There is also uncertainty about the connection between plant MAPK3 and the salicylic acid (SA) and jasmonic acid (JA) defense-signaling pathways. The results of this study indicated that SlMAPK3 participates in the antiviral response against TYLCV. Tomato seedlings were inoculated with TYLCV to investigate the possible roles of SlMAPK1, SlMAPK2, and SlMAPK3 against this virus. Inoculation with TYLCV strongly induced the expression and the activity of all three genes. Silencing of SlMAPK1, SlMAPK2, and SlMAPK3 reduced tolerance to TYLCV, increased leaf H2O2 concentrations, and attenuated expression of defense-related genes after TYLCV infection, especially in SlMAPK3-silenced plants. Exogenous SA and methyl jasmonic acid (MeJA) both significantly induced SlMAPK3 expression in tomato leaves. Over-expression of SlMAPK3 increased the transcript levels of SA/JA-mediated defense-related genes (PR1, PR1b/SlLapA, SlPI-I, and SlPI-II) and enhanced tolerance to TYLCV. After TYLCV inoculation, the leaves of SlMAPK3 over-expressed plants compared with wild type plants showed less H2O2 accumulation and greater superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activity. Overall, the results suggested that SlMAPK3 participates in the antiviral response of tomato to TYLCV, and that this process may be through either the SA or JA defense-signaling pathways.

  7. SlMAPK3 enhances tolerance to tomato yellow leaf curl virus (TYLCV by regulating salicylic acid and jasmonic acid signaling in tomato (Solanum lycopersicum.

    Directory of Open Access Journals (Sweden)

    Yunzhou Li

    Full Text Available Several recent studies have reported on the role of mitogen-activated protein kinase (MAPK3 in plant immune responses. However, little is known about how MAPK3 functions in tomato (Solanum lycopersicum L. infected with tomato yellow leaf curl virus (TYLCV. There is also uncertainty about the connection between plant MAPK3 and the salicylic acid (SA and jasmonic acid (JA defense-signaling pathways. The results of this study indicated that SlMAPK3 participates in the antiviral response against TYLCV. Tomato seedlings were inoculated with TYLCV to investigate the possible roles of SlMAPK1, SlMAPK2, and SlMAPK3 against this virus. Inoculation with TYLCV strongly induced the expression and the activity of all three genes. Silencing of SlMAPK1, SlMAPK2, and SlMAPK3 reduced tolerance to TYLCV, increased leaf H2O2 concentrations, and attenuated expression of defense-related genes after TYLCV infection, especially in SlMAPK3-silenced plants. Exogenous SA and methyl jasmonic acid (MeJA both significantly induced SlMAPK3 expression in tomato leaves. Over-expression of SlMAPK3 increased the transcript levels of SA/JA-mediated defense-related genes (PR1, PR1b/SlLapA, SlPI-I, and SlPI-II and enhanced tolerance to TYLCV. After TYLCV inoculation, the leaves of SlMAPK3 over-expressed plants compared with wild type plants showed less H2O2 accumulation and greater superoxide dismutase (SOD, peroxidase (POD, catalase (CAT, and ascorbate peroxidase (APX activity. Overall, the results suggested that SlMAPK3 participates in the antiviral response of tomato to TYLCV, and that this process may be through either the SA or JA defense-signaling pathways.

  8. Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells.

    Science.gov (United States)

    Seto-Young, D; Avtanski, D; Varadinova, M; Park, A; Suwandhi, P; Leiser, A; Parikh, G; Poretsky, L

    2011-06-01

    Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (pprogesterone production by 13-18% (pprogesterone production by 17-20% (pprogesterone production by 20-30% (pprogesterone production by 40-60% (pprogesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Triiodothyronine promotes the proliferation of epicardial progenitor cells through the MAPK/ERK pathway

    International Nuclear Information System (INIS)

    Deng, Song-Bai; Jing, Xiao-Dong; Wei, Xiao-ming; Du, Jian-Lin; Liu, Ya-Jie; Qin, Qin; She, Qiang

    2017-01-01

    Thyroid hormone has important functions in the development and physiological function of the heart. The aim of this study was to determine whether 3,5,3′-Triiodothyronine (T3) can promote the proliferation of epicardial progenitor cells (EPCs) and to investigate the potential underlying mechanism. Our results showed that T3 significantly promoted the proliferation of EPCs in a concentration- and time-dependent manner. The thyroid hormone nuclear receptor inhibitor bisphenol A (100 μmol/L) did not affect T3's ability to induce proliferation. Further studies showed that the mRNA expression levels of mitogen-activated protein kinase 1 (MAPK1), MAPK3, and Ki67 in EPCs in the T3 group (10 nmol/L) increased 2.9-, 3-, and 4.1-fold, respectively, compared with those in the control group (P < 0.05). In addition, the mRNA expression of the cell cycle protein cyclin D1 in the T3 group increased approximately 2-fold compared with the control group (P < 0.05), and there were more EPCs in the S phase of the cell cycle (20.6% vs. 12.0%, P < 0.05). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway inhibitor U0126 (10 μmol/L) significantly inhibited the ability of T3 to promote the proliferation of EPCs and to alter cell cycle progression. This study suggested that T3 significantly promotes the proliferation of EPCs, and this effect may be achieved through activation of the MAPK/ERK signaling pathway. - Highlights: • Epicardial progenitor cells were successfully cultured from E12.5 mice. • Thyroid hormone T3 significantly promoted the proliferation of EPCs. • This biological effect may be mediated via activation of the MAPK/ERK pathway.

  10. Role of the MAPKs/TGF-β1/TRAF6 signaling pathway in postoperative atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Daoliang Zhang

    Full Text Available To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD and its role in atrial fibrillation (AF after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis.A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF, respectively. Western blot was also used to measure the protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1. Serum angiotensin II (Ang II levels were assayed using enzyme-linked immunosorbent assay (ELISA.Eighteen patients developed AF, whereas 39 remained in sinus rhythm (SR. The severity of atrial fibrosis was significantly higher in patients who developed AF versus those who remained in SR; the mRNA and protein expression of TGF-β1, TRAF6 and CTGF were significantly higher in patients with AF. The protein expression of phosphorylated MAPKs and TAK1 was significantly increased in patients who developed AF compared with the patients who remained in SR. Serum Ang II levels were significantly higher in patients who developed AF versus those who remained in SR.The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis in patients with RHD, which results in the occurrence of AF after cardiac surgery.

  11. The Role of MAPK Modules and ABA during Abiotic Stress Signaling

    KAUST Repository

    Zélicourt, Axel de

    2016-05-01

    To respond to abiotic stresses, plants have developed specific mechanisms that allow them to rapidly perceive and respond to environmental changes. The phytohormone abscisic acid (ABA) was shown to be a pivotal regulator of abiotic stress responses in plants, triggering major changes in plant physiology. The ABA core signaling pathway largely relies on the activation of SnRK2 kinases to mediate several rapid responses, including gene regulation, stomatal closure, and plant growth modulation. Mitogen-activated protein kinases (MAPKs) have also been implicated in ABA signaling, but an entire ABA-activated MAPK module was uncovered only recently. In this review, we discuss the evidence for a role of MAPK modules in the context of different plant ABA signaling pathways. Abiotic stresses impact average yield in agriculture by more than 50% globally.Since ABA is a key regulator of abiotic stress responses, an understanding of its functioning at the molecular level is essential for plant breeding. Although the ABA core signaling pathway has been unraveled, several downstream events are still unclear.MAPKs are involved in most plant developmental stages and in response to stresses. Several members of the MAPK family were shown to be directly or indirectly activated by the ABA core signaling pathway.Recent evidence shows that the complete MAP3K17/18-MKK3-MPK1/2/7/14 module is under the control of ABA, whose members are under the transcriptional and post-translational control of the ABA core signaling pathway. © 2016 Elsevier Ltd.

  12. A virulent clone of Devriesea agamarum affects endangered Lesser Antillean iguanas (Iguana delicatissima).

    Science.gov (United States)

    Hellebuyck, Tom; Questel, Karl; Pasmans, Frank; Brantegem, Leen Van; Philip, Pascal; Martel, An

    2017-10-02

    Infectious diseases affecting wildlife are drivers of global biodiversity loss. Here we report a bacterial threat to endangered wild reptiles. Since April 2011, a severe skin disease has affected free-ranging, endangered Lesser Antillean iguanas (Iguana delicatissima) on the French Caribbean island of Saint Barthélemy and we identified Devriesea agamarum as the causative agent. The presence of this bacterium was also demonstrated in healthy lizards (anoles) co-inhabiting the island. All isolates from the iguanas corresponded to a single AFLP genotype that until now has exclusively been associated with infections in lizard species in captivity. The clonal relatedness of the isolates and recent emergence of the disease suggest recent arrival of a virulent D. agamarum clone on the island. The presence of healthy but infected lizards suggests the presence of asymptomatic reservoir hosts. This is the first description of a bacterial disease that poses a conservation threat towards free-ranging squamates.

  13. Assessments of the lesser sandeel ( Ammodytes marinus ) in the North Sea based on revised stock divisions

    DEFF Research Database (Denmark)

    Pedersen, S.A.; Lewy, Peter; Wright, P.

    1999-01-01

    effort, catch per unit effort, yield, fishing and natural mortality. A better understanding of sandeel growth is important for stock and catch predictions because previous studies indicate that the variability of mean weight-at-age is one of the most important factors influencing the precision......Recent investigations suggest that the current treatment of North Sea sandeel (Ammodytes marinus) as a single unit stock may have little biological basis. In order to study regional effects of the fishery on North Sea lesser sandeel it may therefore be important to assess stock dynamics...... of predictions. The Danish weight-at-age data of sandeel are re- analysed to estimate the mean weight-at-age in the catch and the stock and the precision of the estimates. The reliability of the sandeel assessments is discussed in relation to the data sources available and to the knowledge of sandeel biology...

  14. Reviewing host proteins of Rhabdoviridae: possible leads for lesser studied viruses.

    Science.gov (United States)

    Guleria, A; Kiranmayi, M; Sreejith, R; Kumar, K; Sharma, S K; Gupta, S

    2011-12-01

    Rhabdoviridae, characterized by bullet-shaped viruses, is known for its diverse host range, which includes plants, arthropods, fishes and humans. Understanding the viral-host interactions of this family can prove beneficial in developing effective therapeutic strategies. The host proteins interacting with animal rhabdoviruses have been reviewed in this report. Several important host proteins commonly interacting with animal rhabdoviruses are being reported, some of which, interestingly, have molecular features, which can serve as potential antiviral targets. This review not only provides the generalized importance of the functions of animal rhabdovirus-associated host proteins for the first time but also compares them among the two most studied viruses, i.e. Rabies virus (RV) and Vesicular Stomatitis virus (VSV). The comparative data can be used for studying emerging viruses such as Chandipura virus (CHPV) and the lesser studied viruses such as Piry virus (PIRYV) and Isfahan virus (ISFV) of the Rhabdoviridae family.

  15. A projection of lesser prairie chicken (Tympanuchus pallidicinctus) populations range-wide

    Science.gov (United States)

    Cummings, Jonathan W.; Converse, Sarah J.; Moore, Clinton T.; Smith, David R.; Nichols, Clay T.; Allan, Nathan L.; O'Meilia, Chris M.

    2017-08-09

    We built a population viability analysis (PVA) model to predict future population status of the lesser prairie-chicken (Tympanuchus pallidicinctus, LEPC) in four ecoregions across the species’ range. The model results will be used in the U.S. Fish and Wildlife Service's (FWS) Species Status Assessment (SSA) for the LEPC. Our stochastic projection model combined demographic rate estimates from previously published literature with demographic rate estimates that integrate the influence of climate conditions. This LEPC PVA projects declining populations with estimated population growth rates well below 1 in each ecoregion regardless of habitat or climate change. These results are consistent with estimates of LEPC population growth rates derived from other demographic process models. Although the absolute magnitude of the decline is unlikely to be as low as modeling tools indicate, several different lines of evidence suggest LEPC populations are declining.

  16. Reproductive biology of lesser spotted dogfish Scyliorhinus canicula (L., 1758 in the Cantabrian Sea

    Directory of Open Access Journals (Sweden)

    C. Rodríguez-Cabello

    1998-09-01

    Full Text Available This paper examines sexual maturity of the female lesser spotted dogfish Scyliorhinus canicula (L., 1758 in the Cantabrian Sea (north of Spain. Analyses made using data collected from commercial trawlers during 1994 and 1995 showed that females reach sexual maturity at a length of 54.2 cm, and the mean egg-laying size is 56.4 ± 0.94 cm. At least one in six adult female dogfish carried egg-capsules during the study period. Sex-ratio by depth strata indicates a larger proportion of females in deeper waters. Mature and spawning females were found at depths ranging from 100 m to more than 400 m, with their proportion being larger in the deeper strata.

  17. Contrasting sedimentary processes along a convergent margin: the Lesser Antilles arc system

    Science.gov (United States)

    Picard, Michel; Schneider, Jean-Luc; Boudon, Georges

    2006-12-01

    Sedimentation processes occurring in an active convergent setting are well illustrated in the Lesser Antilles island arc. The margin is related to westward subduction of the North and/or the South America plates beneath the Caribbean plate. From east to west, the arc can be subdivided into several tectono-sedimentary depositional domains: the accretionary prism, the fore-arc basin, the arc platform and inter-arc basin, and the Grenada back-arc basin. The Grenada back-arc basin, the fore-arc basin (Tobago Trough) and the accretionary prism on the east side of the volcanic arc constitute traps for particles derived from the arc platform and the South American continent. The arc is volcanically active, and provides large volumes of volcaniclastic sediments which accumulate mainly in the Grenada basin by volcaniclastic gravity flows (volcanic debris avalanches, debris flows, turbiditic flows) and minor amounts by fallout. By contrast, the eastern side of the margin is fed by ash fallout and minor volcaniclastic turbidites. In this area, the dominant component of the sediments is pelagic in origin, or derived from South America (siliciclastic turbidites). Insular shelves are the locations of carbonate sedimentation, such as large platforms which develop in the Limestone Caribbees in the northern part of the margin. Reworking of carbonate material by turbidity currents also delivers lesser amounts to eastern basins of the margin. This contrasting sedimentation on both sides of the arc platform along the margin is controlled by several interacting factors including basin morphology, volcanic productivity, wind and deep-sea current patterns, and sea-level changes. Basin morphology appears to be the most dominant factor. The western slopes of the arc platform are steeper than the eastern ones, thus favouring gravity flow processes.

  18. Mouse preimplantation embryo responses to culture medium osmolarity include increased expression of CCM2 and p38 MAPK activation

    Directory of Open Access Journals (Sweden)

    Watson Andrew J

    2007-01-01

    Full Text Available Abstract Background Mechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2. The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments. Results Our results indicate that Ccm2 along with upstream p38 MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4 are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels. Conclusion These results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.

  19. A cell-death-defying factor, anamorsin mediates cell growth through inactivation of PKC and p38MAPK

    International Nuclear Information System (INIS)

    Saito, Yuri; Shibayama, Hirohiko; Tanaka, Hirokazu; Tanimura, Akira; Kanakura, Yuzuru

    2011-01-01

    Research highlights: → Anamorsin (AM) (also called CIAPIN-1) is a cell-death-defying factor. → Biological mechanisms of AM functions have not been elucidated yet. → PKCθ , PKCδ and p38MAPK were more phosphorylated in AM deficient MEF cells. → AM may negatively regulates PKCs and p38MAPK in MEF cells. -- Abstract: Anamorsin (AM) plays crucial roles in hematopoiesis and embryogenesis. AM deficient (AM KO) mice die during late gestation; AM KO embryos are anemic and very small compared to wild type (WT) embryos. To determine which signaling pathways AM utilizes for these functions, we used murine embryonic fibroblast (MEF) cells generated from E-14.5 AM KO or WT embryos. Proliferation of AM KO MEF cells was markedly retarded, and PKCθ, PKCδ, and p38MAPK were more highly phosphorylated in AM KO MEF cells. Expression of cyclinD1, the target molecule of p38MAPK, was down-regulated in AM KO MEF cells. p38MAPK inhibitor as well as PKC inhibitor restored expression of cyclinD1 and cell growth in AM KO MEF cells. These data suggest that PKCθ, PKCδ, and p38MAPK activation lead to cell cycle retardation in AM KO MEF cells, and that AM may negatively regulate novel PKCs and p38MAPK in MEF cells.

  20. Chemical and sensory characteristics of frozen wheygurt with the addition of taro and lesser yam flours as thickening agent

    Science.gov (United States)

    Nurhartadi, E.; Utami, R.; Widowati, E.; Karunawati, B. M.

    2018-01-01

    Cheese whey is a waste product from cheese processing. It has low solid contents thus required the addition of a thickening agent. Lactic acid bacteria could utilize it in the fermented drink. This research aims to study the effect of taro and lesser yam flour addition as a thickening agent on chemical and sensory characteristics of frozen wheygurt. This research used Complete Randomized Design (CRD) with one factor that is variation ratio of taro and lesser yam flour F1 (4: 0), F2 (3: 1), F3 (2: 2), F4 (1: 3), F5 (0: 4). The number of lactic acid bacteria cell determined by using hemocytometer. The lactic acid content determined by the titrimetric method by using 0.1 N NaOH and phenolphthalein as indicator. pH value measured with pH meter. Sensory characteristics evaluated using hedonic test. The result showed that the addition of taro and lesser yam flour have a significant effect on the number of lactic acid bacteria in frozen wheygurt. The higher lesser yam flour addition, the higher lactic acid bacteria count on frozen wheygurt, due to lesser yam higher glucose and fructo-oligosaccharide content than taro. The higher lesser yam addition, the higher the lactic acid produced. The higher the total bacteria and higher levels of lactic acid, the lower the pH obtained. The conclusion of this study is addition ratio of taro and lesser yam flour effect on the chemical characteristics of frozen wheygurt. There is no difference in the level of acceptance of the panelists in sensory evaluation.

  1. A functional screen reveals an extensive layer of transcriptional and splicing control underlying RAS/MAPK signaling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dariel Ashton-Beaucage

    2014-03-01

    Full Text Available The small GTPase RAS is among the most prevalent oncogenes. The evolutionarily conserved RAF-MEK-MAPK module that lies downstream of RAS is one of the main conduits through which RAS transmits proliferative signals in normal and cancer cells. Genetic and biochemical studies conducted over the last two decades uncovered a small set of factors regulating RAS/MAPK signaling. Interestingly, most of these were found to control RAF activation, thus suggesting a central regulatory role for this event. Whether additional factors are required at this level or further downstream remains an open question. To obtain a comprehensive view of the elements functionally linked to the RAS/MAPK cascade, we used a quantitative assay in Drosophila S2 cells to conduct a genome-wide RNAi screen for factors impacting RAS-mediated MAPK activation. The screen led to the identification of 101 validated hits, including most of the previously known factors associated to this pathway. Epistasis experiments were then carried out on individual candidates to determine their position relative to core pathway components. While this revealed several new factors acting at different steps along the pathway--including a new protein complex modulating RAF activation--we found that most hits unexpectedly work downstream of MEK and specifically influence MAPK expression. These hits mainly consist of constitutive splicing factors and thereby suggest that splicing plays a specific role in establishing MAPK levels. We further characterized two representative members of this group and surprisingly found that they act by regulating mapk alternative splicing. This study provides an unprecedented assessment of the factors modulating RAS/MAPK signaling in Drosophila. In addition, it suggests that pathway output does not solely rely on classical signaling events, such as those controlling RAF activation, but also on the regulation of MAPK levels. Finally, it indicates that core splicing

  2. Intrinsic JNK-MAPK pathway involvement requires daf-16-mediated immune response during Shigella flexneri infection in C. elegans.

    Science.gov (United States)

    Marudhupandiyan, Shanmugam; Balamurugan, Krishnaswamy

    2017-06-01

    The c-Jun N-terminal kinase-mitogen-activated protein kinase (JNK-MAPK) pathway assists in modulating signals for growth, survival, and metabolism, thereby coordinating many cellular events during normal and stress conditions. To understand the role of the JNK-MAPK pathway during bacterial infection, an in vivo model organism Caenorhabditis elegans was used. In order to check the involvement of the JNK-MAPK pathway, the survival rate of C. elegans wild type (WT), and JNK-MAPK pathway mutant worms' upon exposure to selective Gram-positive and Gram-negative pathogenic bacteria, was studied. Among the pathogens, Shigella flexneri M9OT was found to efficiently colonize inside the WT and JNK-MAPK pathway mutant worms. qPCR studies had suggested that the above pathway-specific genes kgb-2 and jnk-1 were prominently responsible for the immune response elicited by the host during the M9OT infection. In addition, daf-16, which is a major transcription factor of the insulin/insulin growth factor-1 signaling (IIS) pathway, was also found to be involved during the host response. Crosstalk between IIS and JNK-MAPK pathways has probably been involved in the activation of the host immune system, which consequently leads to lifespan extension. Furthermore, it is also observed that daf-16 activation by JNK-MAPK pathway leads to antimicrobial response, by activating lys-7 expression. These findings suggest that JNK-MAPK is not the sole pathway that enhances the immunity of the host. Nonetheless, the IIS pathway bridges the JNK-MAPK pathway that influences in protecting the host in counter to the M9OT infection.

  3. Multisensor Analyzed Sea Ice Extent - Northern Hemisphere (MASIE-NH)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Multisensor Analyzed Sea Ice Extent Northern Hemisphere (MASIE-NH) products provide measurements of daily sea ice extent and sea ice edge boundary for the...

  4. Phosphorylation of mitogen-activated protein kinase (MAPK) is required for cytokinesis and progression of cell cycle in tobacco BY-2 cells.

    Science.gov (United States)

    Ma, Zhaowu; Yu, Guanghui

    2010-02-15

    The role of mitogen-activated protein kinase (MAPK) in plant cytokinesis remains largely uncharacterized. To elucidate its role, tobacco Bright Yellow-2 (BY-2) cells have been synchronized using a two-step procedure, and the different phases of the cell cycle identified by Histone 4 gene expression and the mitotic index. MAPK expression was analyzed by semi-quantitative (SQ) RT-PCR and protein gel blot analysis for phosphorylated MAPK during cell cycle progression. The SQ RT-PCR analysis indicated that MAPK expression is lower in mitosis than in interphase (G1, G2 and S). However, the amount of phosphorylated MAPK remained stable throughout the cell cycle, indicating that MAPK activity is predominantly regulated at the post-translational level and that phosphorylation of MAPK plays an important role in mitosis. Application of the specific MAPK phosphorylation inhibitor U0126 revealed that while U0126 treatment decreases the phosphorylation of MAPK and the progression from telophase to early cytokinesis is significantly inhibited. The formation of the phragmoplast is also negatively affected at this stage. These results demonstrate that MAPK phosphorylation is involved in the formation of the cell plate within the phragmoplast during cytokinesis and that MAPK predominantly functions during the cytokinesis stage of the cell cycle in tobacco BY-2 cells. Copyright 2009 Elsevier GmbH. All rights reserved.

  5. Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria.

    Directory of Open Access Journals (Sweden)

    Soledad Galli

    2008-06-01

    Full Text Available Mitochondria are major cellular sources of hydrogen peroxide (H(2O(2, the production of which is modulated by oxygen availability and the mitochondrial energy state. An increase of steady-state cell H(2O(2 concentration is able to control the transition from proliferating to quiescent phenotypes and to signal the end of proliferation; in tumor cells thereby, low H(2O(2 due to defective mitochondrial metabolism can contribute to sustain proliferation. Mitogen-activated protein kinases (MAPKs orchestrate signal transduction and recent data indicate that are present in mitochondria and regulated by the redox state. On these bases, we investigated the mechanistic connection of tumor mitochondrial dysfunction, H(2O(2 yield, and activation of MAPKs in LP07 murine tumor cells with confocal microscopy, in vivo imaging and directed mutagenesis. Two redox conditions were examined: low 1 microM H(2O(2 increased cell proliferation in ERK1/2-dependent manner whereas high 50 microM H(2O(2 arrested cell cycle by p38 and JNK1/2 activation. Regarding the experimental conditions as a three-compartment model (mitochondria, cytosol, and nuclei, the different responses depended on MAPKs preferential traffic to mitochondria, where a selective activation of either ERK1/2 or p38-JNK1/2 by co-localized upstream kinases (MAPKKs facilitated their further passage to nuclei. As assessed by mass spectra, MAPKs activation and efficient binding to cognate MAPKKs resulted from oxidation of conserved ERK1/2 or p38-JNK1/2 cysteine domains to sulfinic and sulfonic acids at a definite H(2O(2 level. Like this, high H(2O(2 or directed mutation of redox-sensitive ERK2 Cys(214 impeded binding to MEK1/2, caused ERK2 retention in mitochondria and restricted shuttle to nuclei. It is surmised that selective cysteine oxidations adjust the electrostatic forces that participate in a particular MAPK-MAPKK interaction. Considering that tumor mitochondria are dysfunctional, their inability to

  6. Long-distance multistep sediment transfer at convergent plate margins (Barbados, Lesser Antilles)

    Science.gov (United States)

    Limonta, Mara; Garzanti, Eduardo; Resentini, Alberto; Andò, Sergio; Boni, Maria; Bechstädt, Thilo

    2015-04-01

    We present a regional provenance study of the compositional variability and long distance multicyclic transport of terrigenous sediments along the convergent and transform plate boundaries of Central America, from the northern termination of the Andes to the Lesser Antilles arc-trench system. We focus on high-resolution bulk-petrography and heavy-mineral analyses of modern beach and fluvial sediments and Cenozoic sandstones of Barbados island, one of the places in the world where an active accretionary prism is subaerially exposed (Speed et al., 2012). The main source of siliciclastic sediment in the Barbados accretionary prism is off-scraped quartzose to feldspatho-litho-quartzose metasedimentaclastic turbidites, ultimately supplied from South America chiefly via the Orinoco fluvio-deltaic system. Modern sand on Barbados island is either quartzose with depleted heavy-mineral suites recycled from Cenozoic turbidites and including epidote, zircon, tourmaline, andalusite, garnet, staurolite and chloritoid, or calcareous and derived from Pleistocene coral reefs. The ubiquitous occurrence of clinopyroxene and hypersthene, associated with green-brown kaersutitic hornblende in the north or olivine in the south, points to reworking of ash-fall tephra erupted from andesitic (St. Lucia) and basaltic (St. Vincent) volcanic centers in the Lesser Antilles arc transported by the prevailing anti-trade winds in the upper troposphere. Modern sediments on Barbados island and those shed by other accretionary prisms such as the Indo- Burman Ranges and Andaman-Nicobar Ridge (Garzanti et al., 2013) define the distinctive mineralogical signature of Subduction Complex Provenance, which is invariably composite. Detritus recycled dominantly from accreted turbidites and oceanic mudrocks is mixed in various proportions with detritus from the adjacent volcanic arc or carbonate reefs widely developed at tropical latitudes. Ophiolitic detritus may be locally prominent. Quantitative provenance

  7. Multiscaling properties of tropical rainfall: Analysis of rain gauge datasets in Lesser Antilles island environment

    Science.gov (United States)

    Bernard, Didier C.; Pasquier, Raphaël; Cécé, Raphaël; Dorville, Jean-François

    2014-05-01

    Changes in rainfall seem to be the main impact of climate change in the Caribbean area. The last conclusions of IPCC (2013), indicate that the end of this century will be marked by a rise of extreme rainfalls in tropical areas, linked with increase of the mean surface temperature. Moreover, most of the Lesser Antilles islands are characterized by a complex topography which tends to enhance the rainfall from synoptic disturbances by orographic effects. In the past five years, out of hurricanes passage, several extreme rainy events (approx. 16 mm in 6 minutes), including fatal cases, occurred in the Lesser Antilles Arc: in Guadeloupe (January 2011, May 2012 and 2013), in Martinique (May 2009, April 2011 and 2013), in Saint-Lucia (December 2013). These phenomena inducing floods, loss of life and material damages (agriculture sector and public infrastructures), inhibit the development of the islands. At this time, numerical weather prediction models as WRF, which are based on the equations of the atmospheric physics, do not show great results in the focused area (Bernard et al., 2013). Statistical methods may be used to examine explicitly local rainy updrafts, thermally and orographically induced at micro-scale. The main goal of the present insular tropical study is to characterize the multifractal symmetries occurring in the 6-min rainfall time series, registered since 2006 by the French Met. Office network weather stations. The universal multifractal model (Schertzer and Lovejoy, 1991) is used to define the statistical properties of measured rainfalls at meso-scale and micro-scale. This model is parametrized by a fundamental exponents set (H,a,C1,q) which are determined and compared with values found in the literature. The first three parameters characterize the mean pattern and the last parameter q, the extreme pattern. The occurrence ranges of multifractal regime are examined. The suggested links between the internal variability of the tropical rainy events and the

  8. New Perspective of Tsunami Deposit Investigations: Insight from the 1755 Lisbon Tsunami in Martinique, Lesser Antilles.

    Science.gov (United States)

    Roger, J.; Clouard, V.; Moizan, E.

    2014-12-01

    The recent devastating tsunamis having occurred during the last decades have highlighted the essential necessity to deploy operationnal warning systems and educate coastal populations. This could not be prepared correctly without a minimum knowledge about the tsunami history. That is the case of the Lesser Antilles islands, where a few handfuls of tsunamis have been reported over the past 5 centuries, some of them leading to notable destructions and inundations. But the lack of accurate details for most of the historical tsunamis and the limited period during which we could find written information represents an important problem for tsunami hazard assessment in this region. Thus, it is of major necessity to try to find other evidences of past tsunamis by looking for sedimentary deposits. Unfortunately, island tropical environments do not seem to be the best places to keep such deposits burried. In fact, heavy rainfalls, storms, and all other phenomena leading to coastal erosion, and associated to human activities such as intensive sugarcane cultivation in coastal flat lands, could caused the loss of potential tsunami deposits. Lots of places have been accurately investigated within the Lesser Antilles (from Sainte-Lucia to the British Virgin Islands) the last 3 years and nothing convincing has been found. That is when archeaological investigations excavated a 8-cm thick sandy and shelly layer in downtown Fort-de-France (Martinique), wedged between two well-identified layers of human origin (Fig. 1), that we found new hope: this sandy layer has been quickly attributed without any doubt to the 1755 tsunami, using on one hand the information provided by historical reports of the construction sites, and on the other hand by numerical modeling of the tsunami (wave heights, velocity fields, etc.) showing the ability of this transoceanic tsunami to wrap around the island after ~7 hours of propagation, enter Fort-de-France's Bay with enough energy to carry sediments, and

  9. Numerical Tsunami Hazard Assessment of the Only Active Lesser Antilles Arc Submarine Volcano: Kick 'em Jenny.

    Science.gov (United States)

    Dondin, F. J. Y.; Dorville, J. F. M.; Robertson, R. E. A.

    2015-12-01

    The Lesser Antilles Volcanic Arc has potentially been hit by prehistorical regional tsunamis generated by voluminous volcanic landslides (volume > 1 km3) among the 53 events recognized so far. No field evidence of these tsunamis are found in the vincity of the sources. Such a scenario taking place nowadays would trigger hazardous tsunami waves bearing potentially catastrophic consequences for the closest islands and regional offshore oil platforms.Here we applied a complete hazard assessment method on the only active submarine volcano of the arc Kick 'em Jenny (KeJ). KeJ is the southernmost edifice with recognized associated volcanic landslide deposits. From the three identified landslide episodes one is associated with a collapse volume ca. 4.4 km3. Numerical simulations considering a single pulse collapse revealed that this episode would have produced a regional tsunami. An edifice current volume estimate is ca. 1.5 km3.Previous study exists in relationship to assessment of regional tsunami hazard related to shoreline surface elevation (run-up) in the case of a potential flank collapse scenario at KeJ. However this assessment was based on inferred volume of collapse material. We aim to firstly quantify potential initial volumes of collapse material using relative slope instability analysis (RSIA); secondly to assess first order run-ups and maximum inland inundation distance for Barbados and Trinidad and Tobago, i.e. two important economic centers of the Lesser Antilles. In this framework we present for seven geomechanical models tested in the RSIA step maps of critical failure surface associated with factor of stability (Fs) for twelve sectors of 30° each; then we introduce maps of expected potential run-ups (run-up × the probability of failure at a sector) at the shoreline.The RSIA evaluates critical potential failure surface associated with Fs <1 as compared to areas of deficit/surplus of mass/volume identified on the volcanic edifice using (VolcanoFit 2

  10. Hallux Valgus and Lesser Toe Deformities are Highly Heritable in Adult Men and Women: the Framingham Foot Study

    Science.gov (United States)

    Hannan, Marian T.; Menz, Hylton B.; Jordan, Joanne M.; Cupples, L. Adrienne; Cheng, Chia-Ho; Hsu, Yi-Hsiang

    2013-01-01

    Objective To estimate heritability of three common disorders affecting the forefoot: hallux valgus, lesser toe deformities and plantar forefoot soft tissue atrophy in adult Caucasian men and women. Methods Between 2002-2008, a trained examiner used a validated foot exam to document presence of hallux valgus, lesser toe deformities and plantar soft tissue atrophy in 2,446 adults from the Framingham Foot Study. Among these, 1,370 participants with available pedigree structure were included. Heritability (h2) was estimated using pedigree structures by Sequential Oligogenic Linkage Analysis Routines (SOLAR) package. Results were adjusted for age, sex and BMI. Results Mean age of participants was 66 years (range 39 to 99 years) and 57% were female. Prevalence of hallux valgus, lesser toe deformities and plantar soft tissue atrophy was 31%, 29.6% and 28.4%, respectively. Significant h2 was found for hallux valgus (0.29 ~ 0.89, depending on age and sex) and lesser toe deformity (0.49 ~ 0.90 depending on age and sex). The h2 for lesser toe deformity in men and women aged 70+ years was 0.65 (p= 9×10−7). Significant h2 was found for plantar soft tissue atrophy in men and women aged 70+ years (h2 = 0.37; p=3.8×10−3). Conclusion To our knowledge, these are the first findings of heritability of foot disorders in humans, and they confirm the widely-held view that hallux valgus and lesser toe deformities are highly heritable in European-descent Caucasian men and women, underscoring the importance of future work to identify genetic determinants of the underlying genetic susceptibility to these common foot disorders. PMID:23696165

  11. Coevolving MAPK and PID phosphosites indicate an ancient environmental control of PIN auxin transporters in land plants.

    Science.gov (United States)

    Dory, Magdalena; Hatzimasoura, Elizabeth; Kállai, Brigitta M; Nagy, Szilvia K; Jäger, Katalin; Darula, Zsuzsanna; Nádai, Tímea V; Mészáros, Tamás; López-Juez, Enrique; Barnabás, Beáta; Palme, Klaus; Bögre, László; Ditengou, Franck A; Dóczi, Róbert

    2018-01-01

    Plant growth flexibly adapts to environmental conditions, implying cross-talk between environmental signalling and developmental regulation. Here, we show that the PIN auxin efflux carrier family possesses three highly conserved putative mitogen-activated protein kinase (MAPK) sites adjacent to the phosphorylation sites of the well-characterised AGC kinase PINOID, which regulates the polar localisation of PINs and directional auxin transport, thereby underpinning organ growth. The conserved sites of PIN1 are phosphorylated in vitro by two environmentally activated MAPKs, MPK4 and MPK6. In contrast to AGC kinases, MAPK-mediated phosphorylation of PIN1 at adjacent sites leads to a partial loss of the plasma membrane localisation of PIN1. MAPK-mediated modulation of PIN trafficking may participate in environmental adjustment of plant growth. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  12. Convergence of Multiple MAP3Ks on MKK3 Identifies a Set of Novel Stress MAPK Modules

    KAUST Repository

    Colcombet, Jean

    2016-12-22

    Since its first description in 1995 and functional characterization 12 years later, plant MKK3-type MAP2Ks have emerged as important integrators in plant signaling. Although they have received less attention than the canonical stress-activated mitogen-activated protein kinases (MAPKs), several recent publications shed light on their important roles in plant adaptation to environmental conditions. Nevertheless, the MKK3-related literature is complicated. This review summarizes the current knowledge and discrepancies on MKK3 MAPK modules in plants and highlights the singular role of MKK3 in green plants. In the light of the latest data, we hypothesize a general model that all clade-III MAP3Ks converge on MKK3 and C-group MAPKs, thereby defining a set of novel MAPK modules which are activated by stresses and internal signals through the transcriptional regulation of MAP3K genes.

  13. In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors

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    Jae B. Park

    2017-12-01

    Full Text Available p38 Mitogen-activated protein kinase (p38 MAPK is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; −20 to −39 and several analogues with ΔE; −34 to −39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; −34 to −39 and in silico scores (Avg. score; −27.5 to −29.3. Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; −27.5 to −29.3 were found to inhibit p38 MAPK by 27–31% (p < 0.05 better than those with less scores (ΔE < −27.0. Especially, javamide-II-O-ethyl ester with relatively high in silico score (Avg. score; −29.2 inhibited p38 MAPK (IC50 = 9.9 μM a little better than its methyl ester with best in silico score (Avg. score; −29.3. To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22–73% (p < 0.05 in the differentiated THP-1 cells, and the inhibition was slightly stronger by the ethyl ester than the methyl ester. Altogether, this study suggests that javamide-II-O-ethyl ester may

  14. The mitogen-activated protein kinase (MAPK pathway: role in immune evasion by trypanosomatids

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    Mercedes Carolina Soares-Silva

    2016-02-01

    Full Text Available Leishmania spp and Trypanosoma cruzi are the causative agents of leishmaniasis and Chagas' disease, respectively, two neglected tropical diseases that affect about 25 million people worldwide. These parasites belong to the family Trypanosomatidae and are both obligate intracellular parasites that manipulate host signaling pathways to establish the infection, and also subvert the host innate immune system. Mitogen-activated protein kinases (MAPKs are serine and threonine protein kinases, highly conserved in eukaryotes, and are involved in signal transduction pathways that are related to modulation of physiological and pathophysiological cell responses. This mini-review highlights the current knowledge about the mechanisms that Leishmania spp and T. cruzi have evolved to target host MAPK signaling pathway, highjack immune response, and in this manner, promote parasite maintenance in the host.

  15. Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC γ 2-PKC and MAPK pathways.

    Science.gov (United States)

    Yen, Ting-Lin; Lu, Wan-Jung; Lien, Li-Ming; Thomas, Philip Aloysius; Lee, Tzu-Yin; Chiu, Hou-Chang; Sheu, Joen-Rong; Lin, Kuan-Hung

    2014-01-01

    Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60  μM) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC) γ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLC γ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

  16. Amarogentin, a Secoiridoid Glycoside, Abrogates Platelet Activation through PLCγ2-PKC and MAPK Pathways

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    Ting-Lin Yen

    2014-01-01

    Full Text Available Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60 μM inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (MAPKs. It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLCγ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

  17. Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

    KAUST Repository

    Frei dit Frey, Nicolas

    2014-06-30

    Background Mitogen-activated protein kinases (MAPKs) are key regulators of immune responses in animals and plants. In Arabidopsis, perception of microbe-associated molecular patterns (MAMPs) activates the MAPKs MPK3, MPK4 and MPK6. Increasing information depicts the molecular events activated by MAMPs in plants, but the specific and cooperative contributions of the MAPKs in these signalling events are largely unclear. Results In this work, we analyse the behaviour of MPK3, MPK4 and MPK6 mutants in early and late immune responses triggered by the MAMP flg22 from bacterial flagellin. A genome-wide transcriptome analysis reveals that 36% of the flg22-upregulated genes and 68% of the flg22-downregulated genes are affected in at least one MAPK mutant. So far MPK4 was considered as a negative regulator of immunity, whereas MPK3 and MPK6 were believed to play partially redundant positive functions in defence. Our work reveals that MPK4 is required for the regulation of approximately 50% of flg22-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76% of flg22-downregulated genes require two or three MAPKs for their regulation. The flg22-induced MAPK activities are differentially regulated in MPK3 and MPK6 mutants, both in amplitude and duration, revealing a highly interdependent network. Conclusions These data reveal a new set of distinct functions for MPK3, MPK4 and MPK6 and indicate that the plant immune signalling network is choreographed through the interplay of these three interwoven MAPK pathways.

  18. Forced copulation results in few extrapair fertilizations in Ross's and lesser snow geese

    Science.gov (United States)

    Dunn, P.O.; Afton, A.D.; Gloutney, M.L.; Alisauskas, R.T.

    1999-01-01

    Extrapair paternity varies from 0 to over 70% of young among various populations of birds. Comparative studies have suggested that this variation is related to nesting density, breeding synchrony and the proportion of extrapair copulations. We used minisatellite DNA fingerprinting to examine levels of extrapair paternity in Ross's geese, Chen rossi, and lesser snow geese, C. caerulescens c. (hereafter snow geese) nesting in the largest known goose colony in the world. These geese have one of the highest known percentages of extrapair copulation (46-56% of all attempted copulations), and all of these appeared to be forced. Among all successful copulations, 33 and 38% were extrapair in Ross's and snow geese, respectively. Despite the high percentage of extrapair copulations, extrapair paternity was low in both Ross's and snow geese (2-5% of young). Extrapair paternity was not related to nest density in either species. However, in snow geese, extrapair paternity was more likely to occur in nests of females that nested asynchronously, either early or late in the season. This is one of a few reported examples of a negative relationship between extrapair paternity and breeding synchrony. Extrapair young also tended to come from eggs laid later in the clutch. Although forced extrapair copulations appear to be a relatively inefficient reproductive tactic for males, they may provide a reproductive advantage for some males.

  19. Seasonal and daily variation of radon at 10 m depth in borehole, Garhwal Lesser Himalaya, India

    Energy Technology Data Exchange (ETDEWEB)

    Choubey, V.M., E-mail: vchoubey@wihg.res.i [Wadia Institute of Himalayan Geology, 33, General Mahadeo Singh Road, Dehradun-248001 (India); Arora, B.R. [Wadia Institute of Himalayan Geology, 33, General Mahadeo Singh Road, Dehradun-248001 (India); Barbosa, S.M. [University of Lisbon, IDL, Campo Grande, Edificio C8, 1749-016 Lisboa (Portugal); Kumar, Naresh; Kamra, Leena [Wadia Institute of Himalayan Geology, 33, General Mahadeo Singh Road, Dehradun-248001 (India)

    2011-07-15

    Mostly accepted and widely reported radon (Rn{sup 222}) measurements, a tool for earthquake precursor research, is a part of multi-parametric geophysical observation in the Garhwal Lesser Himalaya for earthquake related studies. Radon is being recorded continuously at an interval of 15 min at 10 m depth in a 68 m deep borehole. Three years high resolution 15 min data at 10 m depth shows a complex trend and has a strong seasonal effect along with some diurnal, semi-diurnal and multi-day recurring trends. A well-defined seasonal pattern is prominent with a high emanation in summer and low values in winter accounting for about a 30% decrease in count values in winter when the atmospheric temperature is very low at this station located 1.90 km above mean sea level. Diurnal, semi-diurnal and multi-day trends in this time-series are mainly observed during April-May and October-November. This is the period of spring and autumn when there is a high contrast in day-night atmospheric temperature. Hence the high fluctuation in Rn concentration is mainly caused by the temperature contrast between the air-column inside the borehole and the atmosphere above the earth's surface.

  20. Microbial dynamics during production of lesser mealworms (Alphitobius diaperinus) for human consumption at industrial scale.

    Science.gov (United States)

    Wynants, E; Crauwels, S; Verreth, C; Gianotten, N; Lievens, B; Claes, J; Van Campenhout, L

    2018-04-01

    In this study, the microbial dynamics during an industrial production cyle of lesser mealworms (Alphitobius diaperinus), sold for human consumption, were characterised. The microbial numbers as well as the microbial diversity were generally higher for the substrate, existing of remaining feed, faeces and exuviae, than for the larvae. Most of the species-level operational taxonomic units, identified using Illumina MiSeq sequencing, that were present in the feed were also detected in the larvae and vice versa. However, bacterial diversity decreased in the larvae during rearing. These results suggested that the feed is an important determinant of the insect bacterial community, but that some bacterial species show a competitive advantage inside the insect gut and become dominant. A blanching treatment of the larvae after harvest reduced most microbial counts, but the number of aerobic endospores remained at 4.0 log cfu/g. Whereas food pathogens Salmonella spp., Listeria monocytogenes, Bacillus cereus or coagulase-positive staphylococci were not detected in our study, fungal isolates corresponding to the genera Aspergillus and Fusarium were recovered. Therefore, it cannot be excluded that mycotoxins were present. The results of this study contribute to a better understanding of the microbial dynamics and food safety aspects during the production of edible insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Documentary-derived chronologies of rainfall variability in Antigua, Lesser Antilles, 1770–1890

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    A. J. Berland

    2013-06-01

    Full Text Available This paper presents the first extensive reconstruction of precipitation variability in the Lesser Antilles using historical documentary sources. Over 13 250 items of documentation pertaining to Antigua from the period 1769–1890 were consulted, including missionary, plantation and governmental papers as well as contemporary scholarly publications. Based on the predominant meteorological conditions observed throughout the island, each "rain-year" (December–November was assigned one of five classifications (very wet, wet, "normal", dry and very dry. Local weather references relating to seven plantations in central-eastern Antigua were grouped according to dry (December–April and wet seasons (May–November, each of which were also categorised in the aforementioned manner. Results comprise individual island-wide and central-eastern Antiguan chronologies of relative precipitation levels, spanning the rain-years 1769–70 to 1889–90 and 1769–70 to 1853–54 respectively. The former is compared with available instrumental data for the years 1870–1890. Significant dry phases are identified in the rain-years 1775–80, 1788–91, 1820–22, 1834–37, 1844–45, 1859–60, 1862–64, 1870–74 and 1881–82, while wet episodes were 1771–74, 1833–34, 1837–38, 1841–44, 1845–46 and 1878–81. Evidence for major wet and dry spells is presented and findings are evaluated within wider historical and palaeoclimatic contexts.

  2. Genetic Diversity in the Lesser Antilles and Its Implications for the Settlement of the Caribbean Basin.

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    Jada Benn Torres

    Full Text Available Historical discourses about the Caribbean often chronicle West African and European influence to the general neglect of indigenous people's contributions to the contemporary region. Consequently, demographic histories of Caribbean people prior to and after European contact are not well understood. Although archeological evidence suggests that the Lesser Antilles were populated in a series of northward and eastern migratory waves, many questions remain regarding the relationship of the Caribbean migrants to other indigenous people of South and Central America and changes to the demography of indigenous communities post-European contact. To explore these issues, we analyzed mitochondrial DNA and Y-chromosome diversity in 12 unrelated individuals from the First Peoples Community in Arima, Trinidad, and 43 unrelated Garifuna individuals residing in St. Vincent. In this community-sanctioned research, we detected maternal indigenous ancestry in 42% of the participants, with the remainder having haplotypes indicative of African and South Asian maternal ancestry. Analysis of Y-chromosome variation revealed paternal indigenous American ancestry indicated by the presence of haplogroup Q-M3 in 28% of the male participants from both communities, with the remainder possessing either African or European haplogroups. This finding is the first report of indigenous American paternal ancestry among indigenous populations in this region of the Caribbean. Overall, this study illustrates the role of the region's first peoples in shaping the genetic diversity seen in contemporary Caribbean populations.

  3. Characteristics of Sediment Transportation in Two Contrasting Oak Forested Watersheds in the Lesser Central Himalaya, India

    Science.gov (United States)

    Qazi, N. U. Q.; Bruijnzeel, S., Sr.; Rai, S. P., Sr.

    2015-12-01

    Sediment transfer from mountainous areas to lowland areas is one of the most important geomorphological processes globally with the bulk of the sediment yield from such areas typically deriving from mass wastage processes. This study presents monthly, seasonal and annual variations in sediment transport (both suspended load and bedload) as well as dissolved loads over three consecutive water years (2008-2011) for two small forested watersheds with contrasting levels of forest disturbance in the Lesser Himalaya of Northwest India. Seasonal and annual suspended sediment yields were strongly influenced by amounts of rainfall and streamflow and showed a 10-63 fold range between wet and dry years. Of the annual load, some 93% was produced on average during the monsoon season (June-September). Sediment production by the disturbed forest catchment was 1.9-fold (suspended sediment) to 5.9-fold (bedload) higher than that for the well-stocked forest catchment. By contrast, dissolved loads varied much less between years, seasons (although minimal during the dry summer season), and degree of forest disturbance. Total mechanical denudation rates were 1.6 times and 4.6 times larger than chemical denudation rates for the little disturbed and the heavily disturbed forest catchment, respectively whereas overall denudation rates were estimated at 0.69 and 1.04 mm per 1000 years, respectively.

  4. Microscopic aspects of electrosensory system on the partially euryhaline lesser guitarfish

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    BIANCA S. RANGEL

    2017-12-01

    Full Text Available ABSTRACT The electrosensory system on elasmobranchs consists of subcutaneous electroreceptor organs known as ampullae of Lorenzini. The present study investigated the ampullae of Lorenzini morphology of the lesser guitarfish Zapteryx brevirostris, using light microscopy and scanning electron microscopy. The pore number found in the ventral skin surface is much higher than that found in the dorsal portion, characteristic of species that inhabit the euphotic zone. Under light microscopy it was possible to observe that the wall canal consists of a single layer of squamous epithelial cells. The canal features distal expansion, where the ampullae are located with up to six alveoli. The sensory epithelium of ampullae is composed by cubic cells, with oval nucleus, restricted to the interior of the alveoli. With analysis the clusters under scanning electron microscopy, it was possible to observe the structure and the random arrangement of individual ampullae, canals and nerves. The distribution of dorsal and ventral pores and ampullae in Z. brevirostris resembled those of the same family. The number of alveoli per ampullae was similar to that found in euryhaline elasmobranchs species, suggesting that the morphological organization in Z. brevirostris is linked to its possible evolutionary transitory position among batoids.

  5. The lesser evil? Initiating a benzodiazepine prescription in general practice: a qualitative study on GPs' perspectives.

    Science.gov (United States)

    Anthierens, Sibyl; Habraken, Hilde; Petrovic, Mirko; Christiaens, Thierry

    2007-12-01

    Chronic benzodiazepine (BZD) use is widespread and linked with adverse effects. There is consensus concerning the importance of initiating BZD as a crucial moment. Nevertheless specific research in this field is lacking. This paper addresses the views of GPs on why they start prescribing BZDs to first-time users. Qualitative study with five focus groups analysed using a systematic content analysis. Regions of Ghent and Brussels in Belgium. A total of 35 general practitioners. The GPs' perspective on their initiating of BZD prescribing. GPs reported that they are cautious in initiating BZD usage. At the same time, GPs feel overwhelmed by the psychosocial problems of their patients. They show empathy by prescribing. They feel in certain situations there are no other solutions and they experience BZDs as the lesser evil. They admit to resorting to BZDs because of time restraint and lack of alternatives. GPs do not perceive the addictive nature of BZD consumption as a problem with first-time users. GPs do not specifically mention patients' demand as an element for starting. The main concern of GPs is to help the patient. GPs should be aware of the addictive nature of BZD even in low doses and a non-pharmacological approach should be seen as the best first approach. If GPs decide to prescribe a BZD they should make plain to the patient that the medication is only a "temporary" solution with clear agreements with regard to medication withdrawal.

  6. Wetland use and feeding by lesser scaup during spring migration across the upper Midwest, USA

    Science.gov (United States)

    Anteau, M.J.; Afton, A.D.

    2009-01-01

    Low food availability and forage quality and concomitant decreased lipid reserves of lesser scaup (Aythya affinis; hereafter scaup) during spring migration in the upper Midwest may partially explain reductions in the continental population of scaup. In springs 20042005, we examined wetland use and feeding activity of scaup on 356 randomly-selected wetlands within 6 regions in Iowa, Minnesota, and North Dakota. We examined wetland characteristics that favor high scaup use in 286 of these wetlands. We found that probabilities of wetland use and feeding by scaup increased with turbidity up to 45 and 30 NTU, respectively, but then declined at higher turbidity levels. Wetland use was positively correlated with size of open-water zone and amphipod densities, but was not correlated with chironomid densities. Feeding increased with amphipod density up to 26 m-3 and then declined at higher amphipod densities; scaup seemingly forage most efficiently at amphipod densities above 26 m -3. Wetland use was higher in North Dakota than in southern Minnesota and Iowa. Our results indicate that effective wetland restoration efforts to benefit scaup require maintaining abundant populations of amphipods (generally near 26 m-3 landscape geometric mean) in wetlands with large (> 500 m diameter) open-water zones throughout the upper Midwest, but especially within Iowa and southern Minnesota.

  7. Hydrologically complemented deterministic slope stability analysis in part of Indian Lesser Himalaya

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    John Mathew

    2016-09-01

    Full Text Available This study uses a deterministic approach to evaluate the factor of safety (FS of the terrain for different hydrological conditions, in part of Indian Lesser Himalaya. The results indicate sudden increase in the percentage unstable area from 7.5% to 13.8% for rainfall intensity variation from 50 to 100 mm/day. For the rainfall intensity of 15 August 2007 which caused many landslides in the study area, 18.5% of the total area was unstable and it increases to 21.7%, 23.5% and 24.7%, respectively, for rainfall intensities corresponding to 10, 25 and 50 year return periods. This increment stagnates at about 260 mm/day, making about 25% of the area unstable. Higher rainfall intensities make progressively gentler slopes unstable, but limited to 25 degrees of slope in this area. The area underlain by granitic gneiss showed 23.1% of area as unstable for 135 mm/day of rainfall intensity, and was followed by those areas underlain by amphibolite (16%, limestone (13.7% and quartzite (10.4%. Receiver operating characteristic (ROC curve analysis has given 84.2% accuracy for the model. Conversion of FS to failure probability through Z scores enables identification unstable or marginally unstable areas, for planning selective slope stabilization measures.

  8. Probabilistic hurricane-induced storm surge hazard assessment in Guadeloupe, Lesser Antilles

    Science.gov (United States)

    Krien, Y.; Dudon, B.; Roger, J.; Zahibo, N.

    2015-08-01

    Current storm surge hazard maps in the French West Indies are essentially based on simple statistical methods using limited historical data and early low-resolution models which do not take the effect of waves into account. In this paper, we infer new 100-year and 1000-year surge levels in Guadeloupe from the numerical modelling of storm surges induced by a large set of synthetic events that are in statistical agreement with features of historical hurricanes in the North Atlantic Basin between 1980 and 2011. Computations are performed using the wave-current coupled model ADCIRC-SWAN with high grid resolutions (up to 40-60 m) in the coastal and wave dissipation areas. This model is validated against observations during past events such as hurricane HUGO (1989). Results are generally found to be in reasonable agreement with past studies in areas where surge is essentially wind-driven, but found to differ significantly in coastal regions where the transfer of momentum from waves to the water column constitutes a non-negligible part of the total surge. The methodology, which can be applied to other islands in the Lesser Antilles, allows storm surge level maps to be obtained that can be of major interest for coastal planners and decision makers in terms of risk management.

  9. Theory of mind in children with 'lesser variants' of autism: a longitudinal study.

    Science.gov (United States)

    Serra, M; Loth, F L; van Geert, P L C; Hurkens, E; Minderaa, R B

    2002-10-01

    The study investigated the development of theory-of-mind (ToM) knowledge in children with lesser variants' of autism (PDD-NOS) over a period thought to be critical for ToM development (i.e., 3 to 5 years of age). The sample included 11 children with PDD-NOS; 23 normally developing children were included for cross-sectional comparison and 13 normally developing children for longitudinal comparison. The groups were comparable in verbal and non-verbal mental age. Two storybooks were used for repeated assessment of various aspects of the children's theory of mind: emotion recognition, the distinction between physical and mental entities, prediction of behaviour and emotions on the basis of desires and prediction of behaviour and emotions on the basis of beliefs. The results showed that the children with PDD-NOS had specific difficulties in understanding and predicting other people's emotions on the basis of situational cues, desires and beliefs. However, their ability to predict actions from beliefs and desires were relatively intact. Compared to the normally developing children, these children achieved lower levels of theory-of-mind knowledge, both at time of initial assessment and approximately 6 months later. The data suggest that the theory-of-mind development of children with PDD-NOS is both delayed and deviant. The growth pattem of theory-of-mind skills in children with PDD-NOS seemed to be qualitatively different from the growth pattern found in the group of normally developing children.

  10. Intercontinental gene flow among western arctic populations of Lesser Snow Geese

    Science.gov (United States)

    Shorey, Rainy I.; Scribner, Kim T.; Kanefsky, Jeannette; Samuel, Michael D.; Libants, Scot V.

    2011-01-01

    Quantifying the spatial genetic structure of highly vagile species of birds is important in predicting their degree of population demographic and genetic independence during changing environmental conditions, and in assessing their abundance and distribution. In the western Arctic, Lesser Snow Geese (Chen caerulescens caerulescens) provide an example useful for evaluating spatial population genetic structure and the relative contribution of male and female philopatry to breeding and wintering locales. We analyzed biparentally inherited microsatellite loci and maternally inherited mtDNA sequences from geese breeding at Wrangel Island (Russia) and Banks Island (Canada) to estimate gene flow among populations whose geographic overlap during breeding and winter differ. Significant differences in the frequencies of mtDNA haplotypes contrast with the homogeneity of allele frequencies for microsatellite loci. Coalescence simulations revealed high variability and asymmetry between males and females in rates and direction of gene flow between populations. Our results highlight the importance of wintering areas to demographic independence and spatial genetic structure of these populations. Male-mediated gene flow among the populations on northern Wrangel Island, southern Wrangel Island, and Banks Island has been substantial. A high rate of female-mediated gene flow from southern Wrangel Island to Banks Island suggests that population exchange can be achieved when populations winter in a common area. Conversely, when birds from different breeding populations do not share a common wintering area, the probability of population exchange is likely to be dramatically reduced.

  11. Raptor community composition in the Texas Southern High Plains lesser prairie-chicken range

    Science.gov (United States)

    Behney, A.C.; Boal, Clint W.; Whitlaw, Heather A.; Lucia, D.R.

    2012-01-01

    Predation can be a factor in preventing prey population growth and sustainability when prey populations are small and fragmented, and when predator density is unrelated to the density of the single prey species. We conducted monthly raptor surveys from February 2007 to May 2009 in adjacent areas of the Texas Southern High Plains (USA) that do and do not support lesser prairie-chickens (Tympanuchus pallidicinctus), a candidate for protection under the Endangered Species Act. During the summer period corresponding to prairie-chicken nesting and brood-rearing, Swainson's hawks (Buteo swainsoni) were the most abundant raptor. During the lekking and overwintering period, the raptor community was diverse, with northern harriers (Circus cyaneus) being the most abundant species. Raptor abundance peaked during the early autumn and was lowest during the spring. Utility poles were a significant predictor of raptor density at survey points and Swainson's hawks and all raptors, pooled, were found in greater densities in non-prairie-chicken habitat dominated by mesquite (Prosopis glandulosa). Avian predation risk on prairie-chickens, based on presence and abundance of raptors, appears to be greatest during winter when there is a more abundant and diverse raptor community, and in areas with utility poles.

  12. Isotopic composition of strontium in three basalt-andesite centers along the Lesser Antilles arc

    Science.gov (United States)

    Hedge, C.E.; Lewis, J.F.

    1971-01-01

    Si87/Sr86 ratios have been determined for lavas and py lastic rocks from three basalt-andesite centers along the Lesser Antilles arc-Mt. Misery on the island of St. Kitts, Soufriere on the island of St. Vincent, and Carriacou, an island of The Grenadines. The average Si87/Sr86 content of these rocks is 0.7038 for Mt. Misery, 0.7041 for Soufriere, and 0.7053 for Carriacou. All the Sr87/Sr86 values from each center are the same within analytical uncertainty (??0.0002). The constancy of strontium isotopic data within each center supports the hypothesis that basalts and andesites for each specific center investigated are generated from the same source - in agreement with petrographic and major- and minor-element data. Strontium isotopic compositions and elemental concentrations, particularly of strontium and nickel, indicate that this source was mantle peridotite and that the relationship between the respective basalts and andesites is probably fractional crystallization. ?? 1971 Springer-Verlag.

  13. Forage digestibility and intake by lesser snow geese: effects of dominance and resource heterogeneity

    Science.gov (United States)

    Hupp, Jerry W.; White, Robert G.; Sedinger, James S.; Robertson, Donna G.

    1996-01-01

    We measured forage intake, digestibility, and retention time for 11 free-ranging, human-imprinted lesser snow geese (Chen caerulescens caerulescens) as they consumed underground stembases of tall cotton-grass (Eriophorum angustifolium) on an arctic staging area in northeastern Alaska. Geese fed in small patches (x̄=21.5 m2) of forage that made up ≤3% of the study area and consisted of high-quality “aquatic graminoid” and intermediate-quality “wet sedge” vegetation types. Dominant geese spent more time feeding in aquatic graminoid areas (r=0.61), but less total time feeding and more time resting than subdominant geese. Subdominant geese were displaced to areas of wet sedge where cotton-grass was a smaller proportion of underground biomass. Geese metabolized an average of 48% of the organic matter in stembases and there was a positive correlation between dominance and organic matter metabolizability (r=0.61). Total mean retention time of forage was 1.37 h and dry matter intake was 14.3 g/h. Snow geese that stage on the coastal plain of the Beaufort Sea likely use an extensive area because they consume a large mass of forage and exploit habitats that are patchily distributed and make up a small percentage of the landscape. Individual variation in nutrient absorption may result from agonistic interactions in an environment where resources are heterogeneously distributed.

  14. Ultra-differentiation of Sperm Tail of Lesser Egyptian Jerboa, Jaculus jaculus (Family: Dipodidae

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    Osama M. Sarhan

    2016-01-01

    Full Text Available In the present study, events of sperm tail differentiation in Lesser Egyptian Jerboa, Jaculus jaculus were studied for the first time. Generally, stages of sperm tail differentiation are more or less similar to that described by other studies in other rodents. In the present species, special structures were observed. These structures include, first: the formation of a hollow large unit of microtubules that appears to surround the nuclear envelope at its equatorial plane. The manchette microtubules (MMs are re-oriented toward the longitudinal direction and attached along hollow large unit of microtubules. Second, the formation of perinuclear space filled with an electron-translucent substance surrounds the posterior third of the developing nucleus. Third, the nuclear fossa and the connecting piece were inserted in the ventrodorsal region of the nucleus. Fourth, the fibrous sheath (FS is formed of dextral spiral fibrous ribs. Finally, the sperm tail of the present species has a single outer FS, however, other rodents, having additional inner fibrous units, between the outer FS and the inner developing axoneme.

  15. Molecular detection of Anaplasma phagocytophilum DNA in the lesser horseshoe bat (Rhinolophus hipposideros) guano.

    Science.gov (United States)

    Afonso, E; Goydadin, A-C

    2018-05-30

    Although bats are increasingly recognised as potential reservoir hosts of human zoonotic pathogens, bacteria in bats are still poorly studied. To investigate the DNA faecal prevalence of the bacterium Anaplasma phagocytophilum, we sampled 23 lesser horseshoe bat (Rhinolophus hipposideros) maternity colonies located in buildings (churches, barns) in rural villages of eastern France. A total of 552 faecal samples were collected from 278 individuals. Anaplasma phagocytophilum DNA was detected in the faeces of 63 individuals (22.7%). Such high prevalence might suggest persistent infection in bats and/or a frequent consumption of insect preys carrying bacteria. Faecal DNA prevalence varied highly among colonies but was not related to the colony size. Faecal DNA prevalence was the highest in the Jura Department, where the density of ticks is known to be the highest across the study area. Because the sampled bats live in close proximity to humans, we discuss how concerning the presence of A. phagocytophilum DNA in bat guano is for humans frequenting places of worship that shelter bats. We also advocate future research to understand what a high faecal DNA prevalence in bat guano really implicates in terms of bacteria transmission.

  16. Endogenous contributions to egg protein formation in lesser scaup Aythya affinis

    Science.gov (United States)

    Cutting, Kyle A.; Hobson, Keith A.; Rotella, Jay J.; Warren, Jeffrey M.; Wainwright-de la Cruz, Susan E.; Takekawa, John Y.

    2011-01-01

    Lesser scaup Aythya affinis populations have declined throughout the North American continent for the last three decades. It has been hypothesized that the loss and degradation of staging habitats has resulted in reduced female body condition on the breeding grounds and a concomitant decline in productivity. We explored the importance of body (endogenous) reserves obtained prior to arrival on the breeding ground in egg protein formation in southwestern Montana during 2006–2008 using stable-carbon (δ13C) and nitrogen (δ15N) isotope analyses of scaup egg components, female tissue, and local prey items. From arrival on the breeding grounds through the egg-laying period, δ15N values of scaup red blood cells decreased while δ13C values became less variable; a pattern consistent with endogenous tissues equilibrating with local (freshwater) dietary sources. In 2006 and 2008, isotopic values for egg albumen and yolk protein indicated that most (>90%) protein used to produce these components was obtained on the breeding grounds. However, in 2007, a year with an exceptionally warm and dry spring, endogenous reserves contributed on average 41% of yolk and 29% of albumen. Results from this study suggest that female scaup can meet the protein needs of egg production largely from local dietary food sources. This highlights the importance of providing high-quality breeding habitats for scaup. Whether this pattern holds in areas with similar breeding season lengths but longer migration routes, such as those found in the western boreal forest, should be investigated.

  17. Abundance and density of lesser prairie-chickens and leks in Texas

    Science.gov (United States)

    Timmer, Jennifer M.; Butler, M.J.; Ballard, Warren; Boal, Clint W.; Whitlaw, Heather A.

    2013-01-01

    Lesser prairie-chickens (LEPCs; Tympanuchus pallidicinctus) have experienced population declines due to both direct and indirect habitat loss, including conversion of native rangeland to cropland and disturbance from energy development. Our objectives were to 1) determine the current density of LEPC leks and LEPCs within the Texas (USA) occupied range, including areas with high potential for wind-energy development; and 2) find new leks. To estimate lek and LEPC density, we employed a line-transect-based aerial survey method using a Robinson 22 helicopter to count leks. We surveyed 26,810.9 km of transect in the spring of 2010 and 2011 and we detected 96 leks. We estimated a density of 2.0 leks/100 km(2) (90% CI = 1.4-2.7 leks/100 km(2)) and 12.3 LEPCs/100 km(2) (90% CI = 8.5-17.9 LEPCs/100 km(2)) and an abundance of 293.6 leks (90% CI = 213.9-403.0 leks) and 1,822.4 LEPCs (90% CI = 1,253.7-2,649.1 LEPCs) for our sampling frame. Our best model indicated that lek size and lek type (AIC(c) wt = 0.235) influenced lek detectability. Lek detectability was greater for larger leks and natural leks versus man-made leks. Our statewide survey efforts provide wildlife managers and biologists with population estimates, new lek locations, and areas to target for monitoring and conservation.

  18. Electrophysiology and Innervation of the Photosensitive Epistellar Body in the Lesser Octopus Eledone cirrhosa.

    Science.gov (United States)

    Cobb, C S; Williamson, R

    1998-08-01

    The innervation and responses to light of the cephalopod epistellar body were investigated in preparations isolated from the stellate ganglia of the lesser or northern octopus, Eledone cirrhosa. Extracellular generator potentials in response to flashes of light were recorded from these photosensitive vesicles, with the amplitude of the response being found to be dependent upon the intensity of the flash and the level of ambient illumination. Intracellular recordings from photoreceptor cells of the epistellar body showed that they had resting potentials of about -49 +/- 7 mV (mean +/- SD, n = 43) and were depolarized by flashes of white, but not red (>650 nm) light. The evoked depolarization consisted of a transient component, followed by a steady plateau in which the amplitude of the depolarization was well correlated with the log of the stimulus intensity. The evoked depolarizations induced action potentials in the photoreceptor cells, with the frequency of firing being well correlated with the stimulus intensity. The morphologies of individual photoreceptor cells were visualized by intracellular injections of the fluorescent dye Lucifer yellow, and the path of the epistellar nerve across the stellate ganglion, into the pallial nerve, toward the brain was traced using the lipophilic dye Di-I. This pathway was confirmed physiologically by recording light-evoked responses from the cut end of the pallial nerve.

  19. The knowledge of the inhabitants of Lesser Poland about the profession of an occupational therapist

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    Żmudzińska Urszula Ż

    2017-12-01

    Full Text Available Introduction: A contemporary model of occupational therapy differs from the previous model which was common in Poland in previous years. Therefore, the opinions of the society concerning the profession of an occupational therapist are constantly changing. Material and methods: The research included 244 inhabitants of Lesser Poland aged between 25 and 65 employed in various professions. A questionnaire regarding occupational therapy and the profession and competences of occupational therapists was applied in the study. Results: The presented results show that the job of an occupational therapist is perceived as a needed profession both by individuals who underwent such therapy and those who did not use such services. Responses regarding competences and activities in the profession of an occupational therapist revealed differences in the opinions of the study participants. Conclusions: Taking into account only competences and activities of an occupational therapist, associations of the study participants reflected the knowledge of the model of therapy that existed before and was mainly devoted to occupational therapy workshops. The respondents would trust an occupational therapist both in adapting the house to their needs and in performing exercises connected with activities of daily living.

  20. Female reproductive tract of the lesser anteater (Tamandua tetradactyla, myrmecophagidae, Xenarthra). Anatomy and histology.

    Science.gov (United States)

    Rossi, L F; Luaces, J P; Marcos, H J Aldana; Cetica, P D; Gachen, G; Jimeno, G Pérez; Merani, M S

    2011-11-01

    The morphological and histological features of the unusual reproductive tract of the female lesser anteater, Tamandua tetradactyla (Myrmecophagidae, Xenarthra), are described for the first time. The present study aimed to establish the main similarities and differences between this species and other xenarthrans. The populations of this species are declining rapidly for a number of reasons and our study is relevant to diverse programs related to its conservation. Studies were carried out on five female genital tracts of adult specimens. Ovaries were ovoid, presenting a medulla completely surrounded by the cortex, differently from that described in other xenarthans. Like in Dasypus but different from all other armadillos studied, single oocyte follicles were observed and a simple the uterus. The uterovaginal canal connects the uterus with the urogenital sinus. The simple columnar epithelium of the uterovaginal canal ends abruptly at a septum which resembles a hymen, where the transitional epithelium of the urogenital sinus appears. This ancestral feature is shared with that of other armadillos, except Tolypeutes matacus, which has a true vagina. Characteristics of the reproductive tract and sperm morphology of other Xenarthra are comparatively discussed. These observations suggest that important reproductive features are shared between the family Myrmecophagidae and the genus Dasypus, a basal group in the phylogeny of Xenarthra. Copyright © 2011 Wiley-Liss, Inc.

  1. Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway

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    Lei Liu

    2015-07-01

    Full Text Available Background/Aims: Angiotensin II receptor blockers (ARBs have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF. Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Methods: Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT antibody. Western blot was used to analysis the protein expression of neurturin. Results: Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Conclusion: Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway.

  2. Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway.

    Science.gov (United States)

    Liu, Lei; Geng, Jianqiang; Zhao, Hongwei; Yun, Fengxiang; Wang, Xiaoyu; Yan, Sen; Ding, Xue; Li, Wenpeng; Wang, Dingyu; Li, Jianqiang; Pan, Zhenwei; Gong, Yongtai; Tan, Xiangyang; Li, Yue

    2015-01-01

    Angiotensin II receptor blockers (ARBs) have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF). Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II) and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT) antibody. Western blot was used to analysis the protein expression of neurturin. Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway. © 2015 S. Karger AG, Basel.

  3. Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway

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    Song Fu

    2018-02-01

    Full Text Available Resveratrol, a polyphenol found in various plants, including grapes, plums and peanuts has shown various medIRInal properties, including antioxidant, protection of cardiovascular disease and cancer risk. However, the effects of resveratrol on spinal cord reperfusion injury have not been investigated. Hence, the present study was designed to evaluate the effect of resveratrol on nitric oxide synthase (iNOS/p38MAPK signaling pathway and to elucidate its regulating effect on the protection of spinal cord injury. Spinal cord ischemia–reperfusion injury (IRI was performed by the infrarenal abdominal aorta with mini aneurysm clip model. The expressions of iNOS and p38MAPK and the levels of biochemical parameters, including nitrite/nitrate, malondialdehyde (MDA, advanced oxidation products (AOPP, reduced glutathione (GSH, superoxide dismutase (SOD and catalase (CAT were measured in control and experimental groups. IRI-induced rats treated with 10 mg/kg resveratrol protected spinal cord from ischemia injury as supported by improved biological parameters measured in spinal cord tissue homogenates. The resveratrol treatment significantly decreased the levels of plasma nitrite/nitrate, iNOS mRNA and protein expressions and phosphorylation of p38MAPK in IRI-induced rats. Further, IRI-produced free radicals were reduced by resveratrol treatment by increasing enzymatic and non-enzymatic antioxidant levels such as GSH, SOD and CAT. Taken together, administration of resveratrol protects the damage caused by spinal cord ischemia with potential mechanism of suppressing the activation of iNOS/p38MAPK pathway and subsequent reduction of oxidative stress due to IRI.

  4. Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

    International Nuclear Information System (INIS)

    Guo, Xianling; Zhang, Baihe; Wu, Mengchao; Wei, Lixin; Ma, Nannan; Wang, Jin; Song, Jianrui; Bu, Xinxin; Cheng, Yue; Sun, Kai; Xiong, Haiyan; Jiang, Guocheng

    2008-01-01

    Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary gastric adenocarcinoma. This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining. The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy. Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line

  5. Triiodothyronine promotes the proliferation of epicardial progenitor cells through the MAPK/ERK pathway.

    Science.gov (United States)

    Deng, Song-Bai; Jing, Xiao-Dong; Wei, Xiao-Ming; Du, Jian-Lin; Liu, Ya-Jie; Qin, Qin; She, Qiang

    2017-04-29

    Thyroid hormone has important functions in the development and physiological function of the heart. The aim of this study was to determine whether 3,5,3'-Triiodothyronine (T3) can promote the proliferation of epicardial progenitor cells (EPCs) and to investigate the potential underlying mechanism. Our results showed that T3 significantly promoted the proliferation of EPCs in a concentration- and time-dependent manner. The thyroid hormone nuclear receptor inhibitor bisphenol A (100 μmol/L) did not affect T3's ability to induce proliferation. Further studies showed that the mRNA expression levels of mitogen-activated protein kinase 1 (MAPK1), MAPK3, and Ki67 in EPCs in the T3 group (10 nmol/L) increased 2.9-, 3-, and 4.1-fold, respectively, compared with those in the control group (P < 0.05). In addition, the mRNA expression of the cell cycle protein cyclin D1 in the T3 group increased approximately 2-fold compared with the control group (P < 0.05), and there were more EPCs in the S phase of the cell cycle (20.6% vs. 12.0%, P < 0.05). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway inhibitor U0126 (10 μmol/L) significantly inhibited the ability of T3 to promote the proliferation of EPCs and to alter cell cycle progression. This study suggested that T3 significantly promotes the proliferation of EPCs, and this effect may be achieved through activation of the MAPK/ERK signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Knockdown of Heparanase Suppresses Invasion of Human Trophoblasts by Activating p38 MAPK Signaling Pathway

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    Guanglu Che

    2018-01-01

    Full Text Available Preeclampsia is a pregnancy-related disease with increasing maternal and perinatal morbidity and mortality worldwide. Defective trophoblast invasion is considered to be a major factor in the pathophysiological mechanism of preeclampsia. Heparanase, the only endo-β-glucuronidase in mammalian cells, has been shown to be abnormally expressed in the placenta of preeclampsia patients in our previous study. The biological role and potential mechanism of heparanase in trophoblasts remain unclear. In the present study, stably transfected HTR8/SVneo cell lines with heparanase overexpression or knockdown were constructed. The effect of heparanase on cellular proliferation, apoptosis, invasion, tube formation, and potential pathways in trophoblasts was explored. Our results showed that overexpression of heparanase promoted proliferation and invasion. Knockdown of heparanase suppressed proliferation, invasion, and tube formation but induced apoptosis. These findings reveal that downregulation of heparanase may contribute to defective placentation and plays a crucial role in the pathogenesis of preeclampsia. Furthermore, increased activation of p38 MAPK in heparanase-knockdown HTR8/SVneo cell was shown by MAPK pathway phosphorylation array and Western blotting assay. After pretreatment with 3 specific p38 MAPK inhibitors (BMS582949, SB203580, or BIRB796, inadequate invasion in heparanase-knockdown HTR8/SVneo cell was rescued. That indicates that knockdown of heparanase decreases HTR8/SVneo cell invasion through excessive activation of the p38 MAPK signaling pathway. Our study suggests that heparanase can be a potential predictive biomarker for preeclampsia at an early stage of pregnancy and represents a promising therapeutic target for the treatment of preeclampsia.

  7. Integrative modelling of the influence of MAPK network on cancer cell fate decision.

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    Luca Grieco

    2013-10-01

    Full Text Available The Mitogen-Activated Protein Kinase (MAPK network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3 activating mutations.

  8. Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Huijuan; Tan, Shi; Wang, Juan; Chen, Shana; Quan, Jing; Xian, Jingrong; Zhang, Shuai shuai; He, Jingang; Zhang, Ling, E-mail: lingzhang@cqmu.edu.cn

    2014-01-01

    The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator within a variety of stem cell populations via the regulation of translational gene expression. A recent study has suggested that Msi2 is strongly expressed in leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is associated with poor prognosis. However, the potential role of Msi2 in leukemogenesis is still not well understood. Here, we investigated the effect of Msi2 knockdown on the biological properties of leukemic cells. High expression of Msi2 was found in K562 and KG-1a leukemic cell lines, and low expression was observed in the U937 cell line. We transduced K562 cells with two independent adenoviral shRNA vectors targeting Msi2 and confirmed knockdown of Msi2 at the mRNA and protein levels. Msi2 silencing inhibited cell growth and caused cell cycle arrest by increasing the expression of p21 and decreasing the expression of cyclin D1 and cdk2. In addition, knockdown of Msi2 promoted cellular apoptosis via the upregulation of Bax and downregulation of Bcl-2 expression. Furthermore, Msi2 knockdown resulted in the inactivation of the ERK/MAPK and p38/MAPK pathways, but no remarkable change in p-AKT was observed. These data provide evidence that Msi2 plays an important role in leukemogenesis involving the MAPK signaling pathway, which indicates that Msi2 may be a novel target for leukemia treatment. - Highlights: • Knockdown of Msi2 inhibited K562 cell growth and arrested cell cycle progression. • Knockdown of Msi2 induced K562 cell apoptosis via the regulation of Bax and Bcl-2. • The MAPK pathway was involved in the process of Msi2-mediated leukemogenesis. • Our data indicate that Msi2 is a potential new target for leukemia treatment.

  9. P38 mitogen-activated protein kinase (p38 MAPK) overexpression in clinical staging of nasopharyngeal carcinoma

    Science.gov (United States)

    Farhat; Asnir, R. A.; Yudhistira, A.; Daulay, E. R.; Muzakkir, M. M.; Yulius, S.

    2018-03-01

    Molecular biological research on nasopharyngeal carcinoma has been widely practiced, such as VEGF, EGFR, COX-2 expression and so on. MAPK plays a role in cell growth such as proliferation, differentiation, and apoptosis, primarily contributing to gene expression, where p38 MAPK pathway mostly associate with anti-apoptosis and cause cell transformation. The aim of this study is to determine the expression of p38 MAPK in clinical stage of nasopharyngeal carcinoma so that the result can be helpful in prognosis and adjunctive therapy in nasopharyngeal carcinoma. The research design is descriptive. It was done in THT- KL Department of FK USU/RSUP Haji Adam Malik, Medan and Pathology Anatomical Department of FK USU. The study was conducted from December 2011 to May 2012. The Samples are all patients who diagnosed with nasopharyngeal carcinoma in oncology division of Otorhinolaryngology Department. p38 MAPK overexpression was found in 21 samples (70%) from 30 nasopharyngeal carcinoma samples. The elevated of p38 MAPK expression most found on T4 by eight samples (38.1%), N3 lymph node group by nine samples (42.9%), stage IV of clinical staging is as many as 15 samples (71.4%). p38 MAPK most expressed in stage IV clinical staging of patients with nasopharyngeal carcinoma.

  10. Trihydrophobin 1 Phosphorylation by c-Src Regulates MAPK/ERK Signaling and Cell Migration

    Science.gov (United States)

    Wu, Weibin; Sun, Zhichao; Wu, Jingwen; Peng, Xiaomin; Gan, Huacheng; Zhang, Chunyi; Ji, Lingling; Xie, Jianhui; Zhu, Haiyan; Ren, Shifang

    2012-01-01

    c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src. PMID:22238675

  11. Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.

    Science.gov (United States)

    Li, Qing-chun; Liang, Yun; Tian, Yuan; Hu, Guang-rui

    2016-01-01

    In the current study the antiproliferative effect of arctigenin, plant lignin, was evaluated on human colon cancer cell line HT-29. Furthermore, attempts were made to explore the signaling mechanism which may be responsible for its effect. Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line. MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure. Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.

  12. Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580.

    Science.gov (United States)

    Fu, Yilong; Yip, Andy; Seah, Peck Gee; Blasco, Francesca; Shi, Pei-Yong; Hervé, Maxime

    2014-10-01

    Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-α, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Tributyltin induces disruption of microfilament in HL7702 cells via MAPK-mediated hyperphosphorylation of VASP.

    Science.gov (United States)

    Tu, Wei-Wei; Ji, Lin-Dan; Qian, Hai-Xia; Zhou, Mi; Zhao, Jin-Shun; Xu, Jin

    2016-11-01

    Tributyltin (TBT) has been widely used for various industrial purposes, and it has toxic effects on multiple organs and tissues. Previous studies have found that TBT could induce cytoskeletal disruption, especially of the actin filaments. However, the underlying mechanisms remain unclear. The aim of the present study was to determine whether TBT could induce microfilament disruption using HL7702 cells and then to assess for the total levels of various microfilament-associated proteins; finally, the involvement of the MAPK pathway was investigated. The results showed that after TBT treatment, F-actin began to depolymerize and lost its characteristic filamentous structure. The protein levels of Ezrin and Cofilin remained unchanged, the actin-related protein (ARP) 2/3 levels decreased slightly, and the vasodilator-stimulated phosphoprotein (VASP) decreased dramatically. However, the phosphorylation levels of VASP increased 2.5-fold, and the ratio of phosphorylated-VASP/unphosphorylated-VASP increased 31-fold. The mitogen-activated protein kinases (MAPKs) ERK and JNK were discovered to be activated. Inhibition of ERK and JNK not only largely diminished the TBT-induced hyperphosphorylation of VASP but also recovered the cellular morphology and rescued the cells from death. In summary, this study demonstrates that TBT-induced disruption of actin filaments is caused by the hyperphosphorylation of VASP through MAPK pathways. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1530-1538, 2016. © 2015 Wiley Periodicals, Inc.

  14. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shi, T.; Niepel, M.; McDermott, J. E.; Gao, Y.; Nicora, C. D.; Chrisler, W. B.; Markillie, L. M.; Petyuk, V. A.; Smith, R. D.; Rodland, K. D.; Sorger, P. K.; Qian, W. -J.; Wiley, H. S.

    2016-07-12

    It is not known whether cancer cells generally show quantitative differences in the expression of signaling pathway proteins that could dysregulate signal transduction. To explore this issue, we first defined the primary components of the EGF-MAPK pathway in normal human mammary epithelial cells, identifying 16 core proteins and 10 feedback regulators. We then quantified their absolute abundance across a panel of normal and cancer cell lines. We found that core pathway proteins were expressed at very similar levels across all cell types. In contrast, the EGFR and transcriptionally controlled feedback regulators were expressed at highly variable levels. The absolute abundance of most core pathway proteins was between 50,000- 70,000 copies per cell, but the adaptors SOS1, SOS2, and GAB1 were found at far lower levels (2,000-5,000 per cell). MAPK signaling showed saturation in all cells between 3,000-10,000 occupied EGFR, consistent with the idea that low adaptor levels limit signaling. Our results suggest that the core MAPK pathway is essentially invariant across different cell types, with cell- specific differences in signaling likely due to variable levels of feedback regulators. The low abundance of adaptors relative to the EGFR could be responsible for previous observation of saturable signaling, endocytosis, and high affinity EGFR.

  15. Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

    Science.gov (United States)

    Merlini, Laura

    2016-01-01

    Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone–GPCR (G-protein-coupled receptor)–MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell–cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception. PMID:27798845

  16. Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation.

    Science.gov (United States)

    Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Chen, Shih-Ann; Chen, Yi-Jen

    2013-06-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10μg/ml, 5-7h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n=25), collagen-treated PV cardiomyocytes (n=22) had a faster beating rate (3.2±04 vs. 1.9±0.2Hz, pcollagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca(2+)-activated K(+) current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. MAPK Phosphatase-1 Deficiency Exacerbates the Severity of Imiquimod-Induced Psoriasiform Skin Disease

    Directory of Open Access Journals (Sweden)

    Weiheng Zhao

    2018-03-01

    Full Text Available Persistent activation of mitogen-activated protein kinase (MAPK is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1 is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1−/− mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines. MKP-1 acted on both hematopoietic and non-hematopoietic cells to regulate psoriasis pathogenesis. MKP-1 deficiency in macrophages led to enhanced p38 activation and higher expression of interleukin (IL-1β, CXCL2, and S100a8 upon R848 stimulation. Moreover, MKP-1 deficiency in the non-hematopoietic compartments led to an enhanced IL-22 receptor signaling and higher expression of CXCL1 and CXCL2 upon IMQ treatment. Collectively, our data suggest a critical role for MKP-1 in the regulation of skin inflammation.

  18. Use of p38 MAPK Inhibitors for the Treatment of Werner Syndrome

    Directory of Open Access Journals (Sweden)

    Mark C. Bagley

    2010-06-01

    Full Text Available Werner syndrome provides a convincing model for aspects of the normal ageing phenotype and may provide a suitable model for therapeutic interventions designed to combat the ageing process. Cultured primary fibroblast cells from Werner syndrome patients provide a powerful model system to study the link between replicative senescence in vitro and in vivo pathophysiology. Genome instability, together with an increased pro-oxidant state, and frequent replication fork stalling, all provide plausible triggers for intracellular stress in Werner syndrome cells, and implicates p38 MAPK signaling in their shortened replicative lifespan. A number of different p38 MAPK inhibitor chemotypes have been prepared rapidly and efficiently using microwave heating techniques for biological study in Werner syndrome cells, including SB203580, VX-745, RO3201195, UR-13756 and BIRB 796, and their selectivity and potency evaluated in this cellular context. Werner syndrome fibroblasts treated with a p38 MAPK inhibitor reveal an unexpected reversal of the accelerated ageing phenotype. Thus the study of p38 inhibition and its effect upon Werner pathophysiology is likely to provide new revelations into the biological mechanisms operating in cellular senescence and human ageing in the future.

  19. Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms.

    Science.gov (United States)

    Tartaglia, Marco; Gelb, Bruce D

    2010-12-01

    RAS GTPases control a major signaling network implicated in several cellular functions, including cell fate determination, proliferation, survival, differentiation, migration, and senescence. Within this network, signal flow through the RAF-MEK-ERK pathway-the first identified mitogen-associated protein kinase (MAPK) cascade-mediates early and late developmental processes controlling morphology determination, organogenesis, synaptic plasticity, and growth. Signaling through the RAS-MAPK cascade is tightly controlled; and its enhanced activation represents a well-known event in oncogenesis. Unexpectedly, in the past few years, inherited dysregulation of this pathway has been recognized as the cause underlying a group of clinically related disorders sharing facial dysmorphism, cardiac defects, reduced postnatal growth, ectodermal anomalies, variable cognitive deficits, and susceptibility to certain malignancies as major features. These disorders are caused by heterozygosity for mutations in genes encoding RAS proteins, regulators of RAS function, modulators of RAS interaction with effectors, or downstream signal transducers. Here, we provide an overview of the phenotypic spectrum associated with germline mutations perturbing RAS-MAPK signaling, the unpredicted molecular mechanisms converging toward the dysregulation of this signaling cascade, and major genotype-phenotype correlations. © 2010 New York Academy of Sciences.

  20. ZNF383, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling pathway

    International Nuclear Information System (INIS)

    Cao Lei; Wang Zhi; Zhu Chuanbing; Zhao Yulian; Yuan Wuzhou; Li Jing; Wang Yuequn; Ying Zhaochu; Li Yongqing; Yu Weishi; Wu Xiushan; Liu Mingyao

    2005-01-01

    Mitogen-activated protein kinases (MAPKs) are major components of pathways controlling embryogenesis, cell differentiation, cell proliferation, and cell death. One of the most explored functions of MAPK signaling is the regulation of gene expression by direct or indirect phosphorylation and subsequent activation of transcription factors. In this article, we isolated a novel KRAB-related zinc finger gene named ZNF383 from an early embryo heart cDNA library. The cDNA of ZNF383 is 2220 bp, encoding a protein of 475 amino acids. The protein is conserved in evolution across different species. Northern blot analysis indicates that a 2.2 kb transcript specific for ZNF383 is detected in most of the examined human adult and embryonic tissues with a higher level in skeletal muscle. In COS-7 cells, ZNF383 protein is localized to nucleus and cytoplasm. ZNF383 is a transcription repressor when fused to Gal-4 DNA-binding domain and cotransfected with VP-16. Deletion analysis indicates that the KRAB box of ZNF383 is responsible for the transcriptional repressor activity. Overexpression of ZNF383 in cells inhibits the transcriptional activities of AP-1 and SRE, suggesting that ZNF383 may act as a negative regulator in MAPK-mediated signaling pathways

  1. Contaminated Larval and Adult Lesser Mealworms, Alphitobius diaperinus (Coleoptera: Tenebrionidae)can Transmit Salmonella Typhimurium in a Broiler Flock

    Science.gov (United States)

    The ability of the lesser mealworm, Alphitobius diaperinus (Panzer), commonly known as the darkling beetle, to transmit a marker strain Salmonella Typhimurium to day-of-hatch broiler chicks was evaluated, as well as the spread to non-challenged pen mates. Day-of-hatch chicks were orally gavaged wit...

  2. Synergistic effects of chlorpyrifos with piperonyl butoxide (pbo against the lesser mealworm, Alphitobius diaperinus (Panzer (Coleoptera: Tenebrionidae

    Directory of Open Access Journals (Sweden)

    Akter Mst Yeasmin

    2014-12-01

    Conclusions: The study suggests that the mortality rate of lesser meal worm is increase with the increase of insecticide dose. The LD50 values of the insecticides are inversely related to the toxicity of the insecticides i.e. higher the LD50 value lower the toxicity of the insecticide.

  3. The impact of warming and nutrients on algae production and microcystins in seston from the iconic lake lesser Prespa, Greece

    NARCIS (Netherlands)

    Maliaka, Valentini; Faassen, Elisabeth J.; Smolders, Alfons J.P.; Lürling, Miquel

    2018-01-01

    Lake Lesser Prespa and its adjacent pond, Vromolimni in Greece, is a shallow freshwater system and a highly protected area hosting an exceptional biodiversity. The occurrence of microcystins (MCs) producing cyanobacterial blooms in these waters during recent years can be harmful to the wildlife. We

  4. Reforesting severely degraded grassland in the Lesser Himalaya of Nepal : Effects on soil hydraulic conductivity and overland flow production

    NARCIS (Netherlands)

    Ghimire, C.P.; Bonell, Mike; Bruijnzeel, L. Adrian; Coles, Neil A.; Lubczynski, M.

    2013-01-01

    [1] Severely degraded hillslopes in the Lesser Himalaya challenge local communities as a result of the frequent occurrence of overland flow and erosion during the rainy season and water shortages during the dry season. Reforestation is often perceived as an effective way of restoring predisturbance

  5. Reforesting severely degraded grassland in the Lesser Himalaya of Central Nepal: effects on soil hydraulic conductivity and overland flow production

    NARCIS (Netherlands)

    Ghimire, C.P.; Bonell, M.; Bruijnzeel, L.A.; Coles, N.A.; Lubczynski, M.W.

    2013-01-01

    Severely degraded hillslopes in the Lesser Himalaya challenge local communities as a result of the frequent occurrence of overland flow and erosion during the rainy season and water shortages during the dry season. Reforestation is often perceived as an effective way of restoring predisturbance

  6. A lesser frigatebird (Fregata ariel) in California: a first for the state and fourth for North America

    Science.gov (United States)

    Brain L Sullivan; Marshall J. Iliff; Peter L. Ralph; C. J. Ralph; Steven T. Kelling

    2007-01-01

    This paper summarizes the occurrence and identification of California's first Lesser Frigatebird (Fregata ariel), a subadult female photographed on 15 July 2007 at Lanphere Dunes near Arcata, Humboldt Country. This record is the fourth of this species for North America and the first in the eastern Pacific Ocean of the Western Hemisphere.

  7. Two cases of fatal necrosis of the lesser pelvis in patients treated with combined radiotherapy and hyperthermia for cervical carcinoma

    NARCIS (Netherlands)

    Wiggenraad, R.; Koning, C.; Westermann, C.; Jansen, C.; van der Zee, J.

    2005-01-01

    This study reports two cases of fatal necrosis of the lesser pelvis in patients with advanced cervical carcinoma, who had received combined radiotherapy and hyperthermia. The necrosis reached far from the high dose area, in one of the cases even outside the radiation portals. Both patients initially

  8. Study on the changes of properties of Myanma lesser-used timber species following gamma-irradiation

    International Nuclear Information System (INIS)

    Kaye Thwe Kywe Aye; Win Kyi; Tin Hlaing

    2001-01-01

    The proper changes of some physical properties and mechanical properties of Leza [Laderstroemra tomentofa (PREFL.)] one of Myanmar lesser-used timber species, following radiation processing with 1 Mrad gamma-radiation has been studied. It is found that some properties of Leza-timber species are significantly changed at 95 percent confidence level. (author)

  9. Environmental pollutants in endangered vs. increasing subspecies of the lesser black-backed gull on the Norwegian Coast

    International Nuclear Information System (INIS)

    Bustnes, Jan Ove; Helberg, Morten; Strann, Karl-Birger; Skaare, Janneche Utne

    2006-01-01

    Organochlorine (OC) residues were measured in eggs and blood of different subspecies of the lesser black-backed gull, Larus fuscus, on the Norwegian coast: a) increasing L. f. intermedius in the North Sea; b) endangered L. f. fuscus near the Arctic Circle; c) L. f. fuscus and greyish-mantled gulls, with a L. f. intermedius appearance, in the Barents Sea region. The dominating OCs in lesser black-backed gulls were polychlorinated biphenyls (PCB) and p,p'-dichlorodiphenyldichloroethylene (DDE). DDE and β-hexachlorocyclohexane (β-HCH) residues were higher in L. f. fuscus compared to L. f. intermedius and greyish-mantled birds in the Barents Sea region. In the latter area, blood residues of PCB and DDE in lesser black-backed gulls were as high as in great black-backed gulls, Larus marinus, while in the other regions they were lower. The higher DDE residues in endangered L. f. fuscus compared to increasing L. f. intermedius and greyish-mantled birds, which are invading northern Norway, suggest that OCs may have played a role in the population decline of L. f. fuscus, possibly in combination with nutrient stress. - DDE and β-HCH residues were higher in an endangered compared to an increasing subspecies of lesser black-backed gulls in Norway

  10. GPS tracking data of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coast

    NARCIS (Netherlands)

    Stienen, E.W.M.; Desmet, P.; Aelterman, B.; Courtens, W.; Feys, S.; Vanermen, N.; Verstraete, H.; Van de Walle, M.; Deneudt, K.; Hernandez, F.; Houthoofdt, R.; Vanhoorne, B.; Bouten, W.; Buijs, R.-J.; Kavelaars, M.M.; Müller, W.; Herman, D.; Matheve, H.; Sotillo, A.; Lens, L.

    2016-01-01

    In this data paper, Bird tracking - GPS tracking of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coast is described, a species occurrence dataset published by the Research Institute for Nature and Forest (INBO). The dataset (version 5.5) contains close to 2.5

  11. Differential gene expressions of the MAPK signaling pathway in enterovirus 71-infected rhabdomyosarcoma cells

    Directory of Open Access Journals (Sweden)

    Weifeng Shi

    Full Text Available BACKGROUND: Mitogen-activated protein kinase (MAPK signaling pathway plays an important role in response to viral infection. The aim of this study was to explore the function and mechanism of MAPK signaling pathway in enterovirus 71 (EV71 infection of human rhabdomyosarcoma (RD cells. METHODS: Apoptosis of RD cells was observed using annexin V-FITC/PI binding assay under a fluorescence microscope. Cellular RNA was extracted and transcribed to cDNA. The expressions of 56 genes of MAPK signaling pathway in EV71-infected RD cells at 8 h and 20 h after infection were analyzed by PCR array. The levels of IL-2, IL-4, IL-10, and TNF-α in the supernatant of RD cells infected with EV71 at different time points were measured by ELISA. RESULTS: The viability of RD cells decreased obviously within 48 h after EV71 infection. Compared with the control group, EV71 infection resulted in the significantly enhanced releases of IL-2, IL-4, IL-10 and TNF-α from infected RD cells (p < 0.05. At 8 h after infection, the expressions of c-Jun, c-Fos, IFN-i, MEKK1, MLK3 and NIK genes in EV71-infected RD cells were up-regulated by 2.08-6.12-fold, whereas other 19 genes (e.g. AKT1, AKT2, E2F1, IKK and NF-κB1 exhibited down-regulation. However, at 20 h after infection, those MAPK signaling molecules including MEKK1, ASK1, MLK2, MLK3, NIK, MEK1, MEK2, MEK4, MEK7, ERK1, JNK1 and JNK2 were up-regulated. In addition, the expressions of AKT2, ELK1, c-Jun, c-Fos, NF-κB p65, PI3K and STAT1 were also increased. CONCLUSION: EV71 infection induces the differential gene expressions of MAPK signaling pathway such as ERK, JNK and PI3K/AKT in RD cells, which may be associated with the secretions of inflammatory cytokines and host cell apoptosis.

  12. Dispersal, mating events and fine-scale genetic structure in the lesser flat-headed bats.

    Directory of Open Access Journals (Sweden)

    Panyu Hua

    Full Text Available Population genetic structure has important consequences in evolutionary processes and conservation genetics in animals. Fine-scale population genetic structure depends on the pattern of landscape, the permanent movement of individuals, and the dispersal of their genes during temporary mating events. The lesser flat-headed bat (Tylonycteris pachypus is a nonmigratory Asian bat species that roosts in small groups within the internodes of bamboo stems and the habitats are fragmented. Our previous parentage analyses revealed considerable extra-group mating in this species. To assess the spatial limits and sex-biased nature of gene flow in the same population, we used 20 microsatellite loci and mtDNA sequencing of the ND2 gene to quantify genetic structure among 54 groups of adult flat-headed bats, at nine localities in South China. AMOVA and F(ST estimates revealed significant genetic differentiation among localities. Alternatively, the pairwise F(ST values among roosting groups appeared to be related to the incidence of associated extra-group breeding, suggesting the impact of mating events on fine-scale genetic structure. Global spatial autocorrelation analyses showed positive genetic correlation for up to 3 km, indicating the role of fragmented habitat and the specialized social organization as a barrier in the movement of individuals among bamboo forests. The male-biased dispersal pattern resulted in weaker spatial genetic structure between localities among males than among females, and fine-scale analyses supported that relatedness levels within internodes were higher among females than among males. Finally, only females were more related to their same sex roost mates than to individuals from neighbouring roosts, suggestive of natal philopatry in females.

  13. The Lesser Antillean Iguana (Iguana delicatissima) on St. Eustatius: genetically depauperate and threatened by ongoing hybridization.

    Science.gov (United States)

    van den Burg, Matthijs P; Meirmans, Patrick G; Wagensveld, Tim van; Kluskens, Bart; Madden, Hannah; Welch, Mark E; Breeuwer, Johannes A J

    2018-02-19

    The Lesser Antillean Iguana (Iguana delicatissima) is an endangered species threatened by habitat loss and hybridization with non-native Green Iguanas (Iguana iguana). Iguanadelicatissima has been extirpated on several islands, and the Green Iguana has invaded most islands with extant populations. Information is essential to protect this species from extinction. We collected data on 293 iguanas including 17 juveniles from St. Eustasius, one of the few remaining I. delicatissima strongholds. Genetic data was leveraged to test for hybridization presence with the Green Iguana using both mitochondrial and nuclear genes, including 16 microsatellite loci. The microsatellites were also analysed to estimate genetic diversity, population structure and effective population size. Using molecular and morphological data we identified 286 I. delicatissima individuals captured during our first fieldwork effort, and seven non-native iguanas captured during a second effort, showing hybridization occurs within this population. Comparing homologous microsatellites used in studies on Dominica and Chancel, the I. delicatissima population on St. Eustatius has extremely low genetic diversity (HO=0.051; HE=0.057), suggesting this population is genetically depauperate. Furthermore, there is significant evidence for inbreeding (FIS=0.12) and weak spatial genetic structure (FST=0.021, p=0.002) within this population. Besides immediate threats including hybridization, this population's low genetic diversity, presence of physiological abnormalities and low recruitment could indicate presence of inbreeding depression that threatens its long-term survival. We conclude there is a continued region-wide threat to I. delicatissima and highlight the need for immediate conservation action to stop the continuing spread of Green Iguanas and to eliminate hybridization from St. Eustatius.

  14. Combining multiple sources of data to inform conservation of Lesser Prairie-Chicken populations

    Science.gov (United States)

    Ross, Beth; Haukos, David A.; Hagen, Christian A.; Pitman, James

    2018-01-01

    Conservation of small populations is often based on limited data from spatially and temporally restricted studies, resulting in management actions based on an incomplete assessment of the population drivers. If fluctuations in abundance are related to changes in weather, proper management is especially important, because extreme weather events could disproportionately affect population abundance. Conservation assessments, especially for vulnerable populations, are aided by a knowledge of how extreme events influence population status and trends. Although important for conservation efforts, data may be limited for small or vulnerable populations. Integrated population models maximize information from various sources of data to yield population estimates that fully incorporate uncertainty from multiple data sources while allowing for the explicit incorporation of environmental covariates of interest. Our goal was to assess the relative influence of population drivers for the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) in the core of its range, western and southern Kansas, USA. We used data from roadside lek count surveys, nest monitoring surveys, and survival data from telemetry monitoring combined with climate (Palmer drought severity index) data in an integrated population model. Our results indicate that variability in population growth rate was most influenced by variability in juvenile survival. The Palmer drought severity index had no measurable direct effects on adult survival or mean number of offspring per female; however, there were declines in population growth rate following severe drought. Because declines in population growth rate occurred at a broad spatial scale, declines in response to drought were likely due to decreases in chick and juvenile survival rather than emigration outside of the study area. Overall, our model highlights the importance of accounting for environmental and demographic sources of variability, and provides a thorough

  15. Combining Geological and Geophysical Data in Volcanic Hazard Estimation for Dominica, Lesser Antilles

    Science.gov (United States)

    George, O.; Latchman, J. L.; Connor, C.; Malservisi, R.; Connor, L.

    2014-12-01

    Risk posed by volcanic eruptions are generally quantified in a few ways; in the short term geophysical data such as seismic activity or ground deformation are used to assess the state of volcanic unrest while statistical approaches such as spatial density estimates are used for long term hazard assessment. Spatial density estimates have been used in a number of monogenetic volcanic fields for hazard map generation and utilize the age, location and volumes of previous eruptions to calculate the probability of a new event occurring at a given location within this field. In a previously unpublished study, spatial density estimates of the Lesser Antilles volcanic arc showed the island of Dominica to have the highest likelihood of future vent formation. In this current study, this technique was used in combination with relocated seismic events occurring beneath Dominica within the last ~ 20 years as well as InSAR images of ground deformation to generate a hazard map which not only takes into consideration the past events but also the current state of unrest. Here, geophysical data serve as a weighting factor in the estimates with those centers showing more vigorous activity receiving stronger favorability in the assessment for future activity. In addition to this weighting, the bandwidth utilized in the 2D-radially symmetric kernel density function was optimized using the SAMSE method so as to find the value which best minimizes the error in the estimate. The end results of this study are dynamic volcanic hazards maps which will be readily updatable as changes in volcanic unrest occurs within the system.

  16. Dispersal, mating events and fine-scale genetic structure in the lesser flat-headed bats.

    Science.gov (United States)

    Hua, Panyu; Zhang, Libiao; Guo, Tingting; Flanders, Jon; Zhang, Shuyi

    2013-01-01

    Population genetic structure has important consequences in evolutionary processes and conservation genetics in animals. Fine-scale population genetic structure depends on the pattern of landscape, the permanent movement of individuals, and the dispersal of their genes during temporary mating events. The lesser flat-headed bat (Tylonycteris pachypus) is a nonmigratory Asian bat species that roosts in small groups within the internodes of bamboo stems and the habitats are fragmented. Our previous parentage analyses revealed considerable extra-group mating in this species. To assess the spatial limits and sex-biased nature of gene flow in the same population, we used 20 microsatellite loci and mtDNA sequencing of the ND2 gene to quantify genetic structure among 54 groups of adult flat-headed bats, at nine localities in South China. AMOVA and F(ST) estimates revealed significant genetic differentiation among localities. Alternatively, the pairwise F(ST) values among roosting groups appeared to be related to the incidence of associated extra-group breeding, suggesting the impact of mating events on fine-scale genetic structure. Global spatial autocorrelation analyses showed positive genetic correlation for up to 3 km, indicating the role of fragmented habitat and the specialized social organization as a barrier in the movement of individuals among bamboo forests. The male-biased dispersal pattern resulted in weaker spatial genetic structure between localities among males than among females, and fine-scale analyses supported that relatedness levels within internodes were higher among females than among males. Finally, only females were more related to their same sex roost mates than to individuals from neighbouring roosts, suggestive of natal philopatry in females.

  17. VoiLA: A multidisciplinary study of Volatile recycling in the Lesser Antilles Arc

    Science.gov (United States)

    Collier, J.; Blundy, J. D.; Goes, S. D. B.; Henstock, T.; Harmon, N.; Kendall, J. M.; Macpherson, C.; Rietbrock, A.; Rychert, C.; Van Hunen, J.; Wilkinson, J.; Wilson, M.

    2017-12-01

    Project VoiLA will address the role of volatiles in controlling geological processes at subduction zones. The study area was chosen as it subducts oceanic lithosphere formed at the slow-spreading Mid Atlantic Ridge. This should result in a different level and pattern of hydration to compare with subduction zones in the Pacific which consume oceanic lithosphere generated at faster spreading rates. In five project components, we will test (1) where volatiles are held within the incoming plate; (2) where they are transported and released below the arc; (3) how the volatile distribution and pathways relate to the construction of the arc; and (4) their relationship to seismic and volcanic hazards and the fractionation of economic metals. Finally, (5) the behaviour of the Lesser Antilles arc will be compared with that of other well-studied systems to improve our wider understanding of the role of water in subduction processes. To address these questions the project will combine seismology; petrology and numerical modelling of wedge dynamics and its consequences on dehydration and melting. So-far island-based fieldwork has included mantle xenolith collection and installation of a temporary seismometer network. In 2016 and 2017 we conducted cruises onboard the RRS James Cook that collected a network of passive-recording and active-recording ocean-bottom seismometer data within the back-arc, fore-arc and incoming plate region. A total of 175 deployments and recoveries were made with the loss of only 6 stations. The presentation will present preliminary results from the project.

  18. Assessment of lesser prairie-chicken lek density relative to landscape characteristics in Texas

    Energy Technology Data Exchange (ETDEWEB)

    Timmer, Jennifer; Butler, Matthew; Ballard, Warren; Boal, Clint; Whitlaw, Heather

    2012-08-31

    My 2.5-yr Master's project accomplished the objectives of estimating lesser prairie-chicken (LPC) lek density and abundance in the Texas occupied range and modeling anthropogenic and landscape features associated with lek density by flying helicopter lek surveys for 2 field seasons and employing a line-transect distance sampling method. This project was important for several reasons. Firstly, wildlife managers and biologists have traditionally monitored LPC populations with road-based surveys that may result in biased estimates and do not provide access to privately-owned or remote property. From my aerial surveys and distance sampling, I was able to provide accurate density and abundance estimates, as well as new leks and I detected LPCs outside the occupied range. Secondly, recent research has indicated that energy development has the potential to impact LPCs through avoidance of tall structures, increased mortality from raptors perching on transmission lines, disturbance to nesting hens, and habitat loss/fragmentation. Given the potential wind energy development in the Texas Panhandle, spatial models of current anthropogenic and vegetative features (such as transmission lines, roads, and percent native grassland) influencing lek density were needed. This information provided wildlife managers and wind energy developers in Texas with guidelines for how change in landscape features could impact LPCs. Lastly, LPC populations have faced range-wide declines over the last century and they are currently listed as a candidate species under the Endangered Species Act. I was able to provide timely information on LPC populations in Texas that will be used during the listing process.

  19. GIS habitat analysis for lesser prairie-chickens in southeastern New Mexico

    Directory of Open Access Journals (Sweden)

    Neville Paul

    2006-12-01

    Full Text Available Abstract Background We conducted Geographic Information System (GIS habitat analyses for lesser prairie-chicken (LPCH, Tympanuchus pallidicinctus conservation planning. The 876,799 ha study area included most of the occupied habitat for the LPCH in New Mexico. The objectives were to identify and quantify: 1. suitable LPCH habitat in New Mexico, 2. conversion of native habitats, 3. potential for habitat restoration, and 4. unsuitable habitat available for oil and gas activities. Results We found 16% of suitable habitat (6% of the study area distributed in 13 patches of at least 3,200 ha and 11% of suitable habitat (4% of the study area distributed in four patches over 7,238 ha. The area converted from native vegetation types comprised 17% of the study area. Ninety-five percent of agricultural conversion occurred on private lands in the northeastern corner of the study area. Most known herbicide-related conversions (82% occurred in rangelands in the western part of the study area, on lands managed primarily by the US Bureau of Land Management (BLM. We identified 88,190 ha (10% of the study area of habitats with reasonable restoration potential. Sixty-two percent of the primary population area (PPA contained occupied, suitable, or potentially suitable habitat, leaving 38% that could be considered for oil and gas development. Conclusion Although suitable LPCH habitat appears at first glance to be abundant in southeastern New Mexico, only a fraction of apparently suitable vegetation types constitute quality habitat. However, we identified habitat patches that could be restored through mesquite control or shin-oak reintroduction. The analysis also identified areas of unsuitable habitat with low restoration potential that could be targeted for oil and gas exploration, in lieu of occupied, high-quality habitats. Used in combination with GIS analysis and current LPCH population data, the habitat map represents a powerful conservation and management tool.

  20. GIS habitat analysis for lesser prairie-chickens in southeastern New Mexico.

    Science.gov (United States)

    Johnson, Kristine; Neville, Teri B; Neville, Paul

    2006-12-04

    We conducted Geographic Information System (GIS) habitat analyses for lesser prairie-chicken (LPCH, Tympanuchus pallidicinctus) conservation planning. The 876,799 ha study area included most of the occupied habitat for the LPCH in New Mexico. The objectives were to identify and quantify: 1. suitable LPCH habitat in New Mexico, 2. conversion of native habitats, 3. potential for habitat restoration, and 4. unsuitable habitat available for oil and gas activities. We found 16% of suitable habitat (6% of the study area) distributed in 13 patches of at least 3,200 ha and 11% of suitable habitat (4% of the study area) distributed in four patches over 7,238 ha. The area converted from native vegetation types comprised 17% of the study area. Ninety-five percent of agricultural conversion occurred on private lands in the northeastern corner of the study area. Most known herbicide-related conversions (82%) occurred in rangelands in the western part of the study area, on lands managed primarily by the US Bureau of Land Management (BLM). We identified 88,190 ha (10% of the study area) of habitats with reasonable restoration potential. Sixty-two percent of the primary population area (PPA) contained occupied, suitable, or potentially suitable habitat, leaving 38% that could be considered for oil and gas development. Although suitable LPCH habitat appears at first glance to be abundant in southeastern New Mexico, only a fraction of apparently suitable vegetation types constitute quality habitat. However, we identified habitat patches that could be restored through mesquite control or shin-oak reintroduction. The analysis also identified areas of unsuitable habitat with low restoration potential that could be targeted for oil and gas exploration, in lieu of occupied, high-quality habitats. Used in combination with GIS analysis and current LPCH population data, the habitat map represents a powerful conservation and management tool.

  1. Relocalizing a historical earthquake using recent methods: The 10 November 1935 Earthquake near Montserrat, Lesser Antilles

    Science.gov (United States)

    Niemz, P.; Amorèse, D.

    2016-03-01

    This study investigates the hypothesis of Feuillet et al. (2011) that the hypocenter of the seismic event on November 10, 1935 near Montserrat, Lesser Antilles (MS 6 1/4) (Gutenberg and Richter, 1954) was mislocated by other authors and is actually located in the Montserrat-Havers fault zone. While this proposal was based both on a Ground Motion Prediction Equation and on the assumption that earthquakes in this region are bound to prominent fault systems, our study relies on earthquake localization methods using arrival times of the International Seismological Summary (ISS). Results of our methodology suggest that the hypocenter was really located at 16.90° N, 62.53° W. This solution is about 25 km north-west of the location proposed by Feuillet et al. (2011) within the Redonda fault system, northward of the Montserrat-Havers fault zone. As depth phases that contribute valuable insights to the focal depth are not included in the ISS data set and the reassociation of these phases is difficult, the error in depth is high. Taking into account tectonic constraints and the vertical extend of NonLinLoc's uncertainty area of the preferred solution we assume that the focus is most probably in the lower crust between 20 km and the Moho. Our approach shows that the information of the ISS can lead to a reliable solution even without an exhaustive search for seismograms and station bulletins. This is encouraging for a better assessment of seismic and tsunami hazard in the Caribbean, Mexico, South and Central America, where many moderate to large earthquakes occurred in the first half of the 20th century. The limitations during this early phase of seismology which complicate such relocations are described in detail in this study.

  2. Do Zircon age Spectra Record Magmatic Cyclicity at Soufrière (Saint Lucia, Lesser Antilles)?

    Science.gov (United States)

    Schmitt, A. K.; Stockli, D. F.; Lindsay, J. M.

    2007-12-01

    The Soufrière Volcanic Center (Saint Lucia, Lesser Antilles) is a long-lived arc-volcanic system that evolved over the past 5 - 6 Ma. Its most recent volcanic activity between 20 and 40 ka was concentrated within the prominent Qualibou topographic depression and produced two voluminous pyroclastic deposits: Choiseul and the overlying Belfond. In addition, several dacitic lava domes exist within the Qualibou depression. Because evidence of earlier volcanic activity in long-lived magma systems is frequently obliterated by subsequent eruptive or volcano-tectonic events, high spatial resolution U-Th dating of zircon combined with (U-Th)/He dating is a powerful tool to identify magma crystallization episodes at depth and to link these to the eruptive record. U-Th model ages and disequilibrium corrected U-Pb ages for 56 individual zircons from Soufrière lavas (Morne Bonin, Belfond, Terre Blanche) and pumice (Choiseul, Belfond) were determined by secondary ionization mass spectrometry. The majority of results is on unpolished zircons where analysis pits integrate over the outermost ~10 μm of individual grains with a lateral spatial resolution of ~40 μm. Selected grains were subsequently analyzed by (U-Th)/He methods. Belfond and Terre Blanche (U-Th)/He zircon ages (~20 ka) agree with previous 14C charcoal ages, whereas Morne Bonin ages are much older (~250 ka). Overall, the U-Th zircon crystallization age spectrum reveals a remarkable range between ~20 and ~600 ka and displays multiple peaks, among which the most prominent are tentatively identified at ~40 ka, ~80 ka, ~130 ka, ~200 ka and ~500 ka. The distribution of rim ages indicates that most zircons lack overgrowth dating from just prior to the eruption, but the youngest ages for each sample overlap with the eruption ages. Soufrière zircons thus reveal magma intrusion, cooling, and crystallization cycles within the underlying plutonic system for which the volcanic stratigraphic record is sketchy.

  3. The parasitic eyeworm Oxyspirura petrowi as a possible cause of decline in the threatened lesser prairie-chicken (Tympanuchus pallidicinctus.

    Directory of Open Access Journals (Sweden)

    Nicholas R Dunham

    Full Text Available Lesser prairie-chickens (Tympanuchus pallidicinctus have been declining range wide since the early 1900's despite efforts to establish conservation and improve their habitat. In early 2014, the lesser prairie-chicken was listed as a threatened species under the U.S Endangered Species Act and the need to find out why they are declining is more important than ever. Nine hunter shot lesser prairie-chickens were donated and sampled for the presence or absence of the eyeworm Oxyspirura petrowi, a known parasite that can cause damage to the eye of its host, and common environmental contaminants. Eyeworm infection was found in 7 of 9 birds (78% infection rate with an infection range between 0-16 O. petrowi per bird. Breast, liver, and fat tissue samples from the lesser prairie-chickens were analyzed for the frequency of 20 organochlorine pesticides. Femurs and livers were also tested on these birds for metal contaminants. Pesticides were found in several samples above the detection limits but were still in the low ng/g range. Notable was the ubiquitous presence of endrin aldehyde across all tissues. One femur showed 5.66 µg/g of lead (Pb but this is still relatively low. No liver samples had elevated mercury (Hg above detection limits. The presence of these organochlorines is consistent with the historic use of pesticides in this region. With pesticide and metals found in such low levels and parasitic nematode infections at rather high levels, it is recommended that these parasites be further evaluated as a contributing factor to the decline of the lesser prairie-chicken.

  4. Nesting ecology and nest survival of lesser prairie-chickens on the Southern High Plains of Texas

    Science.gov (United States)

    Grisham, Blake A.; Borsdorf, Philip K.; Boal, Clint W.; Boydston, Kathy K.

    2014-01-01

    The decline in population and range of lesser prairie-chickens (Tympanuchus pallidicinctus) throughout the central and southern Great Plains has raised concerns considering their candidate status under the United States Endangered Species Act. Baseline ecological data for lesser prairie-chickens are limited, especially for the shinnery oak-grassland communities of Texas. This information is imperative because lesser prairie-chickens in shinnery oak grasslands occur at the extreme southwestern edge of their distribution. This geographic region is characterized by hot, arid climates, less fragmentation, and less anthropogenic development than within the remaining core distribution of the species. Thus, large expanses of open rangeland with less anthropogenic development and a climate that is classified as extreme for ground nesting birds may subsequently influence nest ecology, nest survival, and nest site selection differently compared to the rest of the distribution of the species. We investigated the nesting ecology of 50 radio-tagged lesser prairie-chicken hens from 2008 to 2011 in the shinnery oak-grassland communities in west Texas and found a substantial amount of inter-annual variation in incubation start date and percent of females incubating nests. Prairie-chickens were less likely to nest near unimproved roads and utility poles and in areas with more bare ground and litter. In contrast, hens selected areas dominated by grasses and shrubs and close to stock tanks to nest. Candidate models including visual obstruction best explained daily nest survival; a 5% increase in visual obstruction improved nest survival probability by 10%. The model-averaged probability of a nest surviving the incubation period was 0.43 (SE = 0.006; 95% CI: 0.23, 0.56). Our findings indicate that lesser prairie-chicken reproduction during our study period was dynamic and was correlated with seasonal weather patterns that ultimately promoted greater grass growth earlier in the

  5. Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

    Science.gov (United States)

    Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

    2017-06-01

    Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Removing cosmic rays and other randomly positioned spurious events from CCD images by taking the lesser image -statistical theory for the general case

    International Nuclear Information System (INIS)

    Kay, L.

    1992-01-01

    If two optical images of the same scene are obtained using a charged-coupled device (CCD), a third image (called the lesser image) may be formed in computer memory by taking the lesser of the two counts in each pixel. The process may be used to remove, or greatly reduce, the effect of spurious events such as cosmic rays. A complete statistical theory of the lesser image is given for the general case, thereby facilitating recovery of the true image from the lesser image. (author)

  7. The ER stress-mediated mitochondrial apoptotic pathway and MAPKs modulate tachypacing-induced apoptosis in HL-1 atrial myocytes.

    Directory of Open Access Journals (Sweden)

    Jiaojiao Shi

    Full Text Available Cell apoptosis is a contributing factor in the initiation, progression and relapse of atrial fibrillation (AF, a life-threatening illness accompanied with stroke and heart failure. However, the regulatory cascade of apoptosis is intricate and remains unidentified, especially in the setting of AF. The aim of this study was to explore the roles of endoplasmic reticulum (ER stress, mitochondrial apoptotic pathway (MAP, mitogen-activated protein kinases (MAPKs, and their cross-talking in tachypacing-induced apoptosis.HL-1 cells were cultured in the presence of tachypacing for 24 h to simulate atrial tachycardia remodeling. Results showed that tachypacing reduced cell viability measured by the cell counting kit-8, dissipated mitochondrial membrane potential detected by JC-1 staining and resulted in approximately 50% apoptosis examined by Hoechst staining and annexin V/propidium iodide staining. In addition, the proteins involved in ER stress, MAP and MAPKs were universally up-regulated or activated via phosphorylation, as confirmed by western blotting; and reversely silencing of ER stress, caspase-3 (the ultimate executor of MAP and MAPKs with specific inhibitors prior to pacing partially alleviated apoptosis. An inhibitor of ER stress was applied to further investigate the responses of mitochondria and MAPKs to ER stress, and results indicated that suppression of ER stress comprehensively but incompletely attenuated the activation of MAP and MAPKs aroused by tachypacing, with the exception of ERK1/2, one branch of MAPKs.Our study suggested tachypacing-induced apoptosis is regulated by ER stress-mediated MAP and MAPKs. Thus, the above three components are all promising anti-apoptotic targets in AF patients and ER stress appears to play a dominant role due to its comprehensive effects.

  8. Involvement of Mos-MEK-MAPK pathway in cytostatic factor (CSF) arrest in eggs of the parthenogenetic insect, Athalia rosae.

    Science.gov (United States)

    Yamamoto, Daisuke S; Tachibana, Kazunori; Sumitani, Megumi; Lee, Jae Min; Hatakeyama, Masatsugu

    2008-01-01

    Extensive survey of meiotic metaphase II arrest during oocyte maturation in vertebrates revealed that the mitogen-activated protein kinase (MAPK) pathway regulated by the c-mos proto-oncogene product, Mos, has an essential role in cytostatic activity, termed cytostatic factor (CSF). In contrast, little is known in invertebrates in which meiotic arrest occurs in most cases at metaphase I (MI arrest). A parthenogenetic insect, the sawfly Athalia rosae, in which artificial egg activation is practicable, has advantages to investigate the mechanisms of MI arrest. Both the MAPK/extracellular signal-regulated protein kinase kinase (MEK) and MAPK were phosphorylated and maintained active in MI-arrested sawfly eggs, whereas they were dephosphorylated soon after egg activation. Treatment of MI-arrested eggs with U0126, an inhibitor of MEK, resulted in dephosphorylation of MAPK and MI arrest was resumed. The sawfly c-mos gene orthologue encoding a serine/threonine kinase was cloned and analyzed. It was expressed in nurse cells in the ovaries. To examine CSF activity of the sawfly Mos, synthesized glutathione S-transferase (GST)-fusion sawfly Mos protein was injected into MI-resumed eggs in which MEK and MAPK were dephosphorylated. Both MEK and MAPK were phosphorylated again upon injection. In these GST-fusion sawfly Mos-injected eggs subsequent mitotic (syncytial) divisions were blocked and embryonic development was ceased. These results demonstrated that the MEK-MAPK pathway was involved in maintaining CSF arrest in sawfly eggs and Mos functioned as its upstream regulatory molecule.

  9. Electroacupuncture Inhibits the Activation of p38MAPK in the Central Descending Facilitatory Pathway in Rats with Inflammatory Pain

    Directory of Open Access Journals (Sweden)

    Man-Li Hu

    2017-01-01

    Full Text Available The mitogen-activated protein kinases (MAPKs, especially p38MAPK, play a pivotal role in chronic pain. Electroacupuncture (EA relieves inflammatory pain underlying the descending pathway, that is, the periaqueductal gray (PAG, the rostral ventromedial medulla (RVM, and the spinal cord dorsal horn (SCDH. However, whether EA antagonizes inflammatory pain through regulation of p38MAPK in this descending facilitatory pathway is unclear. Complete Freund’s adjuvant (CFA was injected into the hind paw of rats to establish inflammatory pain model. EA was administrated for 30 min at Zusanli and Kunlun acupoints at 0.5, 24.5, 48.5, and 72.5 h, respectively. The paw withdrawal threshold (PWT, paw edema, and Phosphor-p38MAPK-Immunoreactivity (p-p38MAPK-IR cells were measured before (0 h and at 1, 3, 5, 7, 25, and 73 h after CFA or saline injection. EA increased PWT at 1, 3, 25, and 73 h and inhibited paw edema at 25 and 73 h after CFA injection. Moreover, the increasing number of p-p38MAPK-IR cells which was induced by CFA was suppressed by EA stimulation in PAG and RVM at 3 and 5 h and in SCDH at 5, 7, 25, and 73 h. These results suggest that EA suppresses inflammation-induced hyperalgesia probably through inhibiting p38MAPK activation in the descending facilitatory pathway.

  10. MAPK phosphatase AP2C3 induces ectopic proliferation of epidermal cells leading to stomata development in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Julija Umbrasaite

    2010-12-01

    Full Text Available In plant post-embryonic epidermis mitogen-activated protein kinase (MAPK signaling promotes differentiation of pavement cells and inhibits initiation of stomata. Stomata are cells specialized to modulate gas exchange and water loss. Arabidopsis MAPKs MPK3 and MPK6 are at the core of the signaling cascade; however, it is not well understood how the activity of these pleiotropic MAPKs is constrained spatially so that pavement cell differentiation is promoted only outside the stomata lineage. Here we identified a PP2C-type phosphatase termed AP2C3 (Arabidopsis protein phosphatase 2C that is expressed distinctively during stomata development as well as interacts and inactivates MPK3, MPK4 and MPK6. AP2C3 co-localizes with MAPKs within the nucleus and this localization depends on its N-terminal extension. We show that other closely related phosphatases AP2C2 and AP2C4 are also MAPK phosphatases acting on MPK6, but have a distinct expression pattern from AP2C3. In accordance with this, only AP2C3 ectopic expression is able to stimulate cell proliferation leading to excess stomata development. This function of AP2C3 relies on the domains required for MAPK docking and intracellular localization. Concomitantly, the constitutive and inducible AP2C3 expression deregulates E2F-RB pathway, promotes the abundance and activity of CDKA, as well as changes of CDKB1;1 forms. We suggest that AP2C3 downregulates the MAPK signaling activity to help maintain the balance between differentiation of stomata and pavement cells.

  11. Oral administration of Lentinus edodes β-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARγ pathways.

    Science.gov (United States)

    Shi, Limin; Lin, Qinlu; Yang, Tao; Nie, Ying; Li, Xinhua; Liu, Bo; Shen, Junjun; Liang, Ying; Tang, Yiping; Luo, Feijun

    2016-11-09

    To evaluate the anti-inflammatory effect of β-glucans from Lentinus edodes, and its molecular mechanism, the dextran sulfate sodium salt (DSS) induced colitis model of mice and the LPS-stimulated RAW264.7 cell inflammation model were used in this study. 40 ICR male mice were randomly divided into 4 groups: Control, DSS (DSS treated only), DSS + low-βGs (500 mg kg -1 d -1 ) and DSS + high-βGs (1000 mg kg -1 d -1 ). The body weight of the mice with Lentinus edodes β-glucan supplementation increased significantly compared to the DSS group and the disease activity index (DAI) was improved in both βG-treated groups. Compared with the DSS group, histopathological analysis showed that the infiltration of inflammatory cells of both βG-treated groups decreased significantly in colonic tissues. Furthermore, oral administration of β-glucans decreases the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) and inhibits the expression of iNOS and several inflammatory factors: TNF-α, IL-1β and IL-6 as well as nitric oxide (NO) of the colonic tissues. The mitogen-activated protein kinase (MAPK) pathway is closely related to the expression of pro-inflammatory factors. In the DSS-induced colitis model and the LPS-stimulated RAW264.7 cell model, βGs inhibited the expression of pro-inflammatory factors and blocked the phosphorylation of JNK/ERK1/2 and p38; βGs also suppress the phosphorylation of Elk-1 at Ser84 and the phosphorylation of PPARγ at Ser112. Altogether, these results suggest that Lentinus edodes βGs could inhibit the DSS-induced ulcerative colitis and decrease inflammatory factor expressions. The molecular mechanism may be involved in suppressing MAPK signaling and inactivation of Elk-1 and activation of PPARγ.

  12. Lithic assemblages of Azokh Cave (Nagorno Karabagh, Lesser Caucasus: Raw materials, technology and regional context

    Directory of Open Access Journals (Sweden)

    Lena Asryan

    2014-03-01

    Full Text Available Azokh Cave is a Middle Pleistocene to Holocene site located in Nagorno Karabagh (Lesser Caucasus. The main entrance, Azokh 1, is a large cave that has two geological sequences (lower and upper with nine geo-archaeological units of which only the upper ones (Units I to V have a significant archaeological record.  The faunal remains and lithic artefacts in these units indicate aspects of human occupation, and exploitation of, and association with animals.     The lithic artefacts presented here were recovered from Units V, III and II during the 2002 – 2009 excavation seasons. The available chronological data indicates an age between 293 – 100 Ka for these units. The operational chain is incomplete and artefacts found in the cave are primarily end-products dominated by flake-tools. The assemblage of Unit V is composed primarily of simple, unretouched flakes with a minimal presence of retouched flakes and cores. The Unit II lithic assemblage includes a substantial Levallois component, although with fewer cores and retouched flakes. There are very few flake tools in Unit III. While it is still difficult to assign the Unit V assemblage to a techno-typological group or complex (i.e. Acheulean, Mousterian or other local techno-complexes such as the Kudarian, the Unit II assemblage is clearly associated with Mode 3 or the Mousterian techno-complex.Different local and non-local raw materials were exploited in all units for the production of lithic artefacts, although the range of raw materials is more varied in Unit II. Local chert, flint and basalt were used most commonly, probably due to their easy accessibility. Limestone, jasper and sandstone, from local and non-local sources, are present in small quantities in Units V and II. Obsidian is the only raw material that possibly originates from more distant sources. Flint and chert appear to have been preferentially exploited for flake tool production in all units, but the toolmakers show a

  13. Botanical ethnoveterinary therapies in three districts of the Lesser Himalayas of Pakistan.

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    Abbasi, Arshad Mehmood; Khan, Shujaul Mulk; Ahmad, Mushtaq; Khan, Mir Ajab; Quave, Cassandra Leah; Pieroni, Andrea

    2013-12-20

    Ethnoveterinary knowledge is highly significant for persistence of traditional community-based approaches to veterinary care. This is of particular importance in the context of developing and emerging countries, where animal health (that of livestock, especially) is crucial to local economies and food security. The current survey documents the traditional veterinary uses of medicinal plants in the Lesser Himalayas-Pakistan. Data were collected through interviews, focus groups, participant observation, and by administering questionnaires. A total of 105 informants aged between 20-75 years old who were familiar with livestock health issues (i.e. farmers, shepherds, housewives and herbalists) participated in the study. A total of 89 botanical taxa, belonging to 46 families, were reported to have ethnoveterinary applications. The most quoted families were Poaceae (6 taxa), Fabaceae (6), Asteraceae (5), and Polygonaceae (5). Adhatoda vasica was the most cited species (43%), followed by Trachyspermum ammi (37%), and Zanthoxylum armatum var. armatum (36%). About 126 medications were recorded against more than 50 veterinary conditions grouped into seven categories. The highest cultural index values were recorded for Trachyspermum ammi, Curcuma longa, Melia azedarach, Zanthoxylum armatum var. armatum and Adhatoda vasica. The highest informant consensus factor was found for pathologies related to respiratory and reproductive disorders. Comparison with the local plant-based remedies used in human folk medicine revealed that many of remedies were used in similar ways in local human phytotherapy. Comparison with other field surveys conducted in surrounding areas demonstrated that approximately one-half of the recorded plants uses are novel to the ethnoveterinary literature of the Himalayas. The current survey shows a remarkable resilience of ethnoveterinary botanical knowledge in the study area. Most of the species reported for ethnoveterinary applications are wild and under

  14. Mercury concentration, speciation and budget in volcanic aquifers: Italy and Guadeloupe (Lesser Antilles)

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    Bagnato, E.; Aiuppa, A.; Parello, F.; D'Alessandro, W.; Allard, P.; Calabrese, S.

    2009-01-01

    Quantifying the contribution of volcanism to global mercury (Hg) emissions is important to understand the pathways and the mechanisms of Hg cycling through the Earth's geochemical reservoirs and to assess its environmental impacts. While previous studies have suggested that degassing volcanoes might contribute importantly to the atmospheric budget of mercury, little is known about the amount and behaviour of Hg in volcanic aquifers. Here we report on detailed investigations of both the content and the speciation of mercury in aquifers of active volcanoes in Italy and Guadeloupe Island (Lesser Antilles). In the studied groundwaters, total Hg (THg) concentrations range from 10 to 500 ng/l and are lower than the 1000 ng/l threshold value for human health protection fixed by the World Health Organization [WHO (1993): WHO Guidelines for Drinking Water Quality- http://www.who.int/water_sanitation_health/GDWQ/index.htlm]. Positive co-variations of (THg) with sulphate indicate that Hg-SO 4-rich acid groundwaters receive a direct input of magmatic/hydrothermal gases carrying mercury as Hg 0(gas). Increasing THg in a volcanic aquifer could thus be a sensitive tracer of magmatic gas input prior to an eruption. Since the complex behaviour and toxicity of mercury in waters depend on its chemical speciation, we carefully determined the different aqueous forms of this element in our samples. We find that dissolved elemental Hg 0(aq) and particulate-bound Hg (Hg P) widely prevail in volcanic aquifers, in proportions that highlight the efficiency of Hg adsorption onto colloidal particles. Moreover, we observe that dissolved Hg 0aq and Hg(II) forms coexist in comparable amount in most of the waters, in stark contrast to the results of thermodynamic equilibrium modelling. Therefore, chemical equilibrium between dissolved mercury species in volcanic waters is either prevented by natural kinetic effects or not preserved in collected waters due to sampling/storage artefacts. Finally, we

  15. Stratigraphic, Granulometric and Geochemical Studies of a Major Plinian Eruption on Dominica, Lesser Antilles

    Science.gov (United States)

    Smith, A. L.; Daly, G.; Killingsworth, N.; Deuerling, K.; Schneider, S.; Fryxell, J. E.

    2008-12-01

    The island of Dominica, located in the center of the Lesser Antilles island arc has witnessed, probably within the last 100,000 years, three large volume Plinian eruptions. One of these, associated with the Morne Diablotins center, forms the Grande Savane pyroclastic flow fan, that extends off shore as a distinctive submarine feature for a distance of at least 14 km. Stratigraphical studies of road cuts and well-exposed sea cliffs indicate the fan is composed of an older unit composed of reworked deposits at the base followed by at least four sequences, based on the presence of paleosols, of block and ash flow deposits. The upper unit of block and ash flows is overlain, with no evidence of an intervening paleosol, by a sequence of ignimbrites and pumiceous surges (representing the Plinian eruption). There is no evidence of an initial Plinian fall deposit, so the lowest bed in the succession is an ignimbrite with a highly irregular base that cuts into the underlying block and ash flow deposits, the upper parts of which are colored red due to thermal effects. This lowest ignimbrite is welded (minimum porosity of 15%) throughout its thickness (maximum thickness of greater than 21 m), although a few outcrops near the margins show a thin (20-30 cm) non-welded but lithified zone beneath the welded zone. The remainder of the sequence is composed of lithified ignimbrite that can be subdivided into three units separated by pumiceous surge layers. The ignimbrite succession is overlain, with no obvious break, by a thin fall deposit containing accretionary lapilli and gas cavities, followed by three pumiceous surge deposits (lower and upper show planar stratification and the middle surge shows massive bedding); towards the north the upper two surge deposits are separated by thin pumiceous lapilli fall and ash fall deposits. This surge sequence extends laterally outside of the main area of ignimbrite deposition. The pumice clasts from the ignimbrites are andesitic in

  16. Stratigraphy and Petrology of the Grande Soufriere Hills Volcano, Dominica, Lesser Antilles

    Science.gov (United States)

    Daly, G.; Smith, A. L.; Garcia, R.; Killingsworth, N.

    2007-12-01

    The Grande Soufriere Hills volcanic center is located on the south east coast of the island of Dominica in the Lesser Antilles. Although the volcano is deeply dissected, a distinct circular crater that opens to the east can be observed. Within the crater is a lava dome and unconsolidated pyroclastic deposits mantle the southeast flanks of the volcano. These pyroclastic deposits are almost entirely matrix-supported block and ash flows and surges suggesting that Pelean-style eruptions have dominated its most recent activity. Within this sequence is a relatively thin (30-50 cm) clast-supported deposit that has been interpreted as a possible blast deposit. Two age dates from these younger deposits suggest that much of this activity occurred between l0,000 and 12,000 years ago. On the southeastern coast at Pointe Mulâtre and extending approximately 4 km north and at a maximum 2 km west, is a megabreccia of large (up to 3 m) flow-banded andesite clasts set in a semi-lithified medium grained ash matrix. At Pointe Mulâtre this megabreccia is overlain by unconsolidated block and ash flow deposits. To the north of the megabreccia, exposures in the sea cliffs reveal a consolidated sequence of well-bedded alternating coarse and fine deposits suggesting deltaic foreset beds; which in turn appears to be overlain by a yellow- colored relatively coarse flow deposit with an irregular upper surface. The uppermost deposits in the sea cliffs are a sequence of unconsolidated block and ash flow deposits and interbedded fluviatile conglomerates equivalent to the younger flow deposits logged inland. Volcanic rocks from the Grande Soufriere Hills are all porphyritic andesites often containing hypabyssal inclusions. Dominant phenocrysts are plagioclase often with inclusion-rich cores and well developed zoning. Mafic phenocrysts include hornblende, augite and hypersthene. Geochemically these andesites range from 58- 63% SiO2 and show trends of decreasing values for Al2O3, FeO, MgO, CaO, Ti

  17. A Multi-analytical Approach for the Characterization of Marbles from Lesser Himalayas (Northwest Pakistan)

    Science.gov (United States)

    Fahad, M.; Iqbal, Y.; Riaz, M.; Ubic, R.; Redfern, S. A. T.

    2015-12-01

    The KP province of Pakistan hosts widespread deposits of thermo-metamorphic marbles that were extensively used as a building and ornamental stones since the time of earliest flourishing civilization in this region known as Indus Valley Civilization (2500 BC). The macroscopic characteristics of 22 marble varieties collected from three different areas of Lesser Himalayas (Northwest Pakistan), its chemical, mineralogical, petrographic features, temperature conditions of metamorphic re-crystallization, and the main physical properties are presented in order to provide a solid basis for possible studies on the provenance and distribution of building stones from this region. The results provide a set of diagnostic parameters that allow discriminating the investigated marbles and quarries. Studied marbles overlap in major phase assemblage, but the accessory mineral content, chemistry, the maximum grain size (MGS) and other petrographic characteristics are particularly useful in the distinction between them. On the basis of macroscopic features, the studied marbles can be classifies into four groups: (i) white (ii) grey-to-brown veined, (iii) brown-reddish to yellowish and (iv) dark-grey to blackish veined marbles. The results show that the investigated marbles are highly heterogeneous in both their geochemical parameters and minero-petrographic features. Microscopically, the white, grey-to-brown and dark-grey to blackish marbles display homeoblastic/granoblastic texture, and the brown-reddish to yellowish marbles display a heteroblastic texture with traces of slightly deformed polysynthetic twining planes. Minero-petrography, XRD, SEM and EPMA revealed that the investigated marbles chiefly consist of calcite along with dolomite, quartz, muscovite, pyrite, K-feldspar, Mg, Ti and Fe-oxides as subordinates. The magnesium content of calcite coexisting with dolomite was estimated by both XRD and EPMA/EDS, indicating the metamorphic temperature of re-crystallization from 414

  18. Magnetic mapping for structural geology and geothermal exploration in Guadeloupe, Lesser Antilles

    Science.gov (United States)

    Mercier de Lépinay, jeanne; munschy, marc; geraud, yves; diraison, marc; navelot, vivien; verati, christelle; corsini, michel; lardeaux, jean marc; favier, alexiane

    2017-04-01

    This work is implemented through the GEOTREF program which benefits from the support of both the ADEME and the French public funds "Investments for the future". The program focuses on the exploration for geothermal resources in Guadeloupe, Lesser Antilles, where a geothermal power plant is in production since 1986 (Bouillante, Basse Terre). In Les Saintes archipelago, in the south of Guadeloupe, the outcrop analysis of Terre-de-Haut Island allows to point out an exhumed geothermal paleo-system that is thought to be an analogue of the Bouillante active geothermal system. We show that a detailed marine magnetic survey with a quantitative interpretation can bring information about the offshore structures around Les Saintes archipelago in order to extend the geological limits and structural elements. A similar survey and workflow is also conducted offshore Basse-Terre where more geophysical data is already available. In order to correctly link the offshore and onshore structures, the magnetic survey must be close enough to the shoreline and sufficiently detailed to correctly outline the tectonic structures. An appropriate solution for such a survey is to use a three component magnetometer aboard a speedboat. Such a boat allows more navigation flexibility than a classic oceanic vessel towing a magnetometer; it can sail at higher speed on calm seas and closer to the shoreline. This kind of magnetic acquisition is only viable because the magnetic effect of the ship can be compensated using the same algorithms than those used for airborne magnetometry. The use of potential field transforms allows a large variety of structures to be highlighted, providing insights to build a general understanding of the nature and distribution of the magnetic sources. In particular, we use the tilt angle operator to better identify the magnetic lineaments offshore in order to compare them to the faults identified onshore during the outcrop analysis. All the major faults and fractures

  19. Transmission of Salmonella to broilers by contaminated larval and adult lesser mealworms, Alphitobius diaperinus (Coleoptera: Tenebrionidae).

    Science.gov (United States)

    Roche, A J; Cox, N A; Richardson, L J; Buhr, R J; Cason, J A; Fairchild, B D; Hinkle, N C

    2009-01-01

    The ability of the lesser mealworm, Alphitobius diaperinus (Panzer), commonly known as the darkling beetle, to transmit marker Salmonella Typhimurium to day-of-hatch broiler chicks was evaluated, as well as the spread to nonchallenged pen mates. In trial 1, day-of-hatch chicks were orally gavaged with 4 larval or 4 adult beetles that had been exposed to marker Salmonella-inoculated feed for 72 h. In addition, chicks were gavaged with the marker Salmonella in saline solution. These chicks were then placed into pens to serve as challenged broilers. In trial 2, all pens received 2 challenged chicks that were gavaged with larvae or beetles that had been exposed to marker Salmonella-inoculated feed for 24 h and then removed from the inoculated feed for a period of 7 d. At 3 wk of age, cecal samples from the marker Salmonella-challenged broilers and from 5 pen mates in trial 1, or 10 pen mates in trial 2, were evaluated for the presence of the marker Salmonella in their ceca, and at 6 wk of age, all remaining pen mates were sampled. To monitor the presence of the marker Salmonella within pens, stepped-on drag swab litter samples were taken weekly. For the Salmonella-saline pens, 29 to 33% of the broilers that had been challenged and 10 to 55% of the pen mates were positive at 3 wk of age, and only 2 to 6% had positive ceca at 6 wk. For the pens challenged with adult beetles, 0 to 57% of the challenged broilers and 20 to 40% of the pen mates had positive ceca at 3 wk, and 4 to 7% were positive at 6 wk. The pens challenged with larvae had the greatest percentage of marker Salmonella-positive broilers; 25 to 33% of the challenged broilers and 45 to 58% of pen mates were positive at 3 wk, and 11 to 27% were positive at 6 wk. These results demonstrated that ingestion of larval or adult beetles contaminated with a marker Salmonella could be a significant vector for transmission to broilers.

  20. Diagenesis in tephra-rich sediments from the Lesser Antilles Volcanic Arc: Pore fluid constraints

    Science.gov (United States)

    Murray, Natalie A.; McManus, James; Palmer, Martin R.; Haley, Brian; Manners, Hayley

    2018-05-01

    We present sediment pore fluid and sediment solid phase results obtained during IODP Expedition 340 from seven sites located within the Grenada Basin of the southern Lesser Antilles Volcanic Arc region. These sites are generally characterized as being low in organic carbon content and rich in calcium carbonate and volcanogenic material. In addition to the typical reactions related to organic matter diagenesis, pore fluid chemistry indicates that the diagenetic reactions fall within two broad categories; (1) reactions related to chemical exchange with volcanogenic material and (2) reactions related to carbonate dissolution, precipitation, or recrystallization. For locations dominated by reaction with volcanogenic material, these sites exhibit increases in dissolved Ca with coeval decreases in Mg. We interpret this behavior as being driven by sediment-water exchange reactions from the alteration of volcanic material that is dispersed throughout the sediment package, which likely result in formation of Mg-rich secondary authigenic clays. In contrast to this behavior, sediment sequences that exhibit decreases in Ca, Mg, Mn, and Sr with depth suggest that carbonate precipitation is an active diagenetic process affecting solute distributions. The distributions of pore fluid 87Sr/86Sr reflect these competitive diagenetic reactions between volcanic material and carbonate, which are inferred by the major cation distributions. From one site where we have solid phase 87Sr/86Sr (site U1396), the carbonate fraction is found to be generally consistent with the contemporaneous seawater isotope values. However, the 87Sr/86Sr of the non-carbonate fraction ranges from 0.7074 to 0.7052, and these values likely represent a mixture of local arc volcanic sources and trans-Atlantic eolian sources. Even at this site where there is clear evidence for diagenesis of volcanogenic material, carbonate diagenesis appears to buffer pore fluid 87Sr/86Sr from the larger changes that might be

  1. REX-1 expression and p38 MAPK activation status can determine proliferation/differentiation fates in human mesenchymal stem cells.

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    Dilli Ram Bhandari

    Full Text Available BACKGROUND: REX1/ZFP42 is a well-known embryonic stem cell (ESC marker. However, the role of REX1, itself, is relatively unknown because the function of REX1 has only been reported in the differentiation of ESCs via STAT signaling pathways. Human mesenchymal stem cells (hMSCs isolated from young tissues and cancer cells express REX1. METHODOLOGY/PRINCIPAL FINDING: Human umbilical cord blood-derived MSCs (hUCB-MSCs and adipose tissue-derived MSCs (hAD-MSCs strongly express REX1 and have a lower activation status of p38 MAPK, but bone marrow-derived MSCs (hBM-MSCs have weak REX1 expression and higher activation of p38 MAPK. These results indicated that REX1 expression in hMSCs was positively correlated with proliferation rates but inversely correlated with the phosphorylation of p38 MAPK. In hUCB-MSCs, the roles of REX1 and p38 MAPK were investigated, and a knockdown study was performed using a lentiviral vector-based small hairpin RNA (shRNA. After REX1 knockdown, decreased cell proliferation was observed. In REX1 knocked-down hUCB-MSCs, the osteogenic differentiation ability deteriorated, but the adipogenic potential increased or was similar to that observed in the controls. The phosphorylation of p38 MAPK in hUCB-MSCs significantly increased after REX1 knockdown. After p38 MAPK inhibitor treatment, the cell growth in REX1 knocked-down hUCB-MSCs almost recovered, and the suppressed expression levels of CDK2 and CCND1 were also restored. The expression of MKK3, an upstream regulator of p38 MAPK, significantly increased in REX1 knocked-down hUCB-MSCs. The direct binding of REX1 to the MKK3 gene was confirmed by a chromatin immunoprecipitation (ChIP assay. CONCLUSIONS/SIGNIFICANCE: These findings showed that REX1 regulates the proliferation/differentiation of hMSCs through the suppression of p38 MAPK signaling via the direct suppression of MKK3. Therefore, p38 MAPK and REX-1 status can determine the cell fate of adult stem cells (ASCs. These

  2. Transforming growth factor β recruits persistent MAPK signaling to regulate long-term memory consolidation in Aplysia californica.

    Science.gov (United States)

    Shobe, Justin; Philips, Gary T; Carew, Thomas J

    2016-05-01

    In this study, we explore the mechanistic relationship between growth factor signaling and kinase activity that supports the protein synthesis-dependent phase of long-term memory (LTM) consolidation for sensitization ofAplysia Specifically, we examine LTM for tail shock-induced sensitization of the tail-elicited siphon withdrawal (T-SW) reflex, a form of memory that requires both (i) extracellular signal-regulated kinase (ERK1/2; MAPK) activity within identified sensory neurons (SNs) that mediate the T-SW and (ii) the activation of transforming growth factor β (TGFβ) signaling. We now report that repeated tail shocks that induce intermediate-term (ITM) and LTM for sensitization, also induce a sustained post-training phase of MAPK activity in SNs (lasting at least 1 h). We identified two mechanistically distinct phases of post-training MAPK: (i) an immediate phase that does not require ongoing protein synthesis or TGFβ signaling, and (ii) a sustained phase that requires both protein synthesis and extracellular TGFβ signaling. We find that LTM consolidation requires sustained MAPK, and is disrupted by inhibitors of protein synthesis and TGFβ signaling during the consolidation window. These results provide strong evidence that TGFβ signaling sustains MAPK activity as an essential mechanistic step for LTM consolidation. © 2016 Shobe et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Effect of Repeated Electroacupuncture Intervention on Hippocampal ERK and p38MAPK Signaling in Neuropathic Pain Rats

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    Jun-ying Wang

    2015-01-01

    Full Text Available Results of our past studies showed that hippocampal muscarinic acetylcholine receptor (mAChR-1 mRNA and differentially expressed proteins participating in MAPK signaling were involved in electroacupuncture (EA induced cumulative analgesia in neuropathic pain rats, but the underlying intracellular mechanism remains unknown. The present study was designed to observe the effect of EA stimulation (EAS on hippocampal extracellular signal-regulated kinases (ERK and p38 MAPK signaling in rats with chronic constrictive injury (CCI of the sciatic nerve, so as to reveal its related intracellular targets in pain relief. After CCI, the thermal pain thresholds of the affected hind were significantly decreased compared with the control group (P<0.05. Following one and two weeks’ EAS of ST 36-GB34, the pain thresholds were significantly upregulated (P<0.05, and the effect of EA2W was remarkably superior to that of EA2D and EA1W (P<0.05. Correspondingly, CCI-induced decreased expression levels of Ras, c-Raf, ERK1 and p-ERK1/2 proteins, and p38 MAPK mRNA and p-p38MAPK protein in the hippocampus tissues were reversed by EA2W (P<0.05. The above mentioned results indicated that EA2W induced cumulative analgesic effect may be closely associated with its function in removing neuropathic pain induced suppression of intracellular ERK and p38MAPK signaling in the hippocampus.

  4. MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kazuyo [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Kuroda, Takafumi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Takaya, Akari; Kubo, Terufumi; Kanaseki, Takayuki; Tsukahara, Tomohide [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hasegawa, Tadashi [Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Saito, Tsuyoshi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Sato, Noriyuki [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Torigoe, Toshihiko, E-mail: torigoe@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan)

    2016-04-15

    Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

  5. p38 Mitogen Activated Protein Kinase (MAPK): A New Therapeutic Target for Reducing the Risk of Adverse Pregnancy Outcomes

    Science.gov (United States)

    Menon, Ramkumar; Papaconstantinou, John

    2016-01-01

    Introduction Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert Opinion This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation and its functional effects. PMID:27459026

  6. Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation.

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    Ling-Yun Chu

    Full Text Available The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs prevented endothelial hyperpermeability and VE-cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK.

  7. [Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway].

    Science.gov (United States)

    Ejarque, Ismael; Millán-Salvador, José M; Oltra, Silvestre; Pesudo-Martínez, José V; Beneyto, Magdalena; Pérez-Aytés, Antonio

    2015-05-01

    Noonan syndrome (NS) and other syndromes with a similar phenotype, such as LEOPARD, cardiofaciocutaneous, Costello and Legius, are associated to mutations in genes included in the RAS/MAPK pathway (RASopathies), which is an important signalling pathway related to cell proliferation. Tonsillar descent into the upper cervical spinal canal, known as Arnold-Chiari malformation (ACM), has been reported in patients with NS and this has led some researchers to suggest that ACM could be part of the phenotypic spectrum of NS. We report two cases of NS and ACM. Case 1: 29-year-old female with Noonan phenotype who underwent surgery at the age of nine years due to pulmonary valve stenosis. At the age of 27, she presented symptomatic ACM that required surgical decompression. She presented the c.922A>G (N308D) mutation in the gene PTPN that belongs to the RAS/MAPK pathway. Case 2: a 10-year-old female with Noonan phenotype and asymptomatic ACM detected in magnetic resonance imaging of the brain. She was a carrier of the c.923A>G (N308S) mutation in gene PTPN11. Six patients with this association have been found in the literature, four with the Noonan phenotype and two with LEOPARD. Our two patients provide supplementary evidence that backs up the hypothesis by which ACM would be part of the phenotypic spectrum of NS. The small number of reported cases of patients with this association does not allow us to draw up recommendations about when and how often neuroimaging studies should be performed; a careful neurological examination, however, should be included in the anticipatory health guidelines in syndromes involving the RAS/MAPK pathway.

  8. Acidic environment leads to ROS-induced MAPK signaling in cancer cells.

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    Anne Riemann

    Full Text Available Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e, pH(i and mitogen-activated-protein-kinases (ERK1/2, p38 was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furthermore, p38 phosphorylation was elicited by sole intracellular lactacidosis at normal pH(e. Inhibition of ERK1/2 phosphorylation during acidosis led to necrotic cell death. No evidence for the involvement of the kinases c-SRC, PKC, PKA, PI3K or EGFR nor changes in cell volume in acidosis-induced MAPK activation was obtained. However, our data reveal that acidosis enhances the formation of reactive oxygen species (ROS, probably originating from mitochondria, which subsequently trigger MAPK phosphorylation. Scavenging of ROS prevented acidosis-induced MAPK phosphorylation whereas addition of H(2O(2 enhanced it. Finally, acidosis increased phosphorylation of the transcription factor CREB via p38, leading to increased transcriptional activity of a CRE-reporter even 24 h after switching the cells back to a normal environmental milieu. Thus, an acidic tumor microenvironment can induce a longer lasting p38-CREB-medited change in the transcriptional program, which may maintain the altered phenotype even when the cells leave the tumor environment.

  9. Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption.

    Science.gov (United States)

    Ghasemi, Rasoul; Zarifkar, Asadollah; Rastegar, Karim; maghsoudi, Nader; Moosavi, Maryam

    2014-10-01

    Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of beta amyloid (Aβ) and neuronal loss particularly in the hippocampus. Accumulating evidences have implied that insulin signaling impairment plays a key role in the pathology of AD; as much as it is considered as type 3 Diabetes. MAPKs are a group of signaling molecules which are involved in pathobiology of AD. Therefore this study was designed to investigate if intrahippocampal insulin hinders Aβ-related memory deterioration, hippocampal apoptosis and MAPKs signaling alteration induced by Aβ. Adult male Sprague-Dawely rats weighing 250-300 g were used in this study. The canules were implanted bilaterally into CA1 region. Aβ25-35 was administered during first 4 days after surgery (5 μg/2.5 μL/daily). Insulin treatment (0.5 or 6 mU) was done during days 4-9. The animal's learning and memory capability was assessed on days 10-13 using Morris water maze. After finishing of behavioral studies the hippocampi was isolated and the amount of hippocampal cleaved caspase 3 (the landmark of apoptosis) and the phosphorylated (activated) forms of P38, JNK and ERK was analyzed by western blot. The results showed that insulin in 6 but not 0.5 mU reversed the memory loss induced by Aβ25-35. Western blot analysis revealed that Aβ25-35 induced elevation of caspase-3 and all 3 MAPks subfamily activity, while insulin in 6 mu restored ERK and P38 activation but has no effect on JNK. This study disclosed that intrahippocampal insulin treatment averts not only Aβ-induced memory deterioration but also hippocampal caspase-3, ERK and P38 activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Stepwise metamorphosis of the tubeworm Hydroides elegans is mediated by a bacterial inducer and MAPK signaling.

    Science.gov (United States)

    Shikuma, Nicholas J; Antoshechkin, Igor; Medeiros, João M; Pilhofer, Martin; Newman, Dianne K

    2016-09-06

    Diverse animal taxa metamorphose between larval and juvenile phases in response to bacteria. Although bacteria-induced metamorphosis is widespread among metazoans, little is known about the molecular changes that occur in the animal upon stimulation by bacteria. Larvae of the tubeworm Hydroides elegans metamorphose in response to surface-bound Pseudoalteromonas luteoviolacea bacteria, producing ordered arrays of phage tail-like metamorphosis-associated contractile structures (MACs). Sequencing the Hydroides genome and transcripts during five developmental stages revealed that MACs induce the regulation of groups of genes important for tissue remodeling, innate immunity, and mitogen-activated protein kinase (MAPK) signaling. Using two MAC mutations that block P. luteoviolacea from inducing settlement or metamorphosis and three MAPK inhibitors, we established a sequence of bacteria-induced metamorphic events: MACs induce larval settlement; then, particular properties of MACs encoded by a specific locus in P. luteoviolacea initiate cilia loss and activate metamorphosis-associated transcription; finally, signaling through p38 and c-Jun N-terminal kinase (JNK) MAPK pathways alters gene expression and leads to morphological changes upon initiation of metamorphosis. Our results reveal that the intricate interaction between Hydroides and P. luteoviolacea can be dissected using genomic, genetic, and pharmacological tools. Hydroides' dependency on bacteria for metamorphosis highlights the importance of external stimuli to orchestrate animal development. The conservation of Hydroides genome content with distantly related deuterostomes (urchins, sea squirts, and humans) suggests that mechanisms of bacteria-induced metamorphosis in Hydroides may have conserved features in diverse animals. As a major biofouling agent, insight into the triggers of Hydroides metamorphosis might lead to practical strategies for fouling control.

  11. Reconstructed North American Snow Extent, 1900-1993

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains reconstructed monthly North American snow extent values for November through March, 1900-1993. Investigators used a combination of satellite...

  12. Exploring the extent to which ELT students utilise smartphones for ...

    African Journals Online (AJOL)

    Zehra

    2015-11-09

    Nov 9, 2015 ... aimed to explore the extent to which English Language Teaching (ELT) students utilise ... Given the fact that almost all students have a personal smartphone, and use it ..... ears as a disadvantage for smartphones (Kétyi,.

  13. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

    Directory of Open Access Journals (Sweden)

    Yuan Ma

    2016-01-01

    Full Text Available Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA- sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs were challenged by tumor necrosis factor alpha (TNF-α. The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS/mitogen-activated protein kinase (MAPK evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL- 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2′,7′-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were

  14. Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.

    Directory of Open Access Journals (Sweden)

    Marc Amoyel

    2016-01-01

    Full Text Available The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs, which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs, which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.

  15. Radiological evaluation of subjects submitted to vagotomy, antrectomy and gastroduodenal anastomosis at the lesser curvature in chlorydropeptic ulceration

    International Nuclear Information System (INIS)

    Silva, A.L.; Petroianu, A.; Ferreira, C.S.

    1988-01-01

    This work shows a radiologic study of stomachs operated for chlorydropeptic ulceration by the surgical technique of: vagotomy, antrectomy and gastroduodenal anastomosis at the lesser curvature. Our objective was to observe the gastric morphology and motility turned to its emptying. The results suggested good perspectives, mainly, in the late post-operative. The operated stomachs get a similar morphology with the normal one and its emptying, at first, slow, tended to normalize. (author) [pt

  16. Determination of the elemental composition of some lesser-used Ghanaian wood species by neutron activation analysis

    International Nuclear Information System (INIS)

    Nyarko, B.J.B.; Serfor-Armah, Y.; Adomako, D.; Andam, A.A.B.; Addison, E.C.K.; Ofori, J.; Cobbinah, J.R.

    2003-01-01

    Wood plays an undisputed socio-economic role in human endeavour. The elemental composition of wood can give an indication of the environmental pollution of the locality from which the wood sample was extracted as timber, and can influence the machining characteristics of timber. Additionally, the elemental composition can be used as an index of the nutrient uptake of plants from the soil. With the over-exploitation of timber species in Ghana, it is now imperative that lesser-used species are studied to know their characteristics for utilization. We report preliminary results of a study on the elemental composition of some lesser-used Ghanaian wood species. Ten Ghana wood species had been studied, namely: Strombosia glauscens, Lophira alata, Cynometra anata, Combretodendron macrocarpum, Sterculia rhinopetala, Celtis milbraedii, Celtis zenteri, Nesogoadonia papaverifa, Nauclea diderrichii, and Piptadeniastrum afrieana. Neutron activation analysis was carried out for this work, using the Ghana Research Reactor, (GHARRI) facility, operating between 3-15kw and at a thermal neutron flux of 1-5 x 10 15 ns -1 cm 2 . A total of twenty-five elements were identified, some at high level, others at trace levels. We discuss the implications of these results for the efficient utilization of lesser-used Ghana wood species (author)

  17. Inhibition of MAPK and PKC pathways by 60Co γ-radiation in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Jia Guanghong; Ma Yexin; Xiao Jianming

    2002-01-01

    Objective: To investigate the signal transduction pathways inhibited by 60 Co γ-radiation in cultured vascular smooth muscle cells (VSMC). Methods: The cultured VSMC were irradiated with 60 Co γ-radiation of 3.5, 7.0 and 14 Gy respectively. VSMC proliferation was measured by 3 H-TdR incorporation, while PKC, MAPK activities were determined by radioactivity assay. Results: Proliferation of VSMC was inhibited by 7.0, 14 Gy 60 Co γ-irradiation and the activities of PKC, MAPK were decreased significantly. Conclusion: Inhibitory effect of 7.0, 14 Gy 60 Co γ-irradiation on proliferation of VSMC might be resulted from decrease of the activity of PKC, MAPK

  18. Lesser Antillean Arc Initiation and Migration as a Proxy of Slab Dynamics: Geothermochronology, Thermobarometry and Structure of Saint Martin Granodiorites

    Science.gov (United States)

    Noury, M.; Münch, P.; Philippon, M. M.; Bernet, M.; Bruguier, O.; Balvay, M.

    2017-12-01

    In subduction zones, volcanic arc initiation, cessation, migration and associated upper plate deformation -i.e faulting and vertical motions- reflect large-scale slab dynamics. At the northeastern edge of the Caribbean plate, the Greater Caribbean subduction zone waned out during the Mid Eocene, following the subduction of the Bahamas bank. This arc cessation was contemporaneous with (i) a plate boundary re-organization (evolving from subduction to transform), (ii) upper plate deformation and (iii) arc initiation in the Lesser Antilles. As part of the GAARANTI project that aims at unraveling the relationships between the evolution of terrestrial Caribbean biodiversity and vertical motions resulting from the Lesser Antilles subduction zone dynamic, we study the Saint Martin granodiorites, one of the two Oligocene plutons outcropping in the Lesser Antillean forearc. We investigate the birth and evolution of the Lesser Antillean arc and its thermo-mechanical impact on the Caribbean upper plate. In order to characterize the P,T,t path of the pluton we performed several thermochronological analyses covering a wide range of temperature (U-Pb on zircon -Tc 850°C, Ar/Ar on amphibole -Tc 550°C- and biotite -Tc 325°C-, zircon and apatite fission-tracks -Tc 250 and 110°C, respectively as well as U-Th/He on apatite -Tc 60°C) coupled with in-situ thermobarometry analyses (Al in hornblendes) and structural data. Geochronology and thermobarometry reveal that the granodiorites emplaced at ca. 28 Ma, at a depth of 5 km. Based on the age difference between amphibole and biotite Ar/Ar ages, we show that the northern pluton cooled faster than the southern one. Preliminary thermochronological results show a fast cooling between 29 and 25 Ma and then a continuous and slow cooling since 25 Ma and inverse modeling points to a 10 Ma cooling event. Our investigations give insights on the thermo-mechanical evolution of the arc-forearc region of the Lesser Antilles subduction zone

  19. PKR is a novel functional direct player that coordinates skeletal muscle differentiation via p38MAPK/AKT pathways.

    Science.gov (United States)

    Alisi, A; Spaziani, A; Anticoli, S; Ghidinelli, M; Balsano, C

    2008-03-01

    Myogenic differentiation is a highly orchestrated multistep process controlled by extracellular growth factors that modulate largely unknown signals into the cell affecting the muscle-transcription program. P38MAPK-dependent signalling, as well as PI3K/Akt pathway, has a key role in the control of muscle gene expression at different stages during the myogenic process. P38MAPK affects the activities of transcription factors, such as MyoD and myogenin, and contributes, together with PI3K/Akt pathway, to control the early and late steps of myogenic differentiation. The aim of our work was to better define the role of PKR, a dsRNA-activated protein kinase, as potential component in the differentiation program of C2C12 murine myogenic cells and to correlate its activity with p38MAPK and PI3K/Akt myogenic regulatory pathways. Here, we demonstrate that PKR is an essential component of the muscle development machinery and forms a functional complex with p38MAPK and/or Akt, contributing to muscle differentiation of committed myogenic cells in vitro. Inhibition of endogenous PKR activity by a specific (si)RNA and a PKR dominant-negative interferes with the myogenic program of C2C12 cells, causing a delay in activation of myogenic specific genes and inducing the formation of thinner myofibers. In addition, the construction of three PKR mutants allowed us to demonstrate that both N and C-terminal regions of PKR are critical for the interaction with p38MAPK and Akt. The novel discovered complex permits PKR to timely regulate the inhibition/activation of p38MAPK and Akt, controlling in this way the different steps characterizing skeletal muscle differentiation.

  20. Estrogen Enhances Matrix Synthesis in Nucleus Pulposus Cell through the Estrogen Receptor β-p38 MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Pei Li

    2016-11-01

    Full Text Available Background/Aims: Matrix homeostasis within the disc nucleus pulposus (NP tissue is important for disc function. Increasing evidence indicates that sex hormone can influence the severity of disc degeneration. This study was aimed to study the role of 17β-estradiol (E2 in NP matrix synthesis and its underlying mechanism. Methods: Rat NP cells were cultured with (10-5, 10-7 and 10-9 M or without (control E2 for48 hours. The estrogen receptor (ER-β antagonist PHTPP and ERβ agonist ERB 041 were used to investigate the role mediated by ERβ. The p38 MAPK inhibitor SB203580 was used to investigate the role of p38 MAPK signaling pathway. Gene and protein expression of SOX9, aggrecan and collagen II, glycosaminoglycan (GAG content, and immunostaining assay for aggrecan and collagen II were analyzed to evaluate matrix production in rat NP cells. Results: E2 enhanced NP matrix synthesis in a concentration-dependent manner regarding gene and proetin expression of SOX9, aggrecan and collagen II, protein deposition of aggrecan and collagen II, and GAG content. Moreover, activation of p38 MAPK signaling pathway was increased with elevating E2 concentration. Further analysis indicated that ERB 041 and PHTPP could respectively enhance and suppress effects of E2 on matrix synthesis in NP cells, as well as activation of p38 MAPK pathway. Additionally, inhibition of p38 MAPK signaling pathway significantly abolished the effects of E2 on matrix synthesis. Conclusion: E2 can enhance matrix synthesis of NP cells and the ERβ/p38 MAPK pathway is involved in this regulatory process.

  1. Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity.

    Science.gov (United States)

    Tong, Jiefei; Elowe, Sabine; Nash, Piers; Pawson, Tony

    2003-02-21

    Signaling by the Eph family of receptor tyrosine kinases (RTKs) is complex, because they can interact with a variety of intracellular targets, and can potentially induce distinct responses in different cell types. In NG108 neuronal cells, activated EphB2 recruits p120RasGAP, in a fashion that is associated with down-regulation of the Ras-Erk mitogen-activated kinase (MAPK) pathway and neurite retraction. To pursue the role of the Ras-MAPK pathway in EphB2-mediated growth cone collapse, and to explore the biochemical and biological functions of Eph receptors, we sought to re-engineer the signaling properties of EphB2 by manipulating its regulatory motifs and SH2 binding sites. An EphB2 mutant that retained juxtamembrane (JM) RasGAP binding sites but incorporated a Grb2 binding motif at an alternate RasGAP binding site within the kinase domain had little effect on basal Erk MAPK activation. In contrast, elimination of all RasGAP binding sites, accompanied by the addition of a Grb2 binding site within the kinase domain, led to an increase in phospho-Erk levels in NG108 cells following ephrin-B1 stimulation. Functional assays indicated a correlation between neurite retraction and the ability of the EphB2 mutants to down-regulate Ras-Erk MAPK signaling. These data suggest that EphB2 can be designed to repress, stabilize, or activate the Ras-Erk MAPK pathway by the manipulation of RasGAP and Grb2 SH2 domain binding sites and support the notion that Erk MAPK regulation plays a significant role in axon guidance. The behavior of EphB2 variants with mutations in the JM region and kinase domains suggests an intricate pattern of regulation and target recognition by Eph receptors.

  2. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

    Science.gov (United States)

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2015-10-01

    Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  3. ROS generation and MAPKs activation contribute to the Ni-induced testosterone synthesis disturbance in rat Leydig cells.

    Science.gov (United States)

    Han, Aijie; Zou, Lingyue; Gan, Xiaoqin; Li, Yu; Liu, Fangfang; Chang, Xuhong; Zhang, Xiaotian; Tian, Minmin; Li, Sheng; Su, Li; Sun, Yingbiao

    2018-06-15

    Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testosterone production and ROS levels were detected in Leydig cells. The mRNA and protein levels of testosterone synthetase, including StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD, were determined. Effects of Ni on the ERK1/2, p38 and JNK MAPKs were also investigated. The results showed that Ni triggered ROS generation, consequently resulted in the decrease of testosterone synthetase expression and testosterone production in Leydig cells, which were then attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels and testosterone secretion were all alleviated by co-treatment with MAPK specific inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in Leydig cells. In conclusion, these findings suggest that Ni causes testosterone synthesis disorder, partly, via ROS and MAPK signal pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Characterization of early events involved in human dendritic cell maturation induced by sensitizers: Cross talk between MAPK signalling pathways

    International Nuclear Information System (INIS)

    Trompezinski, Sandra; Migdal, Camille; Tailhardat, Magalie; Le Varlet, Beatrice; Courtellemont, Pascal; Haftek, Marek; Serres, Mireille

    2008-01-01

    Dendritic cells (DCs), efficient-antigen presenting cells play an important role in initiating and regulating immune responses. DC maturation following exposure to nickel or DNCB induced an up-regulation of phenotypic markers and inflammatory cytokine secretion. Early intracellular mechanisms involved in DC maturation required to be precise. To address this purpose, DCs derived from human monocytes were treated with sensitizers (nickel, DNCB or thimerosal) in comparison with an irritant (SDS). Our data confirming the up-regulation of CD86, CD54 and cytokine secretion (IL-8 and TNFα) induced by sensitizers but not by SDS, signalling transduction involved in DC maturation was investigated using these chemicals. Kinase activity measurement was assessed using two new sensitive procedures (Face TM and CBA) requiring few cells. SDS did not induce changes in signalling pathways whereas NiSO 4 , DNCB and thimerosal markedly activated p38 MAPK and JNK, in contrast Erk1/2 phosphorylation was completely inhibited by DNCB or thimerosal and only activated by nickel. A pre-treatment with p38 MAPK inhibitor (SB203580) suppressed Erk1/2 inhibition induced by DNCB or thimerosal demonstrating a direct interaction between p38 MAPK and Erk1/2. A pre-treatment with an antioxidant, N-acetyl-L-cysteine (NAC) markedly reduced Erk1/2 inhibition and p38 MAPK phosphorylation induced by DNCB and thimerosal, suggesting a direct activation of p38 MAPK via an oxidative stress and a regulation of MAPK signalling pathways depending on chemicals. Because of a high sensitivity of kinase activity measurements, these procedures will be suitable for weak or moderate sensitizer screening

  5. Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells.

    Science.gov (United States)

    Cato, Anita; Celada, Lindsay; Kibakaya, Esther Caroline; Simmons, Nadia; Whalen, Margaret M

    2014-12-01

    Natural killer (NK) cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. In previous studies, we have shown that other environmental contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAPK kinases (MAP2Ks). The effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs (p44/42, p38, and JNK) and the phosphorylation and total levels of the MAP2Ks (MEK1/2 and MKK3/6) were examined. Results indicate that exposure of human NK cells to 10-0.5 μM HBCD or TBBPA activate MAPKs and MAP2Ks. This HBCD and TBBPA-induced activation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA.

  6. Differential roles of PKC isoforms (PKCs) in GnRH stimulation of MAPK phosphorylation in gonadotrope derived cells.

    Science.gov (United States)

    Mugami, Shany; Dobkin-Bekman, Masha; Rahamim-Ben Navi, Liat; Naor, Zvi

    2018-03-05

    The role of protein kinase C (PKC) isoforms (PKCs) in GnRH-stimulated MAPK [ERK1/2, JNK1/2 and p38) phosphorylation was examined in gonadotrope derived cells. GnRH induced a protracted activation of ERK1/2 and a slower and more transient activation of JNK1/2 and p38MAPK. Gonadotropes express conventional PKCα and PKCβII, novel PKCδ, PKCε and PKCθ, and atypical PKC-ι/λ. The use of green fluorescent protein (GFP)-PKCs constructs revealed that GnRH induced rapid translocation of PKCα and PKCβII to the plasma membrane, followed by their redistribution to the cytosol. PKCδ and PKCε localized to the cytoplasm and Golgi, followed by the rapid redistribution by GnRH of PKCδ to the perinuclear zone and of PKCε to the plasma membrane. The use of dominant negatives for PKCs and peptide inhibitors for the receptors for activated C kinase (RACKs) has revealed differential role for PKCα, PKCβII, PKCδ and PKCε in ERK1/2, JNK1/2 and p38MAPK phosphorylation in a ligand-and cell context-dependent manner. The paradoxical findings that PKCs activated by GnRH and PMA play a differential role in MAPKs phosphorylation may be explained by persistent vs. transient redistribution of selected PKCs or redistribution of a given PKC to the perinuclear zone vs. the plasma membrane. Thus, we have identified the PKCs involved in GnRH stimulated MAPKs phosphorylation in gonadotrope derived cells. Once activated, the MAPKs will mediate the transcription of the gonadotropin subunits and GnRH receptor genes. Copyright © 2017. Published by Elsevier B.V.

  7. Arsenic trioxide inhibits Ewing's sarcoma cell invasiveness by targeting p38(MAPK) and c-Jun N-terminal kinase.

    Science.gov (United States)

    Zhang, Shuai; Guo, Wei; Ren, Ting-Ting; Lu, Xin-Chang; Tang, Guo-Qing; Zhao, Fu-Long

    2012-01-01

    Ewing's sarcoma is the second most frequent primary malignant bone tumor, mainly affecting children and young adults. The notorious metastatic capability of this tumor aggravates patient mortality and remains a problem to be overcome. We investigated the effect of arsenic trioxide (As₂O₃) on the metastasis capability of Ewing's sarcoma cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide assays to choose appropriate concentrations of As₂O₃ for the experiments. Migration, invasion, and adhesion assays were performed to assess the effect of As₂O₃ on the metastasis of Ewing's sarcoma. Immunofluorescent staining was used to observe cytoskeleton reorganization in Ewing's sarcoma cells treated with As₂O₃. Changes in matrix metalloproteinase-9 expression and the mitogen-activated protein kinase (MAPK) pathway were investigated using western blot. Inhibitors of p38(MAPK) (sb202190) and c-Jun NH₂-terminal kinase (JNK, sp600125) were used in invasion assays to determine the effect of p38(MAPK) and JNK. We found that As₂O₃ may markedly inhibit the migration and invasion capacity of Ewing's sarcoma cells with structural rearrangements of the actin cytoskeleton. The expressions of matrix metalloproteinase-9, phosphor-p38(MAPK), and phosphor-JNK were suppressed by As₂O₃ treatment in a dose-dependent manner. The inhibitors of p38(MAPK) (sb202190) and JNK (sp600125) enhanced the inhibition induced by As₂O₃, which was counteracted by anisomycin, an activating agent of p38(MAPK) and JNK. Taken together, our results demonstrate that As₂O₃ can inhibit the metastasis capability of RD-ES and A-673 cells and may have new therapeutic value for Ewing's sarcoma.

  8. Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway.

    Science.gov (United States)

    Chen, Xiang-Yan; Zhou, Jie; Luo, Li-Ping; Han, Bin; Li, Fei; Chen, Jing-Yao; Zhu, Yan-Feng; Chen, Wei; Yu, Xiao-Ping

    2015-01-01

    Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2(+) breast cancer cells. Treatment of MDA-MB-453 cells (HER2(+)) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression of raf, mek, and jnk. Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.

  9. LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase pathways

    International Nuclear Information System (INIS)

    Tong, W.-G.; Ding, X.-Z.; Talamonti, Mark S.; Bell, Richard H.; Adrian, Thomas E.

    2005-01-01

    We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4 receptor antagonists block growth and induce apoptosis in pancreatic cancer cells both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4 stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human pancreatic cancer cells, as measured by thymidine incorporation and cell number. LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38 MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not involved

  10. Vulnerability to glutamate toxicity of dopaminergic neurons is dependent on endogenous dopamine and MAPK activation.

    Science.gov (United States)

    Izumi, Yasuhiko; Yamamoto, Noriyuki; Matsuo, Takaaki; Wakita, Seiko; Takeuchi, Hiroki; Kume, Toshiaki; Katsuki, Hiroshi; Sawada, Hideyuki; Akaike, Akinori

    2009-07-01

    Dopaminergic neurons are more vulnerable than other types of neurons in cases of Parkinson disease and ischemic brain disease. An increasing amount of evidence suggests that endogenous dopamine plays a role in the vulnerability of dopaminergic neurons. Although glutamate toxicity contributes to the pathogenesis of these disorders, the sensitivity of dopaminergic neurons to glutamate toxicity has not been clarified. In this study, we demonstrated that dopaminergic neurons were preferentially affected by glutamate toxicity in rat mesencephalic cultures. Glutamate toxicity in dopaminergic neurons was blocked by inhibiting extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK. Furthermore, depletion of dopamine by alpha-methyl-dl-p-tyrosine methyl ester (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), protected dopaminergic neurons from the neurotoxicity. Exposure to glutamate facilitated phosphoryration of TH at Ser31 by ERK, which contributes to the increased TH activity. Inhibition of ERK had no additive effect on the protection offered by alpha-MT, whereas alpha-MT and c-jun N-terminal kinase or p38 MAPK inhibitors had additive effects and yielded full protection. These data suggest that endogenous dopamine is responsible for the vulnerability to glutamate toxicity of dopaminergic neurons and one of the mechanisms may be an enhancement of dopamine synthesis mediated by ERK.

  11. CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Li [Department of Pharmacy, Urumchi General Hospital of Lanzhou Military Region, Urumchi, Xinjiang 830000 (China); Liu, Lianyong [Medical College of Soochow University, Suzhou, Jiangsu 215123 (China); Department of Endocrinology, Shanghai Punan Hospital, Shanghai 200125 (China); He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang [Department of Endocrinology, Urumchi General Hospital of Lanzhou Military Region, Urumchi, Xinjiang 830000 (China); Tian, Jianqing, E-mail: jianqing0991@163.com [Department of Endocrinology, Urumchi General Hospital of Lanzhou Military Region, Urumchi, Xinjiang 830000 (China)

    2016-08-26

    The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. - Highlights: • CHIP is significantly upregulated in thyroid cancer cells. • Overexpression of CHIP facilitates proliferation and tumorigenesis of thyroid cancer cells. • Silencing of CHIP inhibits the proliferation and tumorigenesis of thyroid cancer cells. • CHIP promotes thyroid cancer cell proliferation via activating the MAPK and AKT pathways.

  12. p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion*

    Science.gov (United States)

    Greenblatt, Matthew B.; Kim, Jung-Min; Oh, Hwanhee; Park, Kwang Hwan; Choo, Min-Kyung; Sano, Yasuyo; Tye, Coralee E.; Skobe, Ziedonis; Davis, Roger J.; Park, Jin Mo; Bei, Marianna; Glimcher, Laurie H.; Shim, Jae-Hyuck

    2015-01-01

    An improved understanding of the molecular pathways that drive tooth morphogenesis and enamel secretion is needed to generate teeth from organ cultures for therapeutic implantation or to determine the pathogenesis of primary disorders of dentition (Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J. L. (1997) J. Biol. Chem. 272, 27678–27685). Here we present a novel ectodermal dysplasia phenotype associated with conditional deletion of p38α MAPK in ectodermal appendages using K14-cre mice (p38αK14 mice). These mice display impaired patterning of dental cusps and a profound defect in the production and biomechanical strength of dental enamel because of defects in ameloblast differentiation and activity. In the absence of p38α, expression of amelogenin and β4-integrin in ameloblasts and p21 in the enamel knot was significantly reduced. Mice lacking the MAP2K MKK6, but not mice lacking MAP2K MKK3, also show the enamel defects, implying that MKK6 functions as an upstream kinase of p38α in ectodermal appendages. Lastly, stimulation with BMP2/7 in both explant culture and an ameloblast cell line confirm that p38α functions downstream of BMPs in this context. Thus, BMP-induced activation of the p38α MAPK pathway is critical for the morphogenesis of tooth cusps and the secretion of dental enamel. PMID:25406311

  13. SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival

    Science.gov (United States)

    Becatti, Matteo; Fiorillo, Claudia; Barygina, Victoria; Cecchi, Cristina; Lotti, Torello; Prignano, Francesca; Silvestro, Agrippino; Nassi, Paolo; Taddei, Niccolò

    2014-01-01

    Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins (silent mating type information regulation 2 homolog) 1, well-known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage. PMID:24410795

  14. Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration.

    Science.gov (United States)

    Missinato, Maria A; Saydmohammed, Manush; Zuppo, Daniel A; Rao, Krithika S; Opie, Graham W; Kühn, Bernhard; Tsang, Michael

    2018-03-06

    Zebrafish regenerate cardiac tissue through proliferation of pre-existing cardiomyocytes and neovascularization. Secreted growth factors such as FGFs, IGF, PDGFs and Neuregulin play essential roles in stimulating cardiomyocyte proliferation. These factors activate the Ras/MAPK pathway, which is tightly controlled by the feedback attenuator Dual specificity phosphatase 6 (Dusp6), an ERK phosphatase. Here, we show that suppressing Dusp6 function enhances cardiac regeneration. Inactivation of Dusp6 by small molecules or by gene inactivation increased cardiomyocyte proliferation, coronary angiogenesis, and reduced fibrosis after ventricular resection. Inhibition of Erbb or PDGF receptor signaling suppressed cardiac regeneration in wild-type zebrafish, but had a milder effect on regeneration in dusp6 mutants. Moreover, in rat primary cardiomyocytes, NRG1-stimulated proliferation can be enhanced upon chemical inhibition of Dusp6 with BCI. Our results suggest that Dusp6 attenuates Ras/MAPK signaling during regeneration and that suppressing Dusp6 can enhance cardiac repair. © 2018. Published by The Company of Biologists Ltd.

  15. Molecular Mechanisms of Liver Injury and Hepatocarcinogenesis: Focusing on the Role of Stress-Activated MAPK

    Directory of Open Access Journals (Sweden)

    Hayato Nakagawa

    2012-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third most common cause of cancer mortality. Short-term prognosis of patients with HCC has improved recently due to advances in early diagnosis and treatment, but long-term prognosis is still unsatisfactory. Therefore, obtaining a further understanding of the molecular carcinogenic mechanisms and the unique pathogenic biology of HCC is important. The most characteristic process in hepatocarcinogenesis is underlying chronic liver injury, which leads to repeated cycles of hepatocyte death, inflammation, and compensatory proliferation and subsequently provides a mitogenic and mutagenic environment leading to the development of HCC. Recent in vivo studies have shown that the stress-activated mitogen-activated protein kinase (MAPK cascade converging on c-Jun NH2-terminal kinase (JNK and p38 plays a central role in these processes, and it has attracted considerable attention as a therapeutic target. However, JNK and p38 have complex functions and a wide range of cellular effects. In addition, crosstalk with each other and the nuclear factor-kappaB pathway further complicate these functions. A full understanding is essential to bring these observations into clinical settings. In this paper, we discuss the latest findings regarding the mechanisms of liver injury and hepatocarcinogenesis focusing on the role of the stress-activated MAPK pathway.

  16. The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling.

    Science.gov (United States)

    Hahn, Ines; Fuss, Bernhard; Peters, Annika; Werner, Tamara; Sieberg, Andrea; Gosejacob, Dominic; Hoch, Michael

    2013-06-01

    Guanine nucleotide exchange factors (GEFs) of the cytohesin protein family are regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf) of small GTPases. They have been identified as modulators of various receptor tyrosine kinase signaling pathways including the insulin, the vascular epidermal growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These pathways control many cellular functions, including cell proliferation and differentiation, and their misregulation is often associated with cancerogenesis. In vivo studies on cytohesins using genetic loss of function alleles are lacking, however, since knockout mouse models are not available yet. We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade. In the present study, we provide in vivo evidence for a role of Step in EGFR signaling during wing and eye development. By analyzing step mutants, transgenic RNA interference (RNAi) and overexpression lines for tissue specific as well as clonal analysis, we found that Step acts downstream of the EGFR and is required for the activation of mitogen-activated protein kinase (MAPK) and the induction of EGFR target genes. We further demonstrate that step transcription is induced by EGFR signaling whereas it is negatively regulated by insulin signaling. Furthermore, genetic studies and biochemical analysis show that Step interacts with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK activation.

  17. Cardiotoxin III Inhibits Proliferation and Migration of Oral Cancer Cells through MAPK and MMP Signaling

    Directory of Open Access Journals (Sweden)

    Ching-Yu Yen

    2013-01-01

    Full Text Available Cardiotoxin III (CTXIII, isolated from the snake venom of Formosan cobra Naja naja atra, has previously been found to induce apoptosis in many types of cancer. Early metastasis is typical for the progression of oral cancer. To modulate the cell migration behavior of oral cancer is one of the oral cancer therapies. In this study, the possible modulating effect of CTXIII on oral cancer migration is addressed. In the example of oral squamous carcinoma Ca9-22 cells, the cell viability was decreased by CTXIII treatment in a dose-responsive manner. In wound-healing assay, the cell migration of Ca9-22 cells was attenuated by CTXIII in a dose- and time-responsive manner. After CTXIII treatment, the MMP-2 and MMP-9 protein expressions were downregulated, and the phosphorylation of JNK and p38-MAPK was increased independent of ERK phosphorylation. In conclusion, CTXIII has antiproliferative and -migrating effects on oral cancer cells involving the p38-MAPK and MMP-2/-9 pathways.

  18. Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

    Science.gov (United States)

    Gao, Tingting; Zhao, Xin; Liu, Chenchen; Shao, Binbin; Zhang, Xi; Li, Kai; Cai, Jinyang; Wang, Su; Huang, Xiaoyan

    2018-05-24

    Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. KEGG pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and cell cycle. sACE was found to play an important role in SSC self-renewal via the regulation of MAPK-dependent cell proliferation.

  19. A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites

    DEFF Research Database (Denmark)

    Dang, Pham My-Chan; Stensballe, Allan; Boussetta, Tarek

    2006-01-01

    mass spectrometry to show that GM-CSF and TNF-alpha induce phosphorylation of Ser345 on p47phox, a cytosolic component of NADPH oxidase, in human neutrophils. As Ser345 is located in the MAPK consensus sequence, we tested the effects of MAPK inhibitors. Inhibitors of the ERK1/2 pathway abrogated GM......Neutrophil NADPH oxidase plays a key role in host defense and in inflammation by releasing large amounts of superoxide and other ROSs. Proinflammatory cytokines such as GM-CSF and TNF-alpha prime ROS production by neutrophils through unknown mechanisms. Here we used peptide sequencing by tandem...

  20. Identification of Biokinetic Models Using the Concept of Extents.

    Science.gov (United States)

    Mašić, Alma; Srinivasan, Sriniketh; Billeter, Julien; Bonvin, Dominique; Villez, Kris

    2017-07-05

    The development of a wide array of process technologies to enable the shift from conventional biological wastewater treatment processes to resource recovery systems is matched by an increasing demand for predictive capabilities. Mathematical models are excellent tools to meet this demand. However, obtaining reliable and fit-for-purpose models remains a cumbersome task due to the inherent complexity of biological wastewater treatment processes. In this work, we present a first study in the context of environmental biotechnology that adopts and explores the use of extents as a way to simplify and streamline the dynamic process modeling task. In addition, the extent-based modeling strategy is enhanced by optimal accounting for nonlinear algebraic equilibria and nonlinear measurement equations. Finally, a thorough discussion of our results explains the benefits of extent-based modeling and its potential to turn environmental process modeling into a highly automated task.

  1. Extent, accuracy, and credibility of breastfeeding information on the Internet.

    Science.gov (United States)

    Shaikh, Ulfat; Scott, Barbara J

    2005-05-01

    Our objective was to test and describe a model for evaluating Websites related to breastfeeding. Forty Websites most likely to be accessed by the public were evaluated for extent, accuracy, credibility, presentation, ease of use, and adherence to ethical and medical Internet publishing standards. Extent and accuracy of Website content were determined by a checklist of critical information. The majority of Websites reviewed provided accurate information and complied with the International Code of Marketing of Breast-milk Substitutes. Approximately half the Websites complied with standards of medical Internet publishing. While much information on breastfeeding on the Internet is accurate, there is wide variability in the extent of information, usability of Websites, and compliance with standards of medical Internet publishing. Results of this study may be helpful to health care professionals as a model for evaluating breastfeeding-related Websites and to highlight considerations when recommending or designing Websites.

  2. Real-time flood extent maps based on social media

    Science.gov (United States)

    Eilander, Dirk; van Loenen, Arnejan; Roskam, Ruud; Wagemaker, Jurjen

    2015-04-01

    During a flood event it is often difficult to get accurate information about the flood extent and the people affected. This information is very important for disaster risk reduction management and crisis relief organizations. In the post flood phase, information about the flood extent is needed for damage estimation and calibrating hydrodynamic models. Currently, flood extent maps are derived from a few sources such as satellite images, areal images and post-flooding flood marks. However, getting accurate real-time or maximum flood extent maps remains difficult. With the rise of social media, we now have a new source of information with large numbers of observations. In the city of Jakarta, Indonesia, the intensity of unique flood related tweets during a flood event, peaked at 8 tweets per second during floods in early 2014. A fair amount of these tweets also contains observations of water depth and location. Our hypothesis is that based on the large numbers of tweets it is possible to generate real-time flood extent maps. In this study we use tweets from the city of Jakarta, Indonesia, to generate these flood extent maps. The data-mining procedure looks for tweets with a mention of 'banjir', the Bahasa Indonesia word for flood. It then removes modified and retweeted messages in order to keep unique tweets only. Since tweets are not always sent directly from the location of observation, the geotag in the tweets is unreliable. We therefore extract location information using mentions of names of neighborhoods and points of interest. Finally, where encountered, a mention of a length measure is extracted as water depth. These tweets containing a location reference and a water level are considered to be flood observations. The strength of this method is that it can easily be extended to other regions and languages. Based on the intensity of tweets in Jakarta during a flood event we can provide a rough estimate of the flood extent. To provide more accurate flood extend

  3. Interactive effects between nest microclimate and nest vegetation structure confirm microclimate thresholds for Lesser Prairie-Chicken nest survival

    Science.gov (United States)

    Grisham, Blake A.; Godar, Alixandra J.; Boal, Clint W.; Haukos, David A.

    2016-01-01

    The range of Lesser Prairie-Chickens (Tympanuchus pallidicinctus) spans 4 unique ecoregions along 2 distinct environmental gradients. The Sand Shinnery Oak Prairie ecoregion of the Southern High Plains of New Mexico and Texas is environmentally isolated, warmer, and more arid than the Short-Grass, Sand Sagebrush, and Mixed-Grass Prairie ecoregions in Colorado, Kansas, Oklahoma, and the northeast panhandle of Texas. Weather is known to influence Lesser Prairie-Chicken nest survival in the Sand Shinnery Oak Prairie ecoregion; regional variation may also influence nest microclimate and, ultimately, survival during incubation. To address this question, we placed data loggers adjacent to nests during incubation to quantify temperature and humidity distribution functions in 3 ecoregions. We developed a suite of a priori nest survival models that incorporated derived microclimate parameters and visual obstruction as covariates in Program MARK. We monitored 49 nests in Mixed-Grass, 22 nests in Sand Shinnery Oak, and 30 nests in Short-Grass ecoregions from 2010 to 2014. Our findings indicated that (1) the Sand Shinnery Oak Prairie ecoregion was hotter and drier during incubation than the Mixed- and Short-Grass ecoregions; (2) nest microclimate varied among years within ecoregions; (3) visual obstruction was positively associated with nest survival; but (4) daily nest survival probability decreased by 10% every half-hour when temperature was greater than 34°C and vapor pressure deficit was less than −23 mmHg during the day (about 0600–2100 hours). Our major finding confirmed microclimate thresholds for nest survival under natural conditions across the species' distribution, although Lesser Prairie-Chickens are more likely to experience microclimate conditions that result in nest failures in the Sand Shinnery Oak Prairie ecoregion. The species would benefit from identification of thermal landscapes and management actions that promote cooler, more humid nest microclimates.

  4. Modified Mitchell osteotomy alone does not have higher rate of residual metatarsalgia than combined first and lesser metatarsal osteotomy

    Directory of Open Access Journals (Sweden)

    Shu-Jung Chen

    2015-04-01

    Full Text Available Transfer metatarsalgia (TM is a common forefoot disorder secondary to hallux valgus (HV. Some authors suggest that a combined lesser metatarsal osteotomy while undergoing HV surgery improves metatarsalgia, whereas others concluded that isolated HV corrective osteotomy can improve symptomatic metatarsalgia. The main purpose of this retrospective study was to compare clinical outcomes in patients with and without combined lesser metatarsal osteotomy while receiving HV correction surgery. We retrospectively reviewed the patients who underwent osteotomy for HV correction between January 2000 and December 2010. All patients underwent HV correction with modified Mitchell osteotomy. Clinical evaluations including the American Orthopaedic Foot and Ankle Society score and residual metatarsalgia were assessed, and radiographic measurements were carried out. Sixty-five patients (83 feet meeting the selection criteria were enrolled. Thirty feet receiving a combined lesser metatarsal osteotomy were classified as the combined surgery (CS group, and the others were classified as the control (CN group (53 feet. The overall rate of persistent symptomatic metatarsalgia was 19.28% after operative treatment. There were six feet with residual metatarsalgia in the CS group, and 10 feet in the CN group. There was no significant difference in the rate of persistent symptoms between the two groups (p = 0.9. According to this result, modified Mitchell osteotomy alone did not have a higher rate of residual metatarsalgia than CS. We also found that the average recovery rate of TM was about 80.7% and those patients whose preoperative HV angle was > 30° had the higher risk of residual metatarsalgia after surgery.

  5. LEVEL AND EXTENT OF MERCURY CONTAMINATION IN OREGON LOTIC FISH

    Science.gov (United States)

    As part of the U.S. EPA's EMAP Oregon Pilot project, we conducted a probability survey of 154 Oregon streams and rivers to assess the spatial extent of mercury (Hg) contamination in fish tissue across the state. Samples consisted of whole fish analyses of both small (< 120 mm) a...

  6. Spatial extent in demographic research - approach and problems

    Directory of Open Access Journals (Sweden)

    Knežević Aleksandar

    2015-01-01

    Full Text Available One of the starting methodological problems in demographic research is the definition of spatial extent, which mostly doesn’t correspond to spatial extent already defined by different levels of administrative-territorial unitsthat are used for distribution of usable statistical data. That’s why determining the spatial extent of a demographic research is closely tied with administrative-territorial division of the territory that is being researched, wherein the fact that differentiation of demographic phenomena and processes cannot be the only basis of setting the principles of regionalization must be strictly acknowledged. This problem is particularly common in historical demographic analyses of geographically determined wholes, which are in administratively-territorial sense represented by one or more smaller territorial units, with their borders changing through the history, which directly affects comparability of the statistical data, and makes it considerably more difficult to track demographic change through longer time intervals. The result of these efforts is usually a solution based on a compromise which enables us to examine the dynamics of population change with little deviation from already defined borders of regional geographic wholes. For that reason in this paper the problem of defining spatial extent in demographic research is examined trough several different approaches in case of Eastern Serbia, as a geographically determined region, a historic area, a spatially functioning whole and as a statistical unit for demographic research, with no judgment calls in regard to any of the regionalization principles. [Projekat Ministarstva nauke Republike Srbije, br. III 47006

  7. The Extent of Immature Fish Harvesting by the Commercial Fishery ...

    African Journals Online (AJOL)

    The sustainability of a given fishery is a function of the number of sexually matured fish present in water. If there is intensive immature fishing, the population of fish reaching the stage of recruitment will decrease, which in turn results in lower yield and biomass. The present study was conducted to estimate the extent of ...

  8. Does Trust Influence the Extent of Inter-Organizational Barter?

    DEFF Research Database (Denmark)

    Sudzina, Frantisek

    2014-01-01

    The 1999 World Business Environment Survey investigated, among many other things, the extent of inter-organizational barter in various countries. Reported values differed a lot, e.g. it was less than 1% in Hungary but more than 30% in neighboring Croatia. Since in many such contracts goods and...

  9. Veterinary drug prescriptions: to what extent do pet owners comply ...

    African Journals Online (AJOL)

    Separate questionnaires were designed for pet owners (clients) and veterinarians to ascertain the existence and extent of noncompliance in veterinary practice in lbadan and to elucidate the influence of such factors as logistics, education, economy, attitudes and veterinarian/client relationship on non-compliance. Analyses ...

  10. To what extent does banks' credit stimulate economic growth ...

    African Journals Online (AJOL)

    This study examines the extent to which banks' credit affects economic growth in Nigeria. The data used was collected from the Central Bank of Nigeria statistical bulletin for a period of 24 years from 1990 to 2013. We used credit to the private sector, credit to the public sector and inflation to proxy commercial bank credit ...

  11. Extent of reaction in open systems with multiple heterogeneous reactions

    Science.gov (United States)

    Friedly, John C.

    1991-01-01

    The familiar batch concept of extent of reaction is reexamined for systems of reactions occurring in open systems. Because species concentrations change as a result of transport processes as well as reactions in open systems, the extent of reaction has been less useful in practice in these applications. It is shown that by defining the extent of the equivalent batch reaction and a second contribution to the extent of reaction due to the transport processes, it is possible to treat the description of the dynamics of flow through porous media accompanied by many chemical reactions in a uniform, concise manner. This approach tends to isolate the reaction terms among themselves and away from the model partial differential equations, thereby enabling treatment of large problems involving both equilibrium and kinetically controlled reactions. Implications on the number of coupled partial differential equations necessary to be solved and on numerical algorithms for solving such problems are discussed. Examples provided illustrate the theory applied to solute transport in groundwater flow.

  12. Extent and Distribution of Groundwater Resources in Parts of ...

    African Journals Online (AJOL)

    The extent and distribution of groundwater resources in parts of Anambra State, Nigeria has been investigated. The results show that the study area is directly underlain by four different geological formations including, Alluvial Plain Sands, Ogwashi-Asaba Formation, Ameki/Nanka Sands and Imo Shale, with varying water ...

  13. Extent of implementation of collection development policies in ...

    African Journals Online (AJOL)

    The study is a survey research on the extent of implementation of collection development policies in academic libraries in Imo state. The population of the study comprises five (5) academic libraries in the area of study. The academic libraries understudy are: Imo State University Owerri (IMSU), Federal University of ...

  14. An investigation into Nigerian teacher's attitude towards and extent ...

    African Journals Online (AJOL)

    The attitude of Biology teachers towards and their extent of improvisation, were investigated 80 teachers from 50 randomly selected secondary schools in Oyo state of Nigeria participated in the study. Analysis of the twenty item questionnaire administered to the teachers revealed that though many of them exhibited positive ...

  15. Extent of implementation of Collection Development Policies (CDP ...

    African Journals Online (AJOL)

    The study was on the extent of implementation of collection development policies by public University libraries in the Niger Delta Area, Nigeria. Descriptive survey design was employed. Population for the study consisted of all the 16 Colle ction Development Librarians in the Area studied. No sample was used because the ...

  16. The extent of groundwater use for domestic and irrigation activities ...

    African Journals Online (AJOL)

    AKMENSAH

    2015-06-04

    Jun 4, 2015 ... Albert Kobina Mensah1*, Evans Appiah Kissi2, Kwabena Krah3 and Okoree D. Mireku4. 1Department of Geography, Kenyatta University, Nairobi. 2Department of .... catchment in Kiambu County in Kenya had limited themselves to the assessment of water quality. Little work has been done on the extent to ...

  17. Forest extent and deforestation in tropical Africa since 1900.

    Science.gov (United States)

    Aleman, Julie C; Jarzyna, Marta A; Staver, A Carla

    2018-01-01

    Accurate estimates of historical forest extent and associated deforestation rates are crucial for quantifying tropical carbon cycles and formulating conservation policy. In Africa, data-driven estimates of historical closed-canopy forest extent and deforestation at the continental scale are lacking, and existing modelled estimates diverge substantially. Here, we synthesize available palaeo-proxies and historical maps to reconstruct forest extent in tropical Africa around 1900, when European colonization accelerated markedly, and compare these historical estimates with modern forest extent to estimate deforestation. We find that forests were less extensive in 1900 than bioclimatic models predict. Resultantly, across tropical Africa, ~ 21.7% of forests have been deforested, yielding substantially slower deforestation than previous estimates (35-55%). However, deforestation was heterogeneous: West and East African forests have undergone almost complete decline (~ 83.3 and 93.0%, respectively), while Central African forests have expanded at the expense of savannahs (~ 1.4% net forest expansion, with ~ 135,270 km 2 of savannahs encroached). These results suggest that climate alone does not determine savannah and forest distributions and that many savannahs hitherto considered to be degraded forests are instead relatively old. These data-driven reconstructions of historical biome distributions will inform tropical carbon cycle estimates, carbon mitigation initiatives and conservation planning in both forest and savannah systems.

  18. The Extent of Reversibility of Polychlorinated Biphenyl Adsorption

    Science.gov (United States)

    The extent of reversibility of PCB bonding to sediments has been characterized in studies on the partitioning behavior of a hexachlorobiphenyl isomer. Linear non-singular isotherms have been observed for the adsorption and desorption of 2.4.5.2?,4?,5? hexachlorobiphenyl (HCBP) to...

  19. The Extent of Educational Technology's Influence on Contemporary Educational Practices

    OpenAIRE

    Kim, Bradford-Watts

    2005-01-01

    This paper investigates how advances in educational technologies have influenced contemporary educational practices.It discusses the nature of educational technology, the limitations imposed by the digital divide and other factors of uptake, and the factors leading to successful implementation of educational technologies.The extent of influence is then discussed,together with the probable implications for educational sites for the future.

  20. Determining wetland spatial extent and seasonal variations of the ...

    African Journals Online (AJOL)

    This study, done in the Witbank Dam Catchment in Mpumalanga Province of South Africa, explores a remote-sensing technique to delineate wetland extent and assesses the seasonal variations of the inundated area. The objective was to monitor the spatio-temporal changes of wetlands over time through remote sensing ...

  1. 32 CFR 728.12 - Extent of care.

    Science.gov (United States)

    2010-07-01

    ... § 728.12 Extent of care. Members who are away from their duty stations or are on duty where there is no... providing authorization for non-Federal care at DHHS expense. (b) Maternity episode for active duty female... facilities (once the mother has been admitted to the USMTF) from funds available for care of active duty...

  2. 27 CFR 24.158 - Extent of relief.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Extent of relief. 24.158 Section 24.158 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT..., until all tax is fully paid. (d) Wine vinegar plant bond. The surety will be relieved of liability for...

  3. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    International Nuclear Information System (INIS)

    Mishra, Sakshi; Tripathi, Anurag; Chaudhari, Bhushan P.; Dwivedi, Premendra D.; Pandey, Haushila P.; Das, Mukul

    2014-01-01

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [ 3 H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF

  4. Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK.

    Science.gov (United States)

    Witting Christensen, S K; Kortekaas Krohn, I; Thuraiaiyah, J; Skjold, T; Schmid, J M; Hoffmann, H J H

    2014-10-01

    Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10). Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Effects of andrographolide on postoperative cognitive dysfunction and the association with NF-κB/MAPK pathway.

    Science.gov (United States)

    Ding, Yongbo; Shi, Cunxian; Chen, Linjing; Ma, Piliang; Li, Kezhong; Jin, Jin; Zhang, Qingfeng; Li, Aizhi

    2017-12-01

    The present study investigated the effects of andrographolide on postoperative cognitive dysfunction (POCD) in aged rats to gain insight of the underlying mechanism, which may provide theoretical basis for the clinical application of andrographolide to prevent POCD in older patients. Thirty aged male rats were randomly assigned to 3 groups: Control, model and andrographolide groups. The Morris water maze test was used to examine the spatial memory and learning ability of the rats postoperatively. The histological alterations of neuronal cells in the hippocampus were visualized by H&E staining. The serum levels of neuron-specific enolase (NSE), human soluble protein-100β (S-100β) and the inflammation factors of interluekin (IL)-1β, IL-6 and TNF-α involved in the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway were detected by ELISA. The NF-κB/MAPK signaling pathway-associated proteins in rat serum were detected by western blotting. Following andrographolide treatment, the rats significantly gained learning ability after surgery. Is it ameliorated hippocampal neuronal injury in rats following surgery. Andrographolide decreased NSE, S-100β, and the inflammation factors, IL-6, IL-1β and TNF-α in serum. Andrographolide reduced NF-κB/MAPK pathway-associated protein expression. Andrographolide ameliorated POCD in aged rats following surgery. The underlying mechanism may be associated with the downregulation the inflammatory factors and NF-κB/MAPK-associated protein expression.

  6. Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-κB pathways.

    Science.gov (United States)

    Zhang, Lai-Bo; Man, Zhen-Tao; Li, Wei; Zhang, Wei; Wang, Xian-Quan; Sun, Shui

    2017-07-01

    Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of osteoporosis. However, little information is available about the effects of CT on osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on the treatment of OA, as well as the underlying mechanisms. Chondrocytes were isolated from immature mice and then were incubated with lipopolysaccharide (LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2, and/or the inhibitors of MAPK/Wnt/NF-κB pathway. Thereafter, cell viability, apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression levels of cartilage synthesis protein key factors, cartilage-derived morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein (SOX9), and MAPK/Wnt/NF-κB pathways key factors were determined. CT significantly reversed LPS-induced cell viability decrease, apoptosis increase, the inflammatory factors and NO secretion, the abnormally expression of cartilage synthesis proteins and the activation of MAPK/Wnt/NF-κB pathways (Ppathways statistically further increased the levels of CDMP1 and SOX9 (Ppathways, and could partially abolish CT-modulated the expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-κB pathways key factors (Ppathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients.

    Science.gov (United States)

    Luo, Lin; Zhou, Wen-Hua; Cai, Jiang-Jia; Feng, Mei; Zhou, Mi; Hu, Su-Pei; Xu, Jin; Ji, Lin-Dan

    2017-01-01

    Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the "neurotrophin-MAPK signaling pathway" was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

  8. Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

    KAUST Repository

    Frei dit Frey, Nicolas; Garcia, Ana; Bigeard, Jean; Zaag, Rim; Bueso, Eduardo; Garmier, Marie; Pateyron, Sté phanie; de Tauzia-Moreau, Marie-Ludivine; Brunaud, Vé ronique; Balzergue, Sandrine; Colcombet, Jean; Aubourg, Sé bastien; Martin-Magniette, Marie-Laure; Hirt, Heribert

    2014-01-01

    -induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76

  9. p38 MAPK plays an essential role in apoptosis induced by photoactivation of a novel ethylene glycol porphyrin derivative

    Czech Academy of Sciences Publication Activity Database

    Králová, Jarmila; Dvořák, Michal; Koc, Michal; Král, V.

    2008-01-01

    Roč. 27, č. 21 (2008), s. 3010-3020 ISSN 0950-9232 R&D Projects: GA AV ČR KAN200200651 Institutional research plan: CEZ:AV0Z50520514 Keywords : porphyrin * photoactivation * apoptosis of tumour cells * p38 MAPK, caspase * lysosome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.216, year: 2008

  10. p38 MAPK pathway is essential for self-renewal of mouse male germline stem cells (mGSCs).

    Science.gov (United States)

    Niu, Zhiwei; Mu, Hailong; Zhu, Haijing; Wu, Jiang; Hua, Jinlian

    2017-02-01

    Male germline stem cells (mGSCs), also called spermatogonial stem cells (SSCs), constantly generate spermatozoa in male animals. A number of preliminary studies on mechanisms of mGSC self-renewal have previously been conducted, revealing that several factors are involved in this regulated process. The p38 MAPK pathway is widely conserved in multiple cell types in vivo, and plays an important role in cell proliferation, differentiation, inflammation and apoptosis. However, its role in self-renewal of mGSCs has not hitherto been determined. Here, the mouse mGSCs were cultured and their identity was verified by semi-RT-PCR, alkaline phosphatase (AP) staining and immunofluorescence staining. Then, the p38 MAPK pathway was blocked by p38 MAPK-specific inhibitor SB202190. mGSC self-renewal ability was then analysed by observation of morphology, cell number, cell growth analysis, TUNEL incorporation assay and cell cycle analysis. Results showed that mouse mGSC self-renewal ability was significantly inhibited by SB202190. This study showed for the first time that the p38 MAPK pathway plays a key role in maintaining self-renewal capacity of mouse mGSCs, which offers a new self-renewal pathway for these cells and contributes to overall knowledge of the mechanisms of mGSC self-renewal. © 2016 John Wiley & Sons Ltd.

  11. Differential Roles of Grb2 and AP-2 in p38 MAPK- and EGF-Induced EGFR Internalization

    DEFF Research Database (Denmark)

    Grandal, Michael V; Grøvdal, Lene M; Henriksen, Lasse

    2012-01-01

    The epidermal growth factor receptor (EGFR) is an important regulator of normal growth and differentiation, and it is involved in the pathogenesis of many cancers. Endocytic downregulation is central in terminating EGFR signaling after ligand stimulation. It has been shown that p38 MAPK activation...

  12. Reduced Drought Tolerance by CRISPR/Cas9-Mediated SlMAPK3 Mutagenesis in Tomato Plants.

    Science.gov (United States)

    Wang, Liu; Chen, Lin; Li, Rui; Zhao, Ruirui; Yang, Meijing; Sheng, Jiping; Shen, Lin

    2017-10-04

    Drought stress is one of the most destructive environmental factors that affect tomato plants adversely. Mitogen-activated protein kinases (MAPKs) are important signaling molecules that respond to drought stress. In this study, SlMAPK3 was induced by drought stress, and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system was utilized to generate slmapk3 mutants. Two independent T1 transgenic lines and wild-type (WT) tomato plants were used for analysis of drought tolerance. Compared with WT plants, slmapk3 mutants exhibited more severe wilting symptom, higher hydrogen peroxide content, lower antioxidant enzymes activities, and suffered more membrane damage under drought stress. Furthermore, knockout of SlMAPK3 led to up- or down-regulated expressions of drought stress-responsive genes including SlLOX, SlGST, and SlDREB. The results suggest that SlMAPK3 is involved in drought response in tomato plants by protecting cell membranes from oxidative damage and modulating transcription of stress-related genes.

  13. Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

    International Nuclear Information System (INIS)

    Wu, Hai-Lu; Gao, Xin; Jiang, Zong-Dan; Duan, Zhao-Tao; Wang, Shu-Kui; He, Bang-Shun; Zhang, Zhen-Yu; Xie, Hong-Guang

    2013-01-01

    Highlights: ► Clopidogrel suppressed GES-1 cell viability in a concentration- and time-dependent manner. ► Clopidogrel significantly increased dextran permeability, reduced occludin and ZO-1 expression, and induced cell apoptosis. ► Clopidogrel activated p38 MAPK signaling pathway. ► Activation of p38 activity was involved in clopidogrel-induced increase in gastric epithelial cells permeability and disruption of TJ. -- Abstract: Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5–2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric

  14. Nicotiana benthamiana MAPK-WRKY pathway confers resistance to a necrotrophic pathogen Botrytis cinerea.

    Science.gov (United States)

    Adachi, Hiroaki; Ishihama, Nobuaki; Nakano, Takaaki; Yoshioka, Miki; Yoshioka, Hirofumi

    2016-06-02

    MEK2-SIPK/WIPK cascade, a Nicotiana benthamiana mitogen-activated protein kinase (MAPK) cascade, is an essential signaling pathway for plant immunity and involved in hypersensitive response (HR) accompanied by cell death. WRKY transcription factors as substrates of SIPK and WIPK have been isolated and implicated in HR cell death. Here, we show virus-induced gene silencing of WRKY genes compromised constitutively active MEK2-triggered cell death in N. benthamiana leaves. In general, HR cell death enhances susceptibility to necrotrophic pathogens such as Botrytis cinerea. However, the WRKY gene silencing elevated susceptibility to B. cinerea. These findings suggest that downstream WRKYs of MEK2-SIPK/WIPK cascade are required for cell death-dependent and -independent immunities in N. benthamiana.

  15. An algorithm for modularization of MAPK and calcium signaling pathways: comparative analysis among different species.

    Science.gov (United States)

    Nayak, Losiana; De, Rajat K

    2007-12-01

    Signaling pathways are large complex biochemical networks. It is difficult to analyze the underlying mechanism of such networks as a whole. In the present article, we have proposed an algorithm for modularization of signal transduction pathways. Unlike studying a signaling pathway as a whole, this enables one to study the individual modules (less complex smaller units) easily and hence to study the entire pathway better. A comparative study of modules belonging to different species (for the same signaling pathway) has been made, which gives an overall idea about development of the signaling pathways over the taken set of species of calcium and MAPK signaling pathways. The superior performance, in terms of biological significance, of the proposed algorithm over an existing community finding algorithm of Newman [Newman MEJ. Modularity and community structure in networks. Proc Natl Acad Sci USA 2006;103(23):8577-82] has been demonstrated using the aforesaid pathways of H. sapiens.

  16. Salidroside protects against foam cell formation and apoptosis, possibly via the MAPK and AKT signaling pathways.

    Science.gov (United States)

    Ni, Jing; Li, Yuanmin; Li, Weiming; Guo, Rong

    2017-10-10

    Foam cell formation and apoptosis are closely associated with atherosclerosis pathogenesis. We determined the effect of salidroside on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation and apoptosis in THP1 human acute monocytic leukemia cells and investigated the associated molecular mechanisms. THP1-derived macrophages were incubated with salidroside for 5 h and then exposed to ox-LDL for 24 h to induce foam cell formation. Cytotoxicity, lipid deposition, apoptosis, and the expression of various proteins were tested using the CCK8 kit, Oil Red O staining, flow cytometry, and western blotting, respectively. Ox-LDL treatment alone promoted macrophage-derived foam cell formation, while salidroside treatment alone inhibited it (p foam cell formation and apoptosis, partly by regulating the MAPK and Akt signaling pathways.

  17. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate...... agonist, Sarafotoxin 6c (S6c) caused a time-dependent ERK1/2 activation with a maximal effect by less than 20% of the ET-1-induced activation of ERK1/2. Increase in bosentan concentration up to 10 microM further inhibited ET-1-induced activation of ERK1/2 and had a stronger inhibitory effect than BQ123...

  18. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Jiamin [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Yang, Jianbing [Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001 (China); Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wang, Cheng [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Nie, Xiaoke [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Chen, Gang, E-mail: chengang@ntu.edu.cn [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

    2016-07-15

    Arsenic is a widely distributed toxic metalloid all over the world. Inorganic arsenic species are supposed to affect astrocytic functions and to cause neuron apoptosis in CNS. Microglias are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA, we showed that Arsenic trioxide up-regulated the expression and secretion of IL-1β in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. The secretion of IL-1β caused the apoptosis of SH-SY5Y. These pro-inflammatory responses were inhibited by the STAT3 blocker, AG490 and P38/JNK MAPK blockers SB202190, SP600125. Further, Arsenic trioxide exposure could induce phosphorylation and activation of STAT3, and the translocation of STAT3 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the STAT3 signaling pathway can be activated after Arsenic trioxide treatment. However, P38/JNK MAPK blockers SB202190, SP600125 also obviously attenuated STAT3 activation and transnuclear transport induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. - Highlights: • Arsenic trioxide exposure induced expression of IL-β in HAPI microglia. • Arsenic trioxide exposure induced activation of MAPK pathways in HAPI microglia. • Arsenic trioxide exposure induced activation of STAT3 pathways in HAPI microglia. • The expression of IL-β though P38/JNK MAPK/STAT3 pathways in HAPI microglia.

  19. Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model

    Science.gov (United States)

    Liu, Wei; Jiang, Hong-li; Cai, Lin-li; Yan, Min; Dong, Shou-jin; Mao, Bing

    2016-01-01

    Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1β, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/β, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1β, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/β, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner. PMID:27366191

  20. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

    International Nuclear Information System (INIS)

    Wang, Cheng; Nie, Xiaoke; Zhang, Yan; Li, Ting; Mao, Jiamin; Liu, Xinhang; Gu, Yiyang; Shi, Jiyun; Xiao, Jing; Wan, Chunhua; Wu, Qiyun

    2015-01-01

    Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

  1. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng; Nie, Xiaoke; Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting; Mao, Jiamin [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Liu, Xinhang [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Gu, Yiyang; Shi, Jiyun [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xiao, Jing [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wu, Qiyun, E-mail: wqy@ntu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

    2015-10-15

    Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

  2. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway

    International Nuclear Information System (INIS)

    Mao, Jiamin; Yang, Jianbing; Zhang, Yan; Li, Ting; Wang, Cheng; Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang; Nie, Xiaoke; Chen, Gang

    2016-01-01

    Arsenic is a widely distributed toxic metalloid all over the world. Inorganic arsenic species are supposed to affect astrocytic functions and to cause neuron apoptosis in CNS. Microglias are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA, we showed that Arsenic trioxide up-regulated the expression and secretion of IL-1β in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. The secretion of IL-1β caused the apoptosis of SH-SY5Y. These pro-inflammatory responses were inhibited by the STAT3 blocker, AG490 and P38/JNK MAPK blockers SB202190, SP600125. Further, Arsenic trioxide exposure could induce phosphorylation and activation of STAT3, and the translocation of STAT3 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the STAT3 signaling pathway can be activated after Arsenic trioxide treatment. However, P38/JNK MAPK blockers SB202190, SP600125 also obviously attenuated STAT3 activation and transnuclear transport induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. - Highlights: • Arsenic trioxide exposure induced expression of IL-β in HAPI microglia. • Arsenic trioxide exposure induced activation of MAPK pathways in HAPI microglia. • Arsenic trioxide exposure induced activation of STAT3 pathways in HAPI microglia. • The expression of IL-β though P38/JNK MAPK/STAT3 pathways in HAPI microglia.

  3. Missense Variant in MAPK Inactivator PTPN5 Is Associated with Decreased Severity of Post-Burn Hypertrophic Scarring.

    Directory of Open Access Journals (Sweden)

    Ravi F Sood

    Full Text Available Hypertrophic scarring (HTS is hypothesized to have a genetic mechanism, yet its genetic determinants are largely unknown. The mitogen-activated protein kinase (MAPK pathways are important mediators of inflammatory signaling, and experimental evidence implicates MAPKs in HTS formation. We hypothesized that single-nucleotide polymorphisms (SNPs in MAPK-pathway genes would be associated with severity of post-burn HTS.We analyzed data from a prospective-cohort genome-wide association study of post-burn HTS. We included subjects with deep-partial-thickness burns admitted to our center who provided blood for genotyping and had at least one Vancouver Scar Scale (VSS assessment. After adjusting for HTS risk factors and population stratification, we tested MAPK-pathway gene SNPs for association with the four VSS variables in a joint regression model. In addition to individual-SNP analysis, we performed gene-based association testing.Our study population consisted of 538 adults (median age 40 years who were predominantly White (76% males (71% admitted to our center from 2007-2014 with small-to-moderate-sized burns (median burn size 6% total body surface area. Of 2,146 SNPs tested, a rare missense variant in the PTPN5 gene (rs56234898; minor allele frequency 1.5% was significantly associated with decreased severity of post-burn HTS (P = 1.3×10-6. In gene-based analysis, PTPN5 (P = 1.2×10-5 showed a significant association and BDNF (P = 9.5×10-4 a borderline-significant association with HTS severity.We report PTPN5 as a novel genetic locus associated with HTS severity. PTPN5 is a MAPK inhibitor expressed in neurons, suggesting a potential role for neurotrophic factors and neuroinflammatory signaling in HTS pathophysiology.

  4. Immunosuppressant MPA Modulates Tight Junction through Epigenetic Activation of MLCK/MLC-2 Pathway via p38MAPK

    Directory of Open Access Journals (Sweden)

    Niamat Khan

    2015-12-01

    Full Text Available Background: Mycophenolic acid (MPA is an important immunosuppressive drug (ISD prescribed to prevent graft rejection in the organ transplanted patients, however, its use is also associated with adverse side effects like sporadic gastrointestinal (GI disturbances. Recently, we reported the MPA induced tight junctions (TJs deregulation which involves MLCK/MLC-2 pathway. Here, we investigated the global histone acetylation as well as gene-specific chromatin signature of several genes associated with TJs regulation in Caco-2 cells after MPA treatment.Results: The epigenetic analysis shows that MPA treatment increases the global histone acetylation levels as well as the enrichment for transcriptional active histone modification mark (H3K4me3 at promoter regions of p38MAPK, ATF-2, MLCK, and MLC-2. In contrast, the promoter region of occludin was enriched for transcriptional repressive histone modification mark (H3K27me3 after MPA treatment. In line with the chromatin status, MPA treatment increased the expression of p38MAPK, ATF-2, MLCK, and MLC-2 both at transcriptional and translational level, while occludin expression was negatively influenced. Interestingly, the MPA induced gene expression changes and functional properties of Caco-2 cells could be blocked by the inhibition of p38MAPK using a chemical inhibitor (SB203580.Conclusions: Collectively, our results highlight that MPA disrupts the structure of TJs via p38MAPK-dependent activation of MLCK/MLC-2 pathway that results in decreased integrity of Caco-2 monolayer. These results led us to suggest that p38MAPK-mediated lose integrity of epithelial monolayer could be the possible cause of GI disturbance (barrier dysfunction in the intestine, leading to leaky style diarrhea observed in the organ-transplanted patients treated with MPA.

  5. Assessing the Global Extent of Rivers Observable by SWOT

    Science.gov (United States)

    Pavelsky, T.; Durand, M. T.; Andreadis, K.; Beighley, E.; Allen, G. H.; Miller, Z.

    2013-12-01

    Flow of water through rivers is among the key fluxes in the global hydrologic cycle and its knowledge would advance the understanding of flood hazards, water resources management, ecology, and climate. However, gauges providing publicly accessible measurements of river stage or discharge remain sparse in many regions. The Surface Water and Ocean Topography (SWOT) satellite mission is a joint project of NASA and the French Centre National d'Etudes Spatiales (CNES) that would provide the first high-resolution images of simultaneous terrestrial water surface height, inundation extent, and ocean surface elevation. Among SWOT's primary goals is the direct observation of variations in river water surface elevation and, where possible, estimation of river discharge from SWOT measurements. The mission science requirements specify that rivers wider than 100 m would be observed globally, with a goal of observing rivers wider than 50m. However, the extent of anticipated SWOT river observations remains fundamentally unknown because no high-resolution, global dataset of river widths exists. Here, we estimate the global extent of rivers wider than 50 m-100 m thresholds using established relationships among river width, discharge, and drainage area. We combine a global digital elevation model with in situ river discharge data to estimate the global extent of SWOT-observable rivers, and validate these estimates against satellite-derived measurements of river width in two large river basins (the Yukon and the Ohio). We then compare the extent of SWOT-observed rivers with the current publicly-available, global gauge network included in the Global Runoff Data Centre (GRDC) database to examine the impact of SWOT on the availability of river observation over continental and global scales. Results suggest that if SWOT observes 100 m wide rivers, river basins with areas greater than 50,000 km2 will commonly be measured. If SWOT could observe 50 m wide rivers, then most 10,000 km2 basins

  6. Smad, but not MAPK, pathway mediates the expression of type I collagen in radiation induced fibrosis

    International Nuclear Information System (INIS)

    Yano, Hiroyuki; Hamanaka, Ryoji; Nakamura, Miki; Sumiyoshi, Hideaki; Matsuo, Noritaka; Yoshioka, Hidekatsu

    2012-01-01

    Highlights: ► We examine how radiation affects the expression level and signal pathway of collagen. ► TGF-β1 mRNA is elevated earlier than those of collagen genes after irradiation. ► Smad pathway mediates the expression of collagen in radiation induced fibrosis. ► MAPK pathways are not affected in the expression of collagen after irradiation. -- Abstract: Radiation induced fibrosis occurs following a therapeutic or accidental radiation exposure in normal tissues. Tissue fibrosis is the excessive accumulation of collagen and other extracellular matrix components. This study investigated how ionizing radiation affects the expression level and signal pathway of type I collagen. Real time RT-RCR showed that both α1and α2 chain of type I collagen mRNA were elevated from 48 h after irradiation with 10 Gy in NIH3T3 cells. The relative luciferase activities of both genes and type I collagen marker were elevated at 72 h. TGF-β1 mRNA was elevated earlier than those of type I collagen genes. A Western blot analysis showed the elevation of Smad phosphorylation at 72 h. Conversely, treatment with TGF-β receptor inhibitor inhibited the mRNA and relative luciferase activity of type I collagen. The phosphorylation of Smad was repressed with the inhibitor, and the luciferase activity was cancelled using a mutant construct of Smad binding site of α2(I) collagen gene. However, the MAPK pathways, p38, ERK1/2 and JNK, were not affected with specific inhibitors or siRNA. The data showed that the Smad pathway mediated the expression of type I collagen in radiation induced fibrosis.

  7. Quantitative cell signalling analysis reveals down-regulation of MAPK pathway activation in colorectal cancer.

    LENUS (Irish Health Repository)

    Gulmann, Christian

    2009-08-01

    Mitogen-activated protein kinases (MAPK) are considered to play significant roles in colonic carcinogenesis and kinase inhibitor therapy has been proposed as a potential tool in the treatment of this disease. Reverse-phase microarray assays using phospho-specific antibodies can directly measure levels of phosphorylated protein isoforms. In the current study, samples from 35 cases of untreated colorectal cancer colectomies were laser capture-microdissected to isolate epithelium and stroma from cancer as well as normal (i.e. uninvolved) mucosa. Lysates generated from these four tissue types were spotted onto reverse-phase protein microarrays and probed with a panel of antibodies to ERK, p-ERK, p38, p-p38, p-JNK, MEK and p-MEK. Whereas total protein levels were unchanged, or slightly elevated (p38, p = 0.0025) in cancers, activated isoforms, including p-ERK, p-p38 and p-JNK, were decreased two- to four-fold in cancers compared with uninvolved mucosa (p < 0.0023 in all cases except for p-JNK in epithelium, where decrement was non-significant). This was backed up by western blotting. Dukes\\' stage B and C cancers displayed lower p-ERK and p-p38 expression than Dukes\\' stage A cancers, although this was not statistically significant. It is concluded that MAPK activity may be down-regulated in colorectal cancer and that further exploration of inhibitory therapy in this system should be carefully evaluated if this finding is confirmed in larger series.

  8. Gold nanoparticles stimulate differentiation and mineralization of primary osteoblasts through the ERK/MAPK signaling pathway

    International Nuclear Information System (INIS)

    Zhang, Dawei; Liu, Dandan; Zhang, Jinchao; Fong, Chichun; Yang, Mengsu

    2014-01-01

    Gold nanoparticles (AuNPs) have shown great promise for a variety of applications, including chemistry, biology, and medicine. Recently, AuNPs have found promising applications in cartilage and bone repair. However, to realize the above promised applications, more work needs to be carried out to clarify the interactions between biological systems and AuNPs. In the present study, primary osteoblasts were used to evaluate the biocompatibility of 20-nm and 40-nm AuNPs, including morphology, proliferation, differentiation, gene and protein expression, and the underlying mechanisms. The results demonstrated that AuNPs were taken up by osteoblasts and aggregated in perinuclear compartment and vescular structures, but no morphological changes were observed. AuNPs could significantly promote the proliferation of osteoblasts, enhance the ALP activities, and increase the number of bone nodules and calcium content in vitro. In addition, the expression of BMP-2, Runx-2, OCN and Col-1 was remarkably up-regulated in the presence of AuNPs. It is noteworthy that 20-nm AuNPs are more potent than 40-nm AuNPs in regulating osteoblast activities. Besides, AuNPs increased the level of ERK phosphorylation/total ERK, suggesting the activation of ERK/MAPK pathway is involved in above activities. In conclusion, AuNPs exhibited great biocompatibility with osteoblasts, and have tremendous potential to be used as drug and/or gene delivery carrier for bone and tissue engineering in the future. - Highlights: • AuNPs aggregated in perinuclear compartment and vescular structures of osteoblasts. • AuNPs up-regulated the expression of Runx-2, BMP-2, OCN and Col I of osteoblasts. • AuNPs enhanced osteoblast differentiation by activating the ERK/MAPK pathway. • The size of nanoparticles may be important to exhibit their biological effects. • AuNPs have tremendous potential in bone and tissue engineering in future

  9. MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium.

    Science.gov (United States)

    Hossen, Muhammad Jahangir; Kim, Mi-Yeon; Cho, Jae Youl

    2016-01-01

    Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

  10. Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations.

    Science.gov (United States)

    Louissaint, Abner; Schafernak, Kristian T; Geyer, Julia T; Kovach, Alexandra E; Ghandi, Mahmoud; Gratzinger, Dita; Roth, Christine G; Paxton, Christian N; Kim, Sunhee; Namgyal, Chungdak; Morin, Ryan; Morgan, Elizabeth A; Neuberg, Donna S; South, Sarah T; Harris, Marian H; Hasserjian, Robert P; Hochberg, Ephraim P; Garraway, Levi A; Harris, Nancy Lee; Weinstock, David M

    2016-08-25

    Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy number analysis and exome and/or targeted sequencing of 26 PTNFLs (16 pediatric and 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22) and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29%, similar to that seen in limited-stage typical FL (P = .35). PTNFL was otherwise genomically bland and specifically lacked recurrent mutations in epigenetic modifiers (eg, CREBBP, KMT2D). Copy number aberrations affected a mean of only 0.5% of PTNFL genomes, compared with 10% of limited-stage typical FL genomes (P < .02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers. © 2016 by The American Society of Hematology.

  11. Smad, but not MAPK, pathway mediates the expression of type I collagen in radiation induced fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Hiroyuki [Department of Matrix Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Division of Radioisotope Research, Department of Research Support, Research Promotion Project, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Hamanaka, Ryoji; Nakamura, Miki [Cell Biology, Faculty of Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Sumiyoshi, Hideaki; Matsuo, Noritaka [Department of Matrix Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan); Yoshioka, Hidekatsu, E-mail: hidey@oita-u.ac.jp [Department of Matrix Medicine, Oita University, 1-1 Idaigaoka Hasama-machi, Yufu, Oita 879-5593 (Japan)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer We examine how radiation affects the expression level and signal pathway of collagen. Black-Right-Pointing-Pointer TGF-{beta}1 mRNA is elevated earlier than those of collagen genes after irradiation. Black-Right-Pointing-Pointer Smad pathway mediates the expression of collagen in radiation induced fibrosis. Black-Right-Pointing-Pointer MAPK pathways are not affected in the expression of collagen after irradiation. -- Abstract: Radiation induced fibrosis occurs following a therapeutic or accidental radiation exposure in normal tissues. Tissue fibrosis is the excessive accumulation of collagen and other extracellular matrix components. This study investigated how ionizing radiation affects the expression level and signal pathway of type I collagen. Real time RT-RCR showed that both {alpha}1and {alpha}2 chain of type I collagen mRNA were elevated from 48 h after irradiation with 10 Gy in NIH3T3 cells. The relative luciferase activities of both genes and type I collagen marker were elevated at 72 h. TGF-{beta}1 mRNA was elevated earlier than those of type I collagen genes. A Western blot analysis showed the elevation of Smad phosphorylation at 72 h. Conversely, treatment with TGF-{beta} receptor inhibitor inhibited the mRNA and relative luciferase activity of type I collagen. The phosphorylation of Smad was repressed with the inhibitor, and the luciferase activity was cancelled using a mutant construct of Smad binding site of {alpha}2(I) collagen gene. However, the MAPK pathways, p38, ERK1/2 and JNK, were not affected with specific inhibitors or siRNA. The data showed that the Smad pathway mediated the expression of type I collagen in radiation induced fibrosis.

  12. Disruption of mitochondrial electron transport chain function potentiates the pro-apoptotic effects of MAPK inhibition.

    Science.gov (United States)

    Trotta, Andrew P; Gelles, Jesse D; Serasinghe, Madhavika N; Loi, Patrick; Arbiser, Jack L; Chipuk, Jerry E

    2017-07-14

    The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma arising from the V600E mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAF V600E ), oncogenic signaling enhances glucose-dependent metabolism while reducing mitochondrial ATP production. Likewise, when BRAF V600E is pharmacologically inhibited by targeted therapies ( e.g. PLX-4032/vemurafenib), glucose metabolism is reduced, and cells increase mitochondrial ATP production to sustain survival. Therefore, collateral inhibition of oncogenic signaling and mitochondrial respiration may help enhance the therapeutic benefit of targeted therapies. Honokiol (HKL) is a well tolerated small molecule that disrupts mitochondrial function; however, its underlying mechanisms and potential utility with targeted anticancer therapies remain unknown. Using wild-type BRAF and BRAF V600E melanoma model systems, we demonstrate here that HKL administration rapidly reduces mitochondrial respiration by broadly inhibiting ETC complexes I, II, and V, resulting in decreased ATP levels. The subsequent energetic crisis induced two cellular responses involving cyclin-dependent kinases (CDKs). First, loss of CDK1-mediated phosphorylation of the mitochondrial division GTPase dynamin-related protein 1 promoted mitochondrial fusion, thus coupling mitochondrial energetic status and morphology. Second, HKL decreased CDK2 activity, leading to G 1 cell cycle arrest. Importantly, although pharmacological inhibition of oncogenic MAPK signaling increased ETC activity, co-treatment with HKL ablated this response and vastly enhanced the rate of apoptosis. Collectively, these findings integrate HKL action with mitochondrial respiration and shape and substantiate a pro-survival role of mitochondrial function in melanoma cells after oncogenic MAPK inhibition.

  13. MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Skye Storrie

    Full Text Available Waddlia chondrophila (W. chondrophila is an emerging agent of respiratory and reproductive disease in humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial agents, such as Chlamydia abortus (C. abortus. The current study investigated the growth characteristics and innate immune responses of human and ruminant epithelial cells in response to infection with W. chondrophila.Human epithelial cells (HEp2 were infected with W. chondrophila for 24h. CXCL8 release was significantly elevated in each of the cell lines by active-infection with live W. chondrophila, but not by exposure to UV-killed organisms. Inhibition of either p38 or p42/44 MAPK significantly inhibited the stimulation of CXCL8 release in each of the cell lines. To determine the pattern recognition receptor through which CXCL8 release was stimulated, wild-type HEK293 cells which express no TLR2, TLR4, NOD2 and only negligible NOD1 were infected with live organisms. A significant increase in CXCL8 was observed.W. chondrophila actively infects and replicates within both human and ruminant epithelial cells stimulating CXCL8 release. Release of CXCL8 is significantly inhibited by inhibition of either p38 or p42/44 MAPK indicating a role for this pathway in the innate immune response to W. chondrophila infection. W. chondrophila stimulation of CXCL8 secretion in HEK293 cells indicates that TLR2, TLR4, NOD2 and NOD1 receptors are not essential to the innate immune response to infection.

  14. Kaempferol Attenuates Cardiac Hypertrophy via Regulation of ASK1/MAPK Signaling Pathway and Oxidative Stress.

    Science.gov (United States)

    Feng, Hong; Cao, Jianlei; Zhang, Guangyu; Wang, Yanggan

    2017-07-01

    Kaempferol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperlipidemia, and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains to be elucidated. The aim of our study was to investigate the effects of kaempferol on cardiac hypertrophy and the underlying mechanism. Mice subjected to aorta banding were treated with or without kaempferol (100 mg/kg/d, p. o.) for 6 weeks. Echocardiography was performed to evaluate cardiac function. Mice hearts were collected for pathological observation and molecular mechanism investigation. H9c2 cardiomyocytes were stimulated with or without phenylephrine for in vitro study. Kaempferol significantly attenuated cardiac hypertrophy induced by aorta banding as evidenced by decreased cardiomyocyte areas and interstitial fibrosis, accompanied with improved cardiac functions and decreased apoptosis. The ASK1/MAPK signaling pathways (JNK1/2 and p38) were markedly activated in the aorta banding mouse heart but inhibited by kaempferol treatment. In in vitro experiments, kaempferol also inhibited the activity of ASK1/JNK1/2/p38 signaling pathway and the enlargement of H9c2 cardiomyocytes. Furthermore, our study revealed that kaempferol could protect the mouse heart and H9c2 cells from pathological oxidative stress. Our investigation indicated that treatment with kaempferol protects against cardiac hypertrophy, and its cardioprotection may be partially explained by the inhibition of the ASK1/MAPK signaling pathway and the regulation of oxidative stress. Georg Thieme Verlag KG Stuttgart · New York.

  15. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif.

    Directory of Open Access Journals (Sweden)

    Mei Ying Ng

    Full Text Available Cycle inhibiting factors (Cifs are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition. This suggests that apart from Nedd8, other cellular targets of Cif-dependent deamidation exist. We provide evidence that the mechanism involved in Cif-mediated ERK activation is dependent on recruitment of the Grb2-SOS1 complex to the plasma membrane. Further investigation revealed that Cif appears to modify the phosphorylation status of SOS1 in a region containing the CDC25-H and proline-rich domains. It is known that prolonged Cullin E3 ligase inhibition leads to cellular apoptosis. Therefore, we hypothesize that ERK activation is an important mechanism to counter the pro-apoptotic effects of Cif. Indeed, we show that Cif dependent ERK activation promotes phosphorylation of the proapoptotic protein Bim, thereby potentially conferring a pro-survival signal. In summary, we identified a novel deamidation-dependent mechanism of action of the B. pseudomallei virulence factor Cif/CHBP to activate MAPK/ERK signaling. Our study demonstrates that bacterial proteins such as Cif can serve as useful molecular tools to uncover novel aspects of mammalian signaling pathways.

  16. ANGPTL3 is a novel biomarker as it activates ERK/MAPK pathway in oral cancer

    International Nuclear Information System (INIS)

    Koyama, Tomoyoshi; Ogawara, Katsunori; Kasamatsu, Atsushi; Okamoto, Atsushi; Kasama, Hiroki; Minakawa, Yasuyuki; Shimada, Ken; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2015-01-01

    Angiopoietin-like 3 (ANGPTL3), which is involved in new blood vessel growth and stimulation of mitogen-activated protein kinase (MAPK), is expressed aberrantly in several types of human cancers. However, little is known about the relevance of ANGPTL3 in the behavior of oral squamous cell carcinoma (OSCC). In this study, we evaluated ANGPTL3 mRNA and protein in OSCC-derived cell lines (n = 8) and primary OSCCs (n = 109) and assessed the effect of ANGPTL3 on the biology and function of OSCCs in vitro and in vivo. Significant (P < 0.05) ANGPTL3 upregulation was detected in the cell lines and most primary OSCCs (60%) compared with the normal counterparts. The ANGPTL3 expression level was correlated closely (P < 0.05) with tumoral size. In patients with T3/T4 tumors, the overall survival rate with an ANGPTL3-positive tumor was significantly (P < 0.05) lower than that of ANGPTL3-negative cases. In vitro, cellular growth in ANGPTL3 knockdown cells significantly (P < 0.05) decreased with inactivated extracellular regulated kinase (ERK) and cell-cycle arrest at the G1 phase resulting from upregulation of the cyclin-dependent kinase inhibitors, including p21 Cip1 and p27 Kip1 . We also observed a marked (P < 0.05) reduction in the growth in ANGPTL3 knockdown-cell xenografts with decreased levels of phosphorylated ERK relative to control-cell xenografts. The current data indicated that ANGPTL3 may play a role in OSCCs via MAPK signaling cascades, making it a potentially useful diagnostic/therapeutic target for use in patients with OSCC

  17. Leading edge vortices in lesser long-nosed bats occurring at slow but not fast flight speeds

    International Nuclear Information System (INIS)

    Muijres, Florian T; Christoffer Johansson, L; Hedenström, Anders; Winter, York

    2014-01-01

    Slow and hovering animal flight creates high demands on the lift production of animal wings. Steady state aerodynamics is unable to explain the forces required and the most commonly used mechanism to enhance the lift production is a leading edge vortex (LEV). Although LEVs increase the lift, they come at the cost of high drag. Here we determine the flow above the wing of lesser long-nosed bats at slow and cruising speed using particle image velocimetry (PIV). We find that a prominent LEV is present during the downstroke at slow speed, but not at cruising speed. Comparison with previously published LEV data from a robotic flapper inspired by lesser long-nosed bats suggests that bats should be able to generate LEVs at cruising speeds, but that they avoid doing so, probably to increase flight efficiency. In addition, at slow flight speeds we find LEVs of opposite spin at the inner and outer wing during the upstroke, potentially providing a control challenge to the animal. We also note that the LEV stays attached to the wing throughout the downstoke and does not show the complex structures found in insects. This suggests that bats are able to control the development of the LEV and potential control mechanisms are discussed. (papers)

  18. Repair of lesser tuberosity osteotomy for shoulder arthroplasty: biomechanical evaluation of the Backpack and Dual Row techniques.

    Science.gov (United States)

    Heckman, Daniel S; Hoover, Stephen A; Weinhold, Paul S; Spang, Jeffrey T; Creighton, R Alexander

    2011-04-01

    Subscapularis dysfunction following total shoulder arthroplasty can result in permanent loss of function. The lesser tuberosity osteotomy (LTO) has been proposed as a method which utilizes bone-to-bone healing to improve subscapularis function. This study evaluates the biomechanical properties of two described techniques for LTO repair. We hypothesized that a Dual Row repair would be stronger and demonstrate less cyclic displacement than a Backpack repair. Ten matched pairs of cadaveric humeri were dissected, leaving the subscapularis intact, and a lesser tuberosity osteotomy was performed. Matched shoulders were randomized to either a Backpack repair or a Dual Row repair. Repairs were subjected to cyclic loading to 180 N for 500 cycles, followed by ramp-up loading to ultimate failure. Clinical failure was defined as displacement >5 mm after 500 cycles. Displacement after 500 cycles was significantly greater for the Backpack repair (6.9 mm) than for the Dual Row repair (4.6 mm) (P = .007). Most displacement occurred on the first cycle (Backpack, 4.6 mm; Dual Row, 2.1 mm) (P Row repair (3/10). Ultimate tensile strength was significantly greater for the Dual Row repair (632.3 N) than for the Backpack repair (510.9 N) (P = .01). The Dual Row technique is significantly stronger and demonstrates less cyclic displacement than the Backpack technique. Clinical studies are needed to determine the impact of LTO repair technique on subscapularis function following shoulder arthroplasty. Copyright © 2011. Published by Mosby, Inc.

  19. Melaleuca alternifolia Essential Oil against the Lesser Mealworm (Alphitobius diaperinus and Its Possible Effect on the Soil Fauna

    Directory of Open Access Journals (Sweden)

    A Volpato

    2016-03-01

    Full Text Available ABSTRACT The aim of this study was to evaluate the in vitro bioactivity of tea tree (Melaleuca alternifolia essential oil against larvae and adult forms of lesser mealworms (Alphitobius diaperinus and its influence on the soil fauna. Tests were performed in triplicate using pure tea tree oil (TTO; 1, 5, 10, 25, 50, and 100%, TTO nanoparticles (1, 3, and 7.5%, or terpinen-4-ol, the main compound of the tea tree oil, at the same concentrations of TTO. Larvae and adult mortality occurred at concentrations up to 10 and 50% of TTO, respectively. No larvicidal or insecticidal effect of TTO nanoparticles was observed. Terpinen-4-ol showed insecticidal and larvicidal effect at concentrations higher than 25%. The evaluation of TTO effect on soil organisms was performed by standard ecotoxicological tests (ISO with the springtail species Folsomia candida. Only TTO was used for ecotoxicological tests in doses of 1, 5, 10, 25, 50, and 100 mg kg-1 of soil. TTO had no negative effects on F. candida survival or reproduction. Therefore, it was concluded that M. alternifolia oil may be a new alternative for control of the lesser mealworm.

  20. Trauma centers with higher rates of angiography have a lesser incidence of splenectomy in the management of blunt splenic injury.

    Science.gov (United States)

    Capecci, Louis M; Jeremitsky, Elan; Smith, R Stephen; Philp, Frances

    2015-10-01

    Nonoperative management (NOM) for blunt splenic injury (BSI) is well-established. Angiography (ANGIO) has been shown to improve success rates with NOM. Protocols for NOM are not standardized and vary widely between centers. We hypothesized that trauma centers that performed ANGIO at a greater rate would demonstrate decreased rates of splenectomy compared with trauma centers that used ANGIO less frequently. A large, multicenter, statewide database (Pennsylvania Trauma Systems Foundation) from 2007 to 2011 was used to generate the study cohort of patients with BSI (age ≥ 13). The cohort was divided into 2 populations based on admission to centers with high (≥13%) or low (Splenectomy rates were then compared between the 2 groups, and multivariable logistic regression for predictors of splenectomy (failed NOM) were also performed. The overall rate of splenectomy in the entire cohort was 21.0% (1,120 of 5,333 BSI patients). The high ANGIO group had a lesser rate of splenectoy compared with the low ANGIO group (19% vs 24%; P splenectomy compared with low ANGIO centers (odds ratio, 0.68; 95% CI 0.58-0.80; P splenectomy rates compared with centers with lesser rate of ANGIO. Inclusion of angiographic protocols for NOM of BSI should be considered strongly. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Inhibition of Colon Carcinoma Cell Migration Following Treatment with Purified Venom from Lesser Weever Fish (Trachinus Vipera

    Directory of Open Access Journals (Sweden)

    Myriam Fezai

    2017-04-01

    Full Text Available Background: Injury by the sting of Lesser weever fish (Trachinus vipera may lead to severe pain, edema or tissue necrosis. Cellular effects of the venom are still incompletely understood. Previous observations revealed that purified Lesser weever fish venom (LWFV induces suicidal death of erythrocytes and HCT116 human colon carcinoma cells. The present study addressed the effect of the venom on colon carcinoma cell toxicity, shape and migration both in p53+/+ and/or p53-/- conditions. Methods: Cells were exposed to medium without or with 500 µg/ ml LWFV. Cell shape, cell area and circularity were visualized and quantified by fluorescence microscopy. Cell volume, granularity and cells toxicity were assessed via the apoptotic parameters dissipation of mitochondrial inner transmembrane potential, phosphatidylserine surface exposure and cell membrane permeabilization were measured utilizing flow cytometry. Cell migration was evaluated using wound healing assay and two-dimensional migration assay. Results: LWFV treatment was followed by a marked change of cell shape and size, significant decrease of cell area and circularity, significant impairment of cell migration, as well as induction of apoptosis after long exposition. Conclusions: LWFV exposure leads to cell shrinkage, increased granularity, apoptosis and impairment of cell migration, effects presumably contributing to LWFV-induced tissue injury.

  2. GPS tracking data of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coast.

    Science.gov (United States)

    Stienen, Eric W M; Desmet, Peter; Aelterman, Bart; Courtens, Wouter; Feys, Simon; Vanermen, Nicolas; Verstraete, Hilbran; de Walle, Marc Van; Deneudt, Klaas; Hernandez, Francisco; Houthoofdt, Robin; Vanhoorne, Bart; Bouten, Willem; Buijs, Roland-Jan; Kavelaars, Marwa M; Müller, Wendt; Herman, David; Matheve, Hans; Sotillo, Alejandro; Lens, Luc

    2016-01-01

    In this data paper, Bird tracking - GPS tracking of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coast is described, a species occurrence dataset published by the Research Institute for Nature and Forest (INBO). The dataset (version 5.5) contains close to 2.5 million occurrences, recorded by 101 GPS trackers mounted on 75 Lesser Black-backed Gulls and 26 Herring Gulls breeding at the Belgian and Dutch coast. The trackers were developed by the University of Amsterdam Bird Tracking System (UvA-BiTS, http://www.uva-bits.nl). These automatically record and transmit bird movements, which allows us and others to study their habitat use and migration behaviour in great detail. Our bird tracking network is operational since 2013. It is funded for LifeWatch by the Hercules Foundation and maintained in collaboration with UvA-BiTS and the Flanders Marine Institute (VLIZ). The recorded data are periodically released in bulk as open data (http://dataset.inbo.be/bird-tracking-gull-occurrences), and are also accessible through CartoDB and the Global Biodiversity Information Facility (GBIF).

  3. Seismic tomography of Basse-Terre volcanic island, Guadeloupe, Lesser Antilles, using earthquake travel times and noise correlations

    Science.gov (United States)

    Barnoud, Anne; Coutant, Olivier; Bouligand, Claire; Massin, Frédérick; Stehly, Laurent

    2015-04-01

    We image the volcanic island of Basse-Terre, Guadeloupe, Lesser Antilles, using both earthquake travel times and noise correlations. (1) A new earthquake catalog was recently compiled for the Lesser Antilles by the CDSA/OVSG/IPGP (Massin et al., EGU General Assembly 2014) and allows us to perform classical travel time tomography to obtain smooth 3D body wave velocity models. The geometrical configuration of the volcanic arc controls the resolution of the model in our zone of interest. (2) Surface wave tomography using noise correlations was successfully applied to volcanoes (Brenguier et al., Geophys. Res. Lett. 2007). We use seismic noise recorded at 16 broad-band stations and 9 short-period stations from Basse-Terre over a period of six years (2007-2012). For each station pair, we extract a dispersion curve from the noise correlation to get surface wave velocity models. The inversion of the dispersion curves produces a 3D S-wave velocity model of the island. The spatial distribution of seismic stations accross the island is highly heterogeneous, leading to higher resolution near the dome of the Soufrière of Guadeloupe volcano. Resulting velocity models are compared with densities obtained by 3D inversion of gravimetric data (Barnoud et al., AGU Fall Meeting 2013). Further work should include simultaneous inversion of seismic and gravimetric datasets to overcome resolution limitations.

  4. Hepatitis C virus E2 protein promotes human hepatoma cell proliferation through the MAPK/ERK signaling pathway via cellular receptors

    International Nuclear Information System (INIS)

    Zhao Lanjuan; Wang Lu; Ren Hao; Cao Jie; Li Li; Ke Jinshan; Qi Zhongtian

    2005-01-01

    Dysregulation of mitogen-activated protein kinase (MAPK) signaling pathways by various viruses has been shown to be responsible for viral pathogenicity. The molecular mechanism by which hepatitis C virus (HCV) infection caused human liver diseases has been investigated on the basis of abnormal intracellular signal events. Current data are very limited involved in transmembrane signal transduction triggered by HCV E2 protein. Here we explored regulation of the MAPK/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by E2 expressed in Chinese hamster oval cells. In human hepatoma Huh-7 cells, E2 specifically activated the MAPK/ERK pathway including downstream transcription factor ATF-2 and greatly promoted cell proliferation. CD81 and low density lipoprotein receptor (LDLR) on the cell surface mediated binding of E2 to Huh-7 cells. The MAPK/ERK activation and cell proliferation driven by E2 were suppressed by blockage of CD81 as well as LDLR. Furthermore, pretreatment with an upstream kinase MEK1/2 inhibitor U0126 also impaired the MAPK/ERK activation and cell proliferation induced by E2. Our results suggest that the MAPK/ERK signaling pathway triggered by HCV E2 via its receptors maintains survival and growth of target cells

  5. The extent of emphysema in patients with COPD

    DEFF Research Database (Denmark)

    Shaker, Saher Burhan; Stavngaard, Trine; Hestad, Marianne

    2009-01-01

    BACKGROUND AND AIMS: The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate...... measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below -910 Hounsfield units (RA-910) was extracted. RESULTS: Mean RA-910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV....... Regression analysis showed a change in RA-910 of 7.8% with increasing severity according to GOLD stage (P emphysema, whereas 25 patients had no emphysema. CONCLUSION: The extent of emphysema...

  6. Extent of hippocampal atrophy predicts degree of deficit in recall.

    Science.gov (United States)

    Patai, Eva Zita; Gadian, David G; Cooper, Janine M; Dzieciol, Anna M; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-10-13

    Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

  7. A report on the extent of radioisotope usage in Malaysia

    International Nuclear Information System (INIS)

    1983-04-01

    A market survey was carried out to study the extent of radioisotope usage in Malaysia. From the survey, the radioisotopes and their activities/quantities that are used in Industry, Medicine and Research were identified. The radioisotopes that are frequently needed or routinely used were also determined and this formed the basis of the recommendations put forward in this report. It is proposed that PUSPATI adopt the concept of a Distribution Centre in order to provide a service to the Malaysian community. (author)

  8. The extent and impact of outsourcing: evidence from Germany

    OpenAIRE

    Craig P. Aubuchon; Subhayu Bandyopadhyay; Sumon Bhaumik

    2012-01-01

    The authors use data from several sources, including plant-level data from the manufacturing sector in Germany, to expand the literature on outsourcing. They find that, in Germany, the extent of outsourcing among manufacturing industries is higher than among service industries and that the outsourcing intensity of these industries did not change much between 1995 and 2005. They also find a statistically significantly positive impact of industry-level outsourcing intensity on German plant-leve...

  9. Statistics of Radial Ship Extent as Seen by a Seeker

    Science.gov (United States)

    2014-06-01

    Auckland in pure and applied mathematics and physics, and a Master of Science in physics from the same university with a thesis in applied accelerator...does not demand contributions from two angle bins to one extent bin, unlike the rectangle; this is a very big advantage of the ellipse model. However...waveform that mimics the full length of a ship. This allows more economical use to be made of available false-target generation resources. I wish to

  10. Genetic evidence of hybridization between the endangered native species Iguana delicatissima and the invasive Iguana iguana (Reptilia, Iguanidae) in the Lesser Antilles: management Implications

    OpenAIRE

    Vuillaume, Barbara; Valette, Victorien; Lepais, Olivier; Grandjean, Frederic; Breuil, Michel

    2015-01-01

    The worldwide increase of hybridization in different groups is thought to have become more important with the loss of isolating barriers and the introduction of invasive species. This phenomenon could result in the extinction of endemic species. This study aims at investigating the hybridization dynamics between the endemic and threatened Lesser Antillean iguana (Iguana delicatissima) and the invasive common green iguana (Iguana iguana) in the Lesser Antilles, as well as assessing the impact ...

  11. Radiographically breedspecific morphology and calcifying tendinopathy in the Iliopsoas muscle at the lesser trochanter in Rottweilers, German Shepherd dogs and Bavarian Mountain hounds

    OpenAIRE

    Willmitzer, Florian; Gumpenberger, Michaela; Sommerfeld-Stur, Irene; Mayrhofer, Elisabeth

    2016-01-01

    The purpose of this retrospective study is to describe the radiographic morphology of the lesser trochanter as well as possible enthesiopathies of the iliopsoas muscle in Rottweilers, German Shepherd Dogs and Bavarian Mountain Hounds. The normal shape of the lesser trochanter appeared radiological triangular in German Shepherd Dogs and blunt or bump like in Rottweilers and Bavarian Mountain Hounds. Changes indicating an enthesiopathy presented as periosteal blurrings, variation in shape or in...

  12. Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats.

    Science.gov (United States)

    Fang, Jian-Qiao; Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan

    2013-03-22

    Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.

  13. To what extent can the nuclear public relations be effective?

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Teruaki [CRC Research Institute, Tokyo (Japan)

    1996-06-01

    The effect of public relations (PRs) on the public`s attitude to nuclear energy was assessed using a model developed under the assumption that the extent of attitude change of the public by the PRs activity is essentially the same as that by the nuclear information released by the newsmedia. The attitude change of the public was quantitatively estimated by setting variables explicitly manifesting the activities such as the circulation of exclusive publicity and the area of advertising messages in the newspaper as parameters. The public`s attitude became clear to have a nonlinear dependence on the amount of activity, the extent of its change being varied considerably with demographic classes. Under a given financial condition, the offer of PRs information to the people, as many as possible in a target region, in spite of its little force of appeal, was found to be more effective for the amelioration of public attitude than the repeated offer of the information to a limited member of the public. It also became clear that there exists the most effective media mix for the activity depending on the extent of target region and on the target class of demography, therefore, it is quite significant to determine beforehand the proper conditions for the activity to be executed, such a situation indicating the need for the introduction of nuclear PRs management. (Author).

  14. Regional Mapping of Plantation Extent Using Multisensor Imagery

    Science.gov (United States)

    Torbick, N.; Ledoux, L.; Hagen, S.; Salas, W.

    2016-12-01

    Industrial forest plantations are expanding rapidly across the tropics and monitoring extent is critical for understanding environmental and socioeconomic impacts. In this study, new, multisensor imagery were evaluated and integrated to extract the strengths of each sensor for mapping plantation extent at regional scales. Three distinctly different landscapes with multiple plantation types were chosen to consider scalability and transferability. These were Tanintharyi, Myanmar, West Kalimantan, Indonesia, and southern Ghana. Landsat-8 Operational Land Imager (OLI), Phased Array L-band Synthetic Aperture Radar-2 (PALSAR-2), and Sentinel-1A images were fused within a Classification and Regression Tree (CART) framework using random forest and high-resolution surveys. Multi-criteria evaluations showed both L-and C-band gamma nought γ° backscatter decibel (dB), Landsat reflectance ρλ, and texture indices were useful for distinguishing oil palm and rubber plantations from other land types. The classification approach identified 750,822 ha or 23% of the Taninathryi, Myanmar, and 216,086 ha or 25% of western West Kalimantan as plantation with very high cross validation accuracy. The mapping approach was scalable and transferred well across the different geographies and plantation types. As archives for Sentinel-1, Landsat-8, and PALSAR-2 continue to grow, mapping plantation extent and dynamics at moderate resolution over large regions should be feasible.

  15. To what extent can the nuclear public relations be effective?

    International Nuclear Information System (INIS)

    Ohnishi, Teruaki

    1996-01-01

    The effect of public relations (PRs) on the public's attitude to nuclear energy was assessed using a model developed under the assumption that the extent of attitude change of the public by the PRs activity is essentially the same as that by the nuclear information released by the newsmedia. The attitude change of the public was quantitatively estimated by setting variables explicitly manifesting the activities such as the circulation of exclusive publicity and the area of advertising messages in the newspaper as parameters. The public's attitude became clear to have a nonlinear dependence on the amount of activity, the extent of its change being varied considerably with demographic classes. Under a given financial condition, the offer of PRs information to the people, as many as possible in a target region, in spite of its little force of appeal, was found to be more effective for the amelioration of public attitude than the repeated offer of the information to a limited member of the public. It also became clear that there exists the most effective media mix for the activity depending on the extent of target region and on the target class of demography, therefore, it is quite significant to determine beforehand the proper conditions for the activity to be executed, such a situation indicating the need for the introduction of nuclear PRs management. (Author)

  16. Exploring the Origin, Extent, and Future of Life

    Science.gov (United States)

    Bertka, Constance M.

    2009-09-01

    1. Astrobiology in societal context Constance Bertka; Part I. Origin of Life: 2. Emergence and the experimental pursuit of the origin of life Robert Hazen; 3. From Aristotle to Darwin, to Freeman Dyson: changing definitions of life viewed in historical context James Strick; 4. Philosophical aspects of the origin-of-life problem: the emergence of life and the nature of science Iris Fry; 5. The origin of terrestrial life: a Christian perspective Ernan McMullin; 6. The alpha and the omega: reflections on the origin and future of life from the perspective of Christian theology and ethics Celia Deane-Drummond; Part II. Extent of Life: 7. A biologist's guide to the Solar System Lynn Rothschild; 8. The quest for habitable worlds and life beyond the Solar System Carl Pilcher; 9. A historical perspective on the extent and search for life Steven J. Dick; 10. The search for extraterrestrial life: epistemology, ethics, and worldviews Mark Lupisella; 11. The implications of discovering extraterrestrial life: different searches, different issues Margaret S. Race; 12. God, evolution, and astrobiology Cynthia S. W. Crysdale; Part III. Future of Life: 13. Planetary ecosynthesis on Mars: restoration ecology and environmental ethics Christopher P. McKay; 14. The trouble with intrinsic value: an ethical primer for astrobiology Kelly C. Smith; 15. God's preferential option for life: a Christian perspective on astrobiology Richard O. Randolph; 16. Comparing stories about the origin, extent, and future of life: an Asian religious perspective Francisca Cho; Index.

  17. Monitoring the Extent of Forests on National to Global Scales

    Science.gov (United States)

    Townshend, J.; Townshend, J.; Hansen, M.; DeFries, R.; DeFries, R.; Sohlberg, R.; Desch, A.; White, B.

    2001-05-01

    Information on forest extent and change is important for many purposes, including understanding the global carbon cycle and managing natural resources. International statistics on forest extent are generated using many different sources often producing inconsistent results spatially and through time. Results will be presented comparing forest extent derived from the recent global Food and Agricultural Organization's (FAO) FRA 2000 report with products derived using wall-to-wall Landsat, AVHRR and MODIS data sets. The remotely sensed data sets provide consistent results in terms of total area despite considerable differences in spatial resolution. Although the location of change can be satisfactorily detected with all three remotely sensed data sets, reliable measurement of change can only be achieved through use of Landsat-resolution data. Contrary to the FRA 2000 results we find evidence of an increase in deforestation rates in the late 1990s in several countries. Also we have found evidence of considerable changes in some countries for which little or no change is reported by FAO. The results indicate the benefits of globally consistent analyses of forest cover based on multiscale remotely sensed data sets rather than a reliance on statistics generated by individual countries with very different definitions of forest and methods used to derive them.

  18. The extent of emphysema in patients with COPD.

    Science.gov (United States)

    Shaker, Saher Burhan; Stavngaard, Trine; Hestad, Marianne; Bach, Karen Skjoelstrup; Tonnesen, Philip; Dirksen, Asger

    2009-01-01

    The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate this extent to the GOLD stage of airway obstruction. We included 209 patients with COPD. COPD was defined as FEV(1)/FVC or=20 pack-years. Patients were assessed by lung function measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below -910 Hounsfield units (RA-910) was extracted. Mean RA-910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV. Regression analysis showed a change in RA-910 of 7.8% with increasing severity according to GOLD stage (P < 0.001). Combined visual and quantitative assessment of CT showed that 184 patients had radiological evidence of emphysema, whereas 25 patients had no emphysema. The extent of emphysema increases with increasing severity of COPD and most patients with COPD have emphysema. Tissue destruction by emphysema is therefore an important determinant of disease severity in COPD.

  19. Geodynamics and Stress State of the Earth's Crust in the Greater and Lesser Caucasus (Azerbaijan) collision region

    Science.gov (United States)

    Babayev, Gulam; Akhmedova, Elnare; Babayev, Elvin

    2017-04-01

    The current study researches the present-day stress state of the Earth's crust within the territory of Azerbaijan by using the database of the international research project "World Stress Map" (WSM). The present stress state was also assessed by exploring the effects of the contemporary topographic properties of Caucasus in three-dimensional frame. Aiming to explore the relative roles of regional tectonic conditions in the definition of stress state of Greater and Lesser Caucasus, stress distribution model was developed by the earthquake data (1998-2016) and by the standard techniques of stress field calculation. The results show that the stress orientations are influenced also by the combination of topography and crust thickness distribution even at very large depth. Stress data and earthquake focal mechanisms indicate that the stress state of the Earth's crust of the Greater and Lesser Caucasus is characterized by the compression predominantly oriented across the regional strike. The model results suggest that the Lesser Caucasus and Kur depression are rotating coherently, with little or no internal deformation in a counter-clockwise rotation located near the north-eastern corner of the Black Sea. Orientation of stress axes well consistent with earthquake focal mechanisms revealed that within Upper and Lower Crusts, earthquakes are predominantly thrust-faulting with a number of normal-faulting and some strike-slip faulting. The map of the focal mechanisms and stress distribution suggests that the research area is characterized by the thrust of horizontal compression trending north-north-east in the western part of the southern Caucasus. In the western part of Azerbaijan, the compression takes place between the Main Caucasus Fault and the Kur depression, which strikes south along the northern margin of the mountain range. In addition, a clear transition from the left-lateral strike slip to the predominantly right-lateral strike slip is observed in the southern of

  20. Tectonic implications of U-Pb (zircon) Geochronology of Chor Granitoids of the Lesser Himalaya, Himachal Pradesh, NW Himalaya

    Science.gov (United States)

    Singh, P.; Bhakuni, S. S.

    2017-12-01

    Granitoids of various ages ranging from Proterozoic to Tertiary occur throughout the Himalayan fold-thrust belt. The occurrence of the Neoproterozoic granitoids are very less in the Himalayan orogen. One of the best example of Neoproterozoic granitoids is Chor granitoids, which are the intrusive granite bodies in the Paleoproterozoic of the Lesser Himalayan Crystallines of the Jutogh Group. In the central part these granites are non-foliated homogeneous that are porphyritic and peraluminous in nature (Singh et al., 2002; Bhargava et al., 2014, 2016), whereas in the peripheral part these are foliated showing south directed shear sense of movement. In this work we present the U-Pb (zircon) geochronology of two different granites samples of the Chor granitoids of Himachal Pradesh, NW Himalaya. The Jutogh Group of rocks is thrust over the Lesser Himalayan Sequence along the Jutogh Thrust or MCT. The geochronology of the Chor Granitoids and Lesser Himalayan Crystallines and their relationship with each other, including with the Indian shield are sparsely obscure. U-Pb zircon geochrnological age populations from these granitoids yield ages between 780 and 980 Ma. One sample gives the prominent age spectra for 206Pb/238U with weighted mean age of 908.3 ± 6.7 Ma (2σ) MSWD = 2.4 (n = 18). Similarly another sample gives the age of crystallization with weight mean age of 917 ± 17 Ma (2σ) MSWD = 3 (n = 11) and Th/U ratios of both samples are >0.1, indicating their magmatic origin. As a result of ductile shearing of granites along the MCT during the Cenozoic Himalayan Orogeny, the age has reduced to 780 Ma. The Neoproterozoic age of Chor granite matches with the Neoproterozoic detrital zircon age (800 to 1000 Ma by Parrish and Hodges 1996, Decelles et al., 2000) of the HHC. On the basis of U-Pb (zircon) geochronological ages, it is revealed that the source of zircons of the Chor granite and HHC rocks was the northern margin of the Pan-African orogen. The Chor granitoids was

  1. Interleukin-6 stimulates Akt and p38 MAPK phosphorylation and fibroblast migration in non-diabetic but not diabetic mice.

    Directory of Open Access Journals (Sweden)

    Tsubame Nishikai-Yan Shen

    Full Text Available Persistent inflammatory environment and abnormal macrophage activation are characteristics of chronic diabetic wounds. Here, we attempted to characterize the differences in macrophage activation and temporal variations in cytokine expression in diabetic and non-diabetic wounds, with a focus on interleukin (IL-6 mRNA expression and the p38 MAPK and PI3K/Akt signaling pathways. Cutaneous wound closure, CD68- and arginase-1 (Arg-1-expressing macrophages, and cytokine mRNA expression were examined in non-diabetic and streptozotocin-induced type 1 diabetic mice at different time points after injury. The effect of IL-6 on p38 MAPK and Akt phosphorylation was investigated, and an in vitro scratch assay was performed to determine the role of IL-6 in primary skin fibroblast migration. Before injury, mRNA expression levels of the inflammatory markers iNOS, IL-6, and TNF-α were higher in diabetic mice; however, IL-6 expression was significantly lower 6 h post injury in diabetic wounds than that in non-diabetic wounds. Non-diabetic wounds exhibited increased p38 MAPK and Akt phosphorylation; however, no such increase was found in diabetic wounds. In fibroblasts from non-diabetic mice, IL-6 increased the phosphorylation of p38 MAPK and levels of its downstream factor CREB, and also significantly increased Akt phosphorylation and levels of its upstream factor P13K. These effects of IL-6 were not detected in fibroblasts derived from the diabetic mice. In scratch assays, IL-6 stimulated the migration of primary cultured skin fibroblasts from the non-diabetic mice, and the inhibition of p38 MAPK was found to markedly suppress IL-6-stimulated fibroblast migration. These findings underscore the critical differences between diabetic and non-diabetic wounds in terms of macrophage activation, cytokine mRNA expression profile, and involvement of the IL-6-stimulated p38 MAPK-Akt signaling pathway. Aberrant macrophage activation and abnormalities in the cytokine m

  2. A Global Geospatial Database of 5000+ Historic Flood Event Extents

    Science.gov (United States)

    Tellman, B.; Sullivan, J.; Doyle, C.; Kettner, A.; Brakenridge, G. R.; Erickson, T.; Slayback, D. A.

    2017-12-01

    A key dataset that is missing for global flood model validation and understanding historic spatial flood vulnerability is a global historical geo-database of flood event extents. Decades of earth observing satellites and cloud computing now make it possible to not only detect floods in near real time, but to run these water detection algorithms back in time to capture the spatial extent of large numbers of specific events. This talk will show results from the largest global historical flood database developed to date. We use the Dartmouth Flood Observatory flood catalogue to map over 5000 floods (from 1985-2017) using MODIS, Landsat, and Sentinel-1 Satellites. All events are available for public download via the Earth Engine Catalogue and via a website that allows the user to query floods by area or date, assess population exposure trends over time, and download flood extents in geospatial format.In this talk, we will highlight major trends in global flood exposure per continent, land use type, and eco-region. We will also make suggestions how to use this dataset in conjunction with other global sets to i) validate global flood models, ii) assess the potential role of climatic change in flood exposure iii) understand how urbanization and other land change processes may influence spatial flood exposure iv) assess how innovative flood interventions (e.g. wetland restoration) influence flood patterns v) control for event magnitude to assess the role of social vulnerability and damage assessment vi) aid in rapid probabilistic risk assessment to enable microinsurance markets. Authors on this paper are already using the database for the later three applications and will show examples of wetland intervention analysis in Argentina, social vulnerability analysis in the USA, and micro insurance in India.

  3. Extent of pyrolysis impacts on fast pyrolysis biochar properties.

    Science.gov (United States)

    Brewer, Catherine E; Hu, Yan-Yan; Schmidt-Rohr, Klaus; Loynachan, Thomas E; Laird, David A; Brown, Robert C

    2012-01-01

    A potential concern about the use of fast pyrolysis rather than slow pyrolysis biochars as soil amendments is that they may contain high levels of bioavailable C due to short particle residence times in the reactors, which could reduce the stability of biochar C and cause nutrient immobilization in soils. To investigate this concern, three corn ( L.) stover fast pyrolysis biochars prepared using different reactor conditions were chemically and physically characterized to determine their extent of pyrolysis. These biochars were also incubated in soil to assess their impact on soil CO emissions, nutrient availability, microorganism population growth, and water retention capacity. Elemental analysis and quantitative solid-state C nuclear magnetic resonance spectroscopy showed variation in O functional groups (associated primarily with carbohydrates) and aromatic C, which could be used to define extent of pyrolysis. A 24-wk incubation performed using a sandy soil amended with 0.5 wt% of corn stover biochar showed a small but significant decrease in soil CO emissions and a decrease in the bacteria:fungi ratios with extent of pyrolysis. Relative to the control soil, biochar-amended soils had small increases in CO emissions and extractable nutrients, but similar microorganism populations, extractable NO levels, and water retention capacities. Corn stover amendments, by contrast, significantly increased soil CO emissions and microbial populations, and reduced extractable NO. These results indicate that C in fast pyrolysis biochar is stable in soil environments and will not appreciably contribute to nutrient immobilization. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  4. Preparation of industrial chemicals by acid leaching from the koga nepheline syenite, southern Swat, lesser Himalayas-Pakistan

    International Nuclear Information System (INIS)

    Nizami, A.R.

    2012-01-01

    This paper encompasses the study on the preparation of industrial chemicals by acid leaching from the Koga nepheline syenite, Southern Swat, Lesser Himalayas-Pakistan. These rocks have been studied in detail by many workers to exploit their industrial utility in the form of powdered rock material in glass and ceramics and steel industry. The present authors for the first time carried out acid leaching studies and prepared a number of industrial chemicals, like, alumina, aluminium sulphate, sodium and ammonium alums, sodium sulphate) and sodium bisulphate by simple chemical reactions at bench scale successfully. The developed process is simple and economically viable. It is recommended to exploit this process in cottage industry in the mountainous areas hosting these rocks for the benefit of local population. The research and development work for production of these chemicals at pilot plant and industrial scale is recommended as well. (author)

  5. Detecting the Extent of Eutectoid Transformation in U-10Mo

    Energy Technology Data Exchange (ETDEWEB)

    Devaraj, Arun [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jana, Saumyadeep [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McInnis, Colleen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lombardo, Nicholas J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Joshi, Vineet V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sweet, Lucas E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Manandhar, Sandeep [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lavender, Curt A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-08-31

    During eutectoid transformation of U-10Mo alloy, uniform metastable γ UMo phase is expected to transform to a mixture of α-U and γ’-U2Mo phase. The presence of transformation products in final U-10Mo fuel, especially the α phase is considered detrimental for fuel irradiation performance, so it is critical to accurately evaluate the extent of transformation in the final U-10Mo alloy. This phase transformation can cause a volume change that induces a density change in final alloy. To understand this density and volume change, we developed a theoretical model to calculate the volume expansion and resultant density change of U-10Mo alloy as a function of the extent of eutectoid transformation. Based on the theoretically calculated density change for 0 to 100% transformation, we conclude that an experimental density measurement system will be challenging to employ to reliably detect and quantify the extent of transformation. Subsequently, to assess the ability of various methods to detect the transformation in U-10Mo, we annealed U-10Mo alloy samples at 500°C for various times to achieve in low, medium, and high extent of transformation. After the heat treatment at 500°C, the samples were metallographically polished and subjected to optical microscopy and x-ray diffraction (XRD) methods. Based on our assessment, optical microscopy and image processing can be used to determine the transformed area fraction, which can then be correlated with the α phase volume fraction measured by XRD analysis. XRD analysis of U-10Mo aged at 500°C detected only α phase and no γ’ was detected. To further validate the XRD results, atom probe tomography (APT) was used to understand the composition of transformed regions in U-10Mo alloys aged at 500°C for 10 hours. Based on the APT results, the lamellar transformation product was found to comprise α phase with close to 0 at% Mo and γ phase with 28–32 at% Mo, and the Mo concentration was highest at the

  6. Extent of the Immirzi ambiguity in quantum general relativity

    International Nuclear Information System (INIS)

    Marugan, Guillermo A Mena

    2002-01-01

    The Ashtekar-Barbero formulation of general relativity admits a one-parameter family of canonical transformations that preserves the expressions of the Gauss and diffeomorphism constraints. The loop quantization of the connection formalism based on each of these canonical sets leads to different predictions. This phenomenon is called the Immirzi ambiguity. It has been recently argued that this ambiguity could be generalized to the extent of a spatially dependent function instead of a parameter. This would ruin the predictability of loop quantum gravity. We prove that such expectations are not realized, so that the Immirzi ambiguity introduces exclusively a freedom in the choice of a real number. (letter to the editor)

  7. Determination of extent of surgical intervention for endometrial carcinoma

    International Nuclear Information System (INIS)

    Smakhtina, O.L.; Nugmanova, M.I.; Nigaj, S.V.

    1986-01-01

    Clinical, cytologic, histologic and X-ray procedures were used in examining 120 patients with endometrial carcinoma. The results of pre- and intraoperative determination of clinical stage were compared in 65 cases of uterine extirpation with appendages and lymphadenectomy. Errors in preoperative identification of the extent of tumor expansion were made in 9 cases (13.8+-4.3%). It was found that determinations of the site and expansion of tumor make the case for hysterocervico-angiolymphography whereas identification of tumor pattern and degree of cell differentiation-for cytologic and histologic assays

  8. Detecting the Extent of Eutectoid Transformation in U-10Mo

    International Nuclear Information System (INIS)

    Devaraj, Arun; Jana, Saumyadeep; McInnis, Colleen A.; Lombardo, Nicholas J.; Joshi, Vineet V.; Sweet, Lucas E.; Manandhar, Sandeep; Lavender, Curt A.

    2016-01-01

    During eutectoid transformation of U-10Mo alloy, uniform metastable ? UMo phase is expected to transform to a mixture of ?-U and ?'-U_2Mo phase. The presence of transformation products in final U-10Mo fuel, especially the ? phase is considered detrimental for fuel irradiation performance, so it is critical to accurately evaluate the extent of transformation in the final U-10Mo alloy. This phase transformation can cause a volume change that induces a density change in final alloy. To understand this density and volume change, we developed a theoretical model to calculate the volume expansion and resultant density change of U-10Mo alloy as a function of the extent of eutectoid transformation. Based on the theoretically calculated density change for 0 to 100% transformation, we conclude that an experimental density measurement system will be challenging to employ to reliably detect and quantify the extent of transformation. Subsequently, to assess the ability of various methods to detect the transformation in U-10Mo, we annealed U-10Mo alloy samples at 500°C for various times to achieve in low, medium, and high extent of transformation. After the heat treatment at 500°C, the samples were metallographically polished and subjected to optical microscopy and x-ray diffraction (XRD) methods. Based on our assessment, optical microscopy and image processing can be used to determine the transformed area fraction, which can then be correlated with the ? phase volume fraction measured by XRD analysis. XRD analysis of U-10Mo aged at 500°C detected only ? phase and no ?' was detected. To further validate the XRD results, atom probe tomography (APT) was used to understand the composition of transformed regions in U-10Mo alloys aged at 500°C for 10 hours. Based on the APT results, the lamellar transformation product was found to comprise ? phase with close to 0 at% Mo and ? phase with 28-32 at% Mo, and the Mo concentration was highest at the ?/? interface.

  9. Measurement of extent of intense ion beam charge neutralization

    Energy Technology Data Exchange (ETDEWEB)

    Engelko, V [Efremov Institute of Electrophysical Apparatus, St. Petersburg (Russian Federation); Giese, H; Schalk, S [Forschungszentrum Karlsruhe (Germany). INR

    1997-12-31

    Various diagnostic tools were employed to study and optimize the extent of space charge neutralization in the pulsed intense proton beam facility PROFA, comprising Langmuir probes, capacitive probes, and a novel type of the three electrode collector. The latter does not only allow us to measure ion and electron beam current densities in a high magnetic field environment, but also to deduce the density spectrum of the beam electrons. Appropriate operating conditions were identified to attain a complete space charge neutralisation. (author). 5 figs., 4 refs.

  10. Rapid Estimates of Rupture Extent for Large Earthquakes Using Aftershocks

    Science.gov (United States)

    Polet, J.; Thio, H. K.; Kremer, M.

    2009-12-01

    The spatial distribution of aftershocks is closely linked to the rupture extent of the mainshock that preceded them and a rapid analysis of aftershock patterns therefore has potential for use in near real-time estimates of earthquake impact. The correlation between aftershocks and slip distribution has frequently been used to estimate the fault dimensions of large historic earthquakes for which no, or insufficient, waveform data is available. With the advent of earthquake inversions that use seismic waveforms and geodetic data to constrain the slip distribution, the study of aftershocks has recently been largely focused on enhancing our understanding of the underlying mechanisms in a broader earthquake mechanics/dynamics framework. However, in a near real-time earthquake monitoring environment, in which aftershocks of large earthquakes are routinely detected and located, these data may also be effective in determining a fast estimate of the mainshock rupture area, which would aid in the rapid assessment of the impact of the earthquake. We have analyzed a considerable number of large recent earthquakes and their aftershock sequences and have developed an effective algorithm that determines the rupture extent of a mainshock from its aftershock distribution, in a fully automatic manner. The algorithm automatically removes outliers by spatial binning, and subsequently determines the best fitting “strike” of the rupture and its length by projecting the aftershock epicenters onto a set of lines that cross the mainshock epicenter with incremental azimuths. For strike-slip or large dip-slip events, for which the surface projection of the rupture is recti-linear, the calculated strike correlates well with the strike of the fault and the corresponding length, determined from the distribution of aftershocks projected onto the line, agrees well with the rupture length. In the case of a smaller dip-slip rupture with an aspect ratio closer to 1, the procedure gives a measure

  11. Extent and application of patient diaries in Austria

    DEFF Research Database (Denmark)

    Heindl, Patrik; Bachlechner, Adelbert; Nydahl, Peter

    2017-01-01

    Background: Diaries written for patients in the intensive care unit (ICU) are offered in many European countries. In Austria, ICU diaries have been relatively unknown, but since 2012, they have started to emerge. Aim: The aim of this study was to explore the extent and application of ICU diaries...... in Austria in 2015. Method: The study had a prospective multiple methods design of survey and interviews. All ICUs in Austria were surveyed in 2015 to identify which ICUs used diaries. ICUs using diaries were selected for semi-structured key-informant telephone interviews on the application of ICU diaries...

  12. Integrating remotely sensed surface water extent into continental scale hydrology.

    Science.gov (United States)

    Revilla-Romero, Beatriz; Wanders, Niko; Burek, Peter; Salamon, Peter; de Roo, Ad

    2016-12-01

    In hydrological forecasting, data assimilation techniques are employed to improve estimates of initial conditions to update incorrect model states with observational data. However, the limited availability of continuous and up-to-date ground streamflow data is one of the main constraints for large-scale flood forecasting models. This is the first study that assess the impact of assimilating daily remotely sensed surface water extent at a 0.1° × 0.1° spatial resolution derived from the Global Flood Detection System (GFDS) into a global rainfall-runoff including large ungauged areas at the continental spatial scale in Africa and South America. Surface water extent is observed using a range of passive microwave remote sensors. The methodology uses the brightness temperature as water bodies have a lower emissivity. In a time series, the satellite signal is expected to vary with changes in water surface, and anomalies can be correlated with flood events. The Ensemble Kalman Filter (EnKF) is a Monte-Carlo implementation of data assimilation and used here by applying random sampling perturbations to the precipitation inputs to account for uncertainty obtaining ensemble streamflow simulations from the LISFLOOD model. Results of the updated streamflow simulation are compared to baseline simulations, without assimilation of the satellite-derived surface water extent. Validation is done in over 100 in situ river gauges using daily streamflow observations in the African and South American continent over a one year period. Some of the more commonly used metrics in hydrology were calculated: KGE', NSE, PBIAS%, R 2 , RMSE, and VE. Results show that, for example, NSE score improved on 61 out of 101 stations obtaining significant improvements in both the timing and volume of the flow peaks. Whereas the validation at gauges located in lowland jungle obtained poorest performance mainly due to the closed forest influence on the satellite signal retrieval. The conclusion is that

  13. Genetic favouring of pheomelanin-based pigmentation limits physiological benefits of coloniality in lesser kestrels Falco naumanni.

    Science.gov (United States)

    Galván, Ismael; Moraleda, Virginia; Otero, Ignacio; Álvarez, Ernesto; Inácio, Ângela

    2017-10-01

    Pheomelanin contributes to the pigmentation phenotype of animals by producing orange and light brown colours in the integument. However, pheomelanin synthesis in melanocytes requires consumption of glutathione (GSH), the most important intracellular antioxidant. Therefore, a genetic control favouring the production of large amounts of pheomelanin for pigmentation may lead to physiological costs under environmental conditions that promote oxidative stress. We investigated this possibility in the context of breeding coloniality, a reproductive strategy that may affect oxidative stress. We found in lesser kestrel Falco naumanni nestlings that the GSH:GSSG ratio, which decreases with systemic oxidative stress, increased with the size of the colony where they were reared, but the expression in feather melanocytes of five genes involved in pheomelanin synthesis (Slc7a11, Slc45a2, CTNS, MC1R and AGRP) did not vary with colony size. The antioxidant capacity (TEAC) of lesser kestrel nestlings also increased with colony size, but in a manner that depended on Slc7a11 expression and not on the expression of the other genes. Thus, antioxidant capacity increased with colony size only in nestlings least expressing Slc7a11, a gene with a known role in mediating cysteine (a constituent amino acid of GSH) consumption for pheomelanin production. The main predictor of the intensity of pheomelanin-based feather colour was Slc45a2 expression followed in importance by Slc7a11 expression, hence suggesting that the genetic regulation of the pigmentation phenotype mediated by Slc7a11 and a lack of epigenetic lability in this gene limits birds from benefiting from the physiological benefits of coloniality. © 2017 John Wiley & Sons Ltd.

  14. A meta-analysis of lesser prairie-chicken nesting and brood-rearing habitats: implications for habitat management

    Science.gov (United States)

    Hagen, Christian A.; Grisham, Blake A.; Boal, Clint W.; Haukos, David A.

    2013-01-01

    The distribution and range of lesser prairie-chicken (Tympanuchus pallidicinctus) has been reduced by >90% since European settlement of the Great Plains of North America. Currently, lesser prairie-chickens occupy 3 general vegetation communities: sand sagebrush (Artemisia filifolia), sand shinnery oak (Quercus havardii), and mixed-grass prairies juxtaposed with Conservation Reserve Program grasslands. As a candidate for protection under the Endangered Species Act, there is a need for a synthesis that characterizes habitat structure rangewide. Thus, we conducted a meta-analysis of vegetation characteristics at nest sites and brood habitats to determine whether there was an overall effect (Hedges' d) of habitat selection and to estimate average (95% CI) habitat characteristics at use sites. We estimated effect sizes (di) from the difference between use (nests and brood sites) and random sampling sites for each study (n = 14), and derived an overall effect size (d++). There was a general effect for habitat selection as evidenced by low levels of variation in effect sizes across studies and regions. There was a small to medium effect (d++) = 0.20-0.82) of selection for greater vertical structure (visual obstruction) by nesting females in both vegetation communities, and selection against bare ground (d++ = 0.20-0.58). Females with broods exhibited less selectivity for habitat components except for vertical structure. The variation of d++ was greater during nesting than brooding periods, signifying a seasonal shift in habitat use, and perhaps a greater range of tolerance for brood-rearing habitat. The overall estimates of vegetation cover were consistent with those provided in management guidelines for the species.

  15. Previous success and current body condition determine breeding propensity in Lesser Scaup: evidence for the individual heterogeneity hypothesis

    Science.gov (United States)

    Warren, Jeffrey M.; Cutting, Kyle A.; Takekawa, John Y.; De La Cruz, Susan E. W.; Williams, Tony D.; Koons, David N.

    2014-01-01

    The decision to breed influences an individual's current and future reproduction, and the proportion of individuals that breed is an important determinant of population dynamics. Age, experience, individual quality, and environmental conditions have all been demonstrated to influence breeding propensity. To elucidate which of these factors exerts the greatest influence on breeding propensity in a temperate waterfowl, we studied female Lesser Scaup (Aythya affinis) breeding in southwestern Montana. Females were captured during the breeding seasons of 2007–2009, and breeding status was determined on the basis of (1) presence of an egg in the oviduct or (2) blood plasma vitellogenin (VTG) levels. Presence on the study site in the previous year, a proxy for adult female success, was determined with stable isotope signatures of a primary feather collected at capture. Overall, 57% of females had evidence of breeding at the time of capture; this increased to 86% for females captured on or after peak nest initiation. Capture date and size-adjusted body condition positively influenced breeding propensity, with a declining body-condition threshold through the breeding season. We did not detect an influence of age on breeding propensity. Drought conditions negatively affected breeding propensity, reducing the proportion of breeding females to 0.85 (SE = 0.05) from 0.94 (SE = 0.03) during normal-water years. A female that was present in the previous breeding season was 5% more likely to breed than a female that was not present then. The positive correlation between age and experience makes it difficult to differentiate the roles of age, experience, and individual quality in reproductive success in vertebrates. Our results indicate that individual quality, as expressed by previous success and current body condition, may be among the most important determinants of breeding propensity in female Lesser Scaup, providing further support for the individual heterogeneity hypothesis.

  16. Reassessing the extent of the Q classification for containment paint

    International Nuclear Information System (INIS)

    Spires, G.

    1995-01-01

    A mounting number of site-specific paint debris transport and screen clogging analyses submitted to justify substandard containment paint work have been deemed persuasive by virtue of favorable U.S. Nuclear Regulatory Commission safety evaluation report (SER) findings. These lay a strong foundation for a standardized approach to redefining the extent to which paint in containment needs to be considered open-quotes Q.close quotes This information justifies an initiative by licensees to roll back paint work quality commitments made at the design phase. This paper questions the validity of the basic premise that all primary containment paint can significantly compromise core and containment cooling [emergency core cooling system/engineered safeguard feature (ECCS/ESF)]. It is posited that the physical extent of painted containment surfaces for which extant material qualification and quality control (QC) structures need apply can be limited to zones relatively proximate to ECCS/ESF suction points. For other painted containment surfaces, simplified criteria should be allowed

  17. The regional extent of suppression: strabismics versus nonstrabismics.

    Science.gov (United States)

    Babu, Raiju Jacob; Clavagnier, Simon R; Bobier, William; Thompson, Benjamin; Hess, Robert F

    2013-10-09

    Evidence is accumulating that suppression may be the cause of amblyopia rather than a secondary consequence of mismatched retinal images. For example, treatment interventions that target suppression may lead to better binocular and monocular outcomes. Furthermore, it has recently been demonstrated that the measurement of suppression may have prognostic value for patching therapy. For these reasons, the measurement of suppression in the clinic needs to be improved beyond the methods that are currently available, which provide a binary outcome. We describe a novel quantitative method for measuring the regional extent of suppression that is suitable for clinical use. The method involves a dichoptic perceptual matching procedure at multiple visual field locations. We compare a group of normal controls (mean age: 28 ± 5 years); a group with strabismic amblyopia (four with microesotropia, five with esotropia, and one with exotropia; mean age: 35 ± 10 years); and a group with nonstrabismic anisometropic amblyopia (mean age: 33 ± 12 years). The extent and magnitude of suppression was similar for observers with strabismic and nonstrabismic amblyopia. Suppression was strongest within the central field and extended throughout the 20° field that we measured. Suppression extends throughout the central visual field in both strabismic and anisometropic forms of amblyopia. The strongest suppression occurs within the region of the visual field corresponding to the fovea of the fixing eye.

  18. Corticocortical feedback increases the spatial extent of normalization.

    Science.gov (United States)

    Nassi, Jonathan J; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T

    2014-01-01

    Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a "normalization pool." Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing.

  19. Corticocortical feedback increases the spatial extent of normalization

    Science.gov (United States)

    Nassi, Jonathan J.; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T.

    2014-01-01

    Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a “normalization pool.” Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing. PMID:24910596

  20. Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

    Science.gov (United States)

    Yang, Cailing; Yan, Jianguo; Yuan, Guoyan; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Cui, Weigang

    2014-08-01

    Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

  1. Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

    Science.gov (United States)

    Centuori, Sara M; Martinez, Jesse D

    2014-10-01

    A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

  2. The third international meeting on genetic disorders in the RAS/MAPK pathway: towards a therapeutic approach.

    Science.gov (United States)

    Korf, Bruce; Ahmadian, Reza; Allanson, Judith; Aoki, Yoko; Bakker, Annette; Wright, Emma Burkitt; Denger, Brian; Elgersma, Ype; Gelb, Bruce D; Gripp, Karen W; Kerr, Bronwyn; Kontaridis, Maria; Lazaro, Conxi; Linardic, Corinne; Lozano, Reymundo; MacRae, Calum A; Messiaen, Ludwine; Mulero-Navarro, Sonia; Neel, Benjamin; Plotkin, Scott; Rauen, Katherine A; Roberts, Amy; Silva, Alcino J; Sittampalam, Sitta G; Zhang, Chao; Schoyer, Lisa

    2015-08-01

    "The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion. © 2015 Wiley Periodicals, Inc.

  3. Phenotypic and evolutionary implications of modulating the ERK-MAPK cascade using the dentition as a model

    Science.gov (United States)

    Marangoni, Pauline; Charles, Cyril; Tafforeau, Paul; Laugel-Haushalter, Virginie; Joo, Adriane; Bloch-Zupan, Agnès; Klein, Ophir D.; Viriot, Laurent

    2015-06-01

    The question of phenotypic convergence across a signalling pathway has important implications for both developmental and evolutionary biology. The ERK-MAPK cascade is known to play a central role in dental development, but the relative roles of its components remain unknown. Here we investigate the diversity of dental phenotypes in Spry2-/-, Spry4-/-, and Rsk2-/Y mice, including the incidence of extra teeth, which were lost in the mouse lineage 45 million years ago (Ma). In addition, Sprouty-specific anomalies mimic a phenotype that is absent in extant mice but present in mouse ancestors prior to 9 Ma. Although the mutant lines studied display convergent phenotypes, each gene has a specific role in tooth number determination and crown patterning. The similarities found between teeth in fossils and mutants highlight the pivotal role of the ERK-MAPK cascade during the evolution of the dentition in rodents.

  4. p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients

    DEFF Research Database (Denmark)

    Brown, Audrey E; Palsgaard, Jane; Borup, Rehannah

    2015-01-01

    Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic cultured myotubes, which is in keeping with a retained genetic/epigenetic defect of insulin action. We investigated differences in gene...... expression during differentiation between diabetic and control muscle cell cultures. Microarray analysis was performed using skeletal muscle cell cultures established from type 2 diabetic patients with a family history of type 2 diabetes and clinical evidence of marked insulin resistance and nondiabetic...... significantly, it did not improve insulin-stimulated glucose uptake. Increased cytokine expression driven by increased p38 MAPK activation is a key feature of cultured myotubes derived from insulin-resistant type 2 diabetic patients. p38 MAPK inhibition decreased cytokine expression but did not affect...

  5. Rosiglitazone attenuates NF-κB-dependent ICAM-1 and TNF-α production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation

    International Nuclear Information System (INIS)

    Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia; Song, Tao; You, Yu; Tang, Zhen-Yan; Li, Yuan-Jian; Zhang, Guo-Gang

    2007-01-01

    Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-κB) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-κB-mediated sICAM-1, TNF-α production and the possible involvement of ERK 1/2 /p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-α in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-κB inhibitor; PD98059, MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK 1/2 /p38MAPK pathway and NF-κB activity in HUVECs. The results show that Hcy activated both ERK 1/2 /p38MAPK pathway and NF-κB-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK 1/2 /p38MAPK phosphorylation, suggesting that Hcy-induced ERK 1/2 /p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-κB activation was mediated by activation of ERK 1/2 /p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-κB-mediated sICAM-1 and TNF-α production induced by Hcy via inhibition of ERK 1/2 /p38MAPK pathway

  6. Halofuginone inhibits Smad3 phosphorylation via the PI3K/Akt and MAPK/ERK pathways in muscle cells: Effect on myotube fusion

    International Nuclear Information System (INIS)

    Roffe, Suzy; Hagai, Yosey; Pines, Mark; Halevy, Orna

    2010-01-01

    Halofuginone, a novel inhibitor of Smad3 phosphorylation, has been shown to inhibit muscle fibrosis and to improve cardiac and skeletal muscle functions in the mdx mouse model of Duchenne muscular dystrophy. Here, we demonstrate that halofuginone promotes the phosphorylation of Akt and mitogen-activated protein kinase (MAPK) family members in a C2 muscle cell line and in primary myoblasts derived from wild-type and mdx mice diaphragms. Halofuginone enhanced the association of phosphorylated Akt and MAPK/extracellular signal-regulated protein kinase (ERK) with the non-phosphorylated form of Smad3, accompanied by a reduction in Smad3 phosphorylation levels. This reduction was reversed by inhibitors of the phosphoinositide 3'-kinase/Akt (PI3K/Akt) and MAPK/ERK pathways, suggesting their specific role in mediating halofuginone's inhibitory effect on Smad3 phosphorylation. Halofuginone enhanced Akt, MAPK/ERK and p38 MAPK phosphorylation and inhibited Smad3 phosphorylation in myotubes, all of which are crucial for myotube fusion. In addition, halofuginone increased the association Akt and MAPK/ERK with Smad3. As a consequence, halofuginone promoted myotube fusion, as reflected by an increased percentage of C2 and mdx myotubes containing high numbers of nuclei, and this was reversed by specific inhibitors of the PI3K and MAPK/ERK pathways. Together, the data suggest a role, either direct or via inhibition of Smad3 phosphorylation, for Akt or MAPK/ERK in halofuginone-enhanced myotube fusion, a feature which is crucial to improving muscle function in muscular dystrophies.

  7. Halofuginone inhibits Smad3 phosphorylation via the PI3K/Akt and MAPK/ERK pathways in muscle cells: Effect on myotube fusion

    Energy Technology Data Exchange (ETDEWEB)

    Roffe, Suzy [Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel); Hagai, Yosey [Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel); Institute of Animal Sciences, Volcani Center, Bet Dagan 50250 (Israel); Pines, Mark [Institute of Animal Sciences, Volcani Center, Bet Dagan 50250 (Israel); Halevy, Orna, E-mail: halevyo@agri.huji.ac.il [Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel)

    2010-04-01

    Halofuginone, a novel inhibitor of Smad3 phosphorylation, has been shown to inhibit muscle fibrosis and to improve cardiac and skeletal muscle functions in the mdx mouse model of Duchenne muscular dystrophy. Here, we demonstrate that halofuginone promotes the phosphorylation of Akt and mitogen-activated protein kinase (MAPK) family members in a C2 muscle cell line and in primary myoblasts derived from wild-type and mdx mice diaphragms. Halofuginone enhanced the association of phosphorylated Akt and MAPK/extracellular signal-regulated protein kinase (ERK) with the non-phosphorylated form of Smad3, accompanied by a reduction in Smad3 phosphorylation levels. This reduction was reversed by inhibitors of the phosphoinositide 3'-kinase/Akt (PI3K/Akt) and MAPK/ERK pathways, suggesting their specific role in mediating halofuginone's inhibitory effect on Smad3 phosphorylation. Halofuginone enhanced Akt, MAPK/ERK and p38 MAPK phosphorylation and inhibited Smad3 phosphorylation in myotubes, all of which are crucial for myotube fusion. In addition, halofuginone increased the association Akt and MAPK/ERK with Smad3. As a consequence, halofuginone promoted myotube fusion, as reflected by an increased percentage of C2 and mdx myotubes containing high numbers of nuclei, and this was reversed by specific inhibitors of the PI3K and MAPK/ERK pathways. Together, the data suggest a role, either direct or via inhibition of Smad3 phosphorylation, for Akt or MAPK/ERK in halofuginone-enhanced myotube fusion, a feature which is crucial to improving muscle function in muscular dystrophies.

  8. The effect of RO3201195 and a pyrazolyl ketone P38 MAPK inhibitor library on the proliferation of Werner syndrome cells.

    Science.gov (United States)

    Bagley, Mark C; Dwyer, Jessica E; Baashen, Mohammed; Dix, Matthew C; Murziani, Paola G S; Rokicki, Michal J; Kipling, David; Davis, Terence

    2016-01-21

    Microwave-assisted synthesis of the pyrazolyl ketone p38 MAPK inhibitor RO3201195 in 7 steps and 15% overall yield, and the comparison of its effect upon the proliferation of Werner Syndrome cells with a library of pyrazolyl ketones, strengthens the evidence that p38 MAPK inhibition plays a critical role in modulating premature cellular senescence in this progeroid syndrome and the reversal of accelerated ageing observed in vitro on treatment with SB203580.

  9. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian

    2012-03-06

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E 2 elevated [Ca 2+] i and increased Ca 2+ oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E 2 mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E 2 activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E 2 induces the non-genomic responses Ca 2+ release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E 2 responses. © 2012 Springer Science+Business Media, LLC.

  10. Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs

    International Nuclear Information System (INIS)

    Lopez, Soledad; Gomez, Enrique; Torres, Maria J.; Pozo, David; Fernandez, Tahia D.; Ariza, Adriana; Sanz, Maria L.; Blanca, Miguel; Mayorga, Cristobalina

    2015-01-01

    The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. - Highlights: • The cell signaling pathways related to drug-mediated DC maturation were tested. • Amoxicillin induces activation of MAPK and NF-κB in DCs from allergic patients. • The inhibition of these pathways prevents the up-regulation of DC surface molecules. • Their allostimulatory and endocytosis capacities depend on JNK and NF-κB activities. • The low involvement of p38-MAPK could be the cause of an incomplete DC maturation.

  11. Carprofen Induction of p75NTR Dependent Apoptosis via the p38 MAPK Pathway in Prostate Cancer Cells

    Science.gov (United States)

    Khwaja, Fatima S.; Quann, Emily J.; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel

    2008-01-01

    The p75NTR functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we demonstrated that treatment with R-flurbiprofen or ibuprofen induced p75NTR expression in several prostate cancer cell lines leading to p75NTR mediated decreased survival. Utilizing the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico data base of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75NTR levels and inhibition of cell survival. Prostate (PC-3, DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75NTR associated loss of survival than breast (MCF7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant negative form of p75NTR prior to carprofen treatment partially rescued cell survival demonstrating a cause and effect relationship between carprofen induction of p75NTR levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF7 and 3T3 cells. Furthermore, siRNA knockdown of the p38 MAPK protein prevented induction of p75NTR by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 minute. Expression of a dominant negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75NTR protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75NTR dependent apoptosis via the p38 MAPK pathway in prostate cancer cells. PMID:18974393

  12. The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Toward a Therapeutic Approach

    OpenAIRE

    Korf, Bruce; Ahmadian, Reza; Allanson, Judith; Aoki, Yoko; Bakker, Annette; Wright, Emma Burkitt; Denger, Brian; Elgersma, Ype; Gelb, Bruce D.; Gripp, Karen W.; Kerr, Bronwyn; Kontaridis, Maria; Lazaro, Conxi; Linardic, Corinne; Lozano, Reymundo

    2015-01-01

    "The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regard...

  13. In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

    2012-10-15

    In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

  14. Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Soledad [CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville (Spain); Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville (Spain); Gomez, Enrique [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Torres, Maria J. [Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Pozo, David [CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville (Spain); Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville (Spain); Fernandez, Tahia D.; Ariza, Adriana [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Sanz, Maria L. [Department of Allergology and Clinical Immunology, University Clinic of Navarra, Pamplona (Spain); Blanca, Miguel [Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Mayorga, Cristobalina, E-mail: lina.mayorga@ibima.eu [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain)

    2015-11-01

    The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. - Highlights: • The cell signaling pathways related to drug-mediated DC maturation were tested. • Amoxicillin induces activation of MAPK and NF-κB in DCs from allergic patients. • The inhibition of these pathways prevents the up-regulation of DC surface molecules. • Their allostimulatory and endocytosis capacities depend on JNK and NF-κB activities. • The low involvement of p38-MAPK could be the cause of an incomplete DC maturation.

  15. Three Fusarium oxysporum mitogen-activated protein kinases (MAPKs) have distinct and complementary roles in stress adaptation and cross-kingdom pathogenicity.

    Science.gov (United States)

    Segorbe, David; Di Pietro, Antonio; Pérez-Nadales, Elena; Turrà, David

    2017-09-01

    Mitogen-activated protein kinase (MAPK) cascades mediate cellular responses to environmental signals. Previous studies in the fungal pathogen Fusarium oxysporum have revealed a crucial role of Fmk1, the MAPK orthologous to Saccharomyces cerevisiae Fus3/Kss1, in vegetative hyphal fusion and plant infection. Here, we genetically dissected the individual and combined contributions of the three MAPKs Fmk1, Mpk1 and Hog1 in the regulation of development, stress response and virulence of F. oxysporum on plant and animal hosts. Mutants lacking Fmk1 or Mpk1 were affected in reactive oxygen species (ROS) homeostasis and impaired in hyphal fusion and aggregation. Loss of Mpk1 also led to increased sensitivity to cell wall and heat stress, which was exacerbated by simultaneous inactivation of Fmk1, suggesting that both MAPKs contribute to cellular adaptation to high temperature, a prerequisite for mammalian pathogens. Deletion of Hog1 caused increased sensitivity to hyperosmotic stress and resulted in partial rescue of the restricted colony growth phenotype of the mpk1Δ mutant. Infection assays on tomato plants and the invertebrate animal host Galleria mellonella revealed distinct and additive contributions of the different MAPKs to virulence. Our results indicate that positive and negative cross-talk between the three MAPK pathways regulates stress adaptation, development and virulence in the cross-kingdom pathogen F. oxysporum. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  16. Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with Trichomonas vaginalis.

    Science.gov (United States)

    Yang, Jung-Bo; Quan, Juan-Hua; Kim, Ye-Eun; Rhee, Yun-Ee; Kang, Byung-Hyun; Choi, In-Wook; Cha, Guang-Ho; Yuk, Jae-Min; Lee, Young-Ha

    2015-08-01

    Trichomonas vaginalis; induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in TNF-α production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased TNF-α production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, TNF-α production was significantly decreased compared to the control; however, TNF-α reduction patterns were different depending on the type of PI3K/MAPK inhibitors. TNF-α production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of TNF-α production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.

  17. Proteasome inhibition-induced p38 MAPK/ERK signaling regulates autophagy and apoptosis through the dual phosphorylation of glycogen synthase kinase 3β

    International Nuclear Information System (INIS)

    Choi, Cheol-Hee; Lee, Byung-Hoon; Ahn, Sang-Gun; Oh, Seon-Hee

    2012-01-01

    Highlights: ► MG132 induces the phosphorylation of GSK3β Ser9 and, to a lesser extent, of GSK3β Thr390 . ► MG132 induces dephosphorylation of p70S6K Thr389 and phosphorylation of p70S6K Thr421/Ser424 . ► Inactivation of p38 dephosphorylates GSK3β Ser9 and phosphorylates GSK3β Thr390 . ► Inactivation of p38 phosphorylates p70S6K Thr389 and increases the phosphorylation of p70S6K Thr421/Ser424 . ► Inactivation of p38 decreases autophagy and increases apoptosis induced by MG132. -- Abstract: Proteasome inhibition is a promising approach for cancer treatment; however, the underlying mechanisms involved have not been fully elucidated. Here, we show that proteasome inhibition-induced p38 mitogen-activated protein kinase regulates autophagy and apoptosis by modulating the phosphorylation status of glycogen synthase kinase 3β (GSK3β) and 70 kDa ribosomal S6 kinase (p70S6K). The treatment of MDA-MB-231 cells with MG132 induced endoplasmic reticulum stress through the induction of ATF6a, PERK phosphorylation, and CHOP, and apoptosis through the cleavage of Bax and procaspase-3. MG132 caused the phosphorylation of GSK3β at Ser 9 and, to a lesser extent, Thr 390 , the dephosphorylation of p70S6K at Thr 389 , and the phosphorylation of p70S6K at Thr 421 and Ser 424 . The specific p38 inhibitor SB203080 reduced the p-GSK3β Ser9 and autophagy through the phosphorylation of p70S6K Thr389 ; however, it augmented the levels of p-ERK, p-GSK3β Thr390 , and p-70S6K Thr421/Ser424 induced by MG132, and increased apoptotic cell death. The GSK inhibitor SB216763, but not lithium, inhibited the MG132-induced phosphorylation of p38, and the downstream signaling pathway was consistent with that in SB203580-treated cells. Taken together, our data show that proteasome inhibition regulates p38/GSK Ser9 /p70S6K Thr380 and ERK/GSK3β Thr390 /p70S6K Thr421/Ser424 kinase signaling, which is involved in cell survival and cell death.

  18. p38 MAPK mediated in compressive stress-induced chondrogenesis of rat bone marrow MSCs in 3D alginate scaffolds.

    Science.gov (United States)

    Li, Juan; Zhao, Zhihe; Yang, Jingyuan; Liu, Jun; Wang, Jun; Li, Xiaoyu; Liu, Yurong

    2009-12-01

    Mesenchymal stem cells (MSCs) are well known to have the capability to form bone and cartilage, and chondrogenesis derived from MSCs is reported to be affected by mechanical stimuli. This research was aimed to study the effects of cyclic compressive stress on the chondrogenic differentiation of rat bone marrow-derived MSCs (BMSCs) which were encapsulated in alginate scaffolds and cultured with or without chondrogenic medium, and to investigate the role of p38 MAPK phospho-relay cascade in this process. The results show that the gene expression of chondrocyte-specific markers of Col2alpha1, aggrecan, Sox9, Runx2, and Ihh was upregulated by dynamic compressive stress introduced at the 8th day of chondrogenic differentiation in vitro. The p38 MAPK was activated by chondrogenic cytokines in a slow and lagged way, but activated by cyclic compressive stimulation in a rapid and transient manner. And inhibition of p38 activity with SB203580 suppressed gene expression of chondrocyte-specific genes stimulated by chondrogenic medium and (or) cyclic compressive stress. These findings suggest that p38 MAPK signal acts as an essential mediator in the mechano-biochemical transduction and subsequent transcriptional regulation in the process of chondrogenesis.

  19. WNK1 and p38-MAPK distribution in ionocytes and accessory cells of euryhaline teleost fish implies ionoregulatory function

    Directory of Open Access Journals (Sweden)

    W. S. Marshall

    2017-07-01

    Full Text Available Ionocytes of euryhaline teleost fish secrete NaCl, under regulation by serine and threonine kinases, including with-no-lysine kinase (WNK1 and p38 mitogen-activated protein kinase (MAPK. Mummichogs (Fundulus heteroclitus L. were acclimated to freshwater (FW, full strength seawater (SW and hypersaline conditions (2SW. Immunocytochemistry of ionocytes in opercular epithelia of fish acclimated to SW and 2SW revealed that WNK1-anti-pT58 phosphoantibody localized strongly to accessory cells and was present in the cytosol of ionocytes, close to cystic fibrosis transmembrane conductance regulator (CFTR in the apical membrane and the sodium potassium 2 chloride cotransporter (NKCC in the basolateral membrane. In FW acclimated fish, WNK1 localized to a sub-apical zone, did not colocalize with apical membrane-located sodium chloride cotransporter (NCC, and typically was present in one cell of paired ionocytes and in some single ionocytes. Forskolin treatment (10 μM, 30 min increased WNK1 immunofluorescence in SW ionocytes only, while hypertonicity had little effect, compared to controls. Anti-p38-MAPK antibody localized to the cytosolic compartment. The distribution of WNK1 and p38MAPK is consistent with a proximal position in regulatory cascades, rather than directly affecting transporters. The strong staining of accessory cells by WNK1 phosphoantibody infers an osmoregulatory function for WNK.

  20. The participation of NMDA receptors, PKC, and MAPK in the formation of memory following operant conditioning in Lymnaea

    Directory of Open Access Journals (Sweden)

    Rosenegger David

    2010-08-01

    Full Text Available Abstract Background Memory is the ability to store, retain, and later retrieve information that has been learned. Intermediate term memory (ITM that persists for up to 3 h requires new protein synthesis. Long term memory (LTM that persists for at least 24 h requires: DNA transcription, RNA translation, and the trafficking of newly synthesized proteins. It has been shown in a number of different model systems that NMDA receptors, protein kinase C (PKC and mitogen activated protein kinase (MAPK are all involved in the memory formation process. Results Here we show that snails trained in control conditions are capable of forming, depending on the training procedure used, either ITM or LTM. However, blockage of NMDA receptors (MK 801, inhibition of PKC (GF109203X hydrochloride and MAPK activity (UO126 prevent the formation of both ITM and LTM. Conclusions The injection of either U0126 or GF109203X, which inhibit MAPK and PKC activity respectively, 1 hour prior to training results in the inhibition of both ITM and LTM formation. We further found that NMDA receptor activity was necessary in order for both ITM and LTM formation.

  1. Effect of Glucagon-like Peptide 2 on Tight Junction in Jejunal Epithelium of Weaned Pigs though MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Changsong Yu

    2014-05-01

    Full Text Available The glucagon-like peptide 2 (GLP-2 that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets’ intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK signaling pathway in piglets’ intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco’s modified Eagle’s medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1, occludin and claudin-1 were increased (p<0.05. U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05. In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs’ jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.

  2. Inhibition of CD147 expression promotes chemosensitivity in HNSCC cells by deactivating MAPK/ERK signaling pathway.

    Science.gov (United States)

    Ma, Chao; Wang, Jianqi; Fan, Longkun; Guo, Yanjun

    2017-02-01

    Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. CD147, a transmembrane glycoprotein, has been reported to be correlated with cancer progression, metastasis, and chemoresistance in various cancers. In this study, we aimed to investigate the mechanism of CD147 in regulating drug resistance in HNSCC cells. qRT-PCR were used to evaluated the expression of CD147 in 57 HNSCC tumorous tissues and 2 cell lines. Increased expression of CD147 was found in most HNSCC samples, and the expression level of CD147 was correlated with multidrug resistance. CD147 RNA silencing decreased the chemoresistance of HNSCC cells by deactivating MAPK/ERK signaling pathway. Further investigation revealed that either rescue expression of CD147 or treatment of MAPK/ERK activator phorbol 12-myristate 13-acetate (PMA) in CD147 knockdown CRC cell line attenuated the decreased chemoresistance in CD147 knockdown cells. Taken together, our results suggest that CD147 promotes chemoresistance by activating MAPK/ERK signaling pathway in HNSCC. Copyright © 2017. Published by Elsevier Inc.

  3. Inhibition of p38 MAPK enhances ABT-737-induced cell death in melanoma cell lines: novel regulation of PUMA.

    Science.gov (United States)

    Keuling, Angela M; Andrew, Susan E; Tron, Victor A

    2010-06-01

    The mitogen-activated protein kinase (MAPK) pathway is constitutively activated in the majority of melanomas, promoting cell survival, proliferation and migration. In addition, anti-apoptotic Bcl-2 family proteins Mcl-1, Bcl-xL and Bcl-2 are frequently overexpressed, contributing to melanoma's well-documented chemoresistance. Recently, it was reported that the combination of MAPK pathway inhibition by specific MEK inhibitors and Bcl-2 family inhibition by BH3-mimetic ABT-737 synergistically induces apoptotic cell death in melanoma cell lines. Here we provide the first evidence that inhibition of another key MAPK, p38, synergistically induces apoptosis in melanoma cells in combination with ABT-737. We also provide novel mechanistic data demonstrating that inhibition of p38 increases expression of pro-apoptotic Bcl-2 protein PUMA. Furthermore, we demonstrate that PUMA can be cleaved by a caspase-dependent mechanism during apoptosis and identify what appears to be the PUMA cleavage product. Thus, our findings suggest that the combination of ABT-737 and inhibition of p38 is a promising, new treatment strategy that acts through a novel PUMA-dependent mechanism.

  4. JWA deficiency suppresses dimethylbenz[a]anthracene-phorbol ester induced skin papillomas via inactivation of MAPK pathway in mice.

    Directory of Open Access Journals (Sweden)

    Zhenghua Gong

    Full Text Available Our previous studies indicated that JWA plays an important role in DNA damage repair, cell migration, and regulation of MAPKs. In this study, we investigated the role of JWA in chemical carcinogenesis using conditional JWA knockout (JWA(Δ2/Δ2 mice and two-stage model of skin carcinogenesis. Our results indicated that JWA(Δ2/Δ2 mice were resistant to the development of skin papillomas initiated by 7, 12-dimethylbenz(aanthracene (DMBA followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA. In JWA(Δ2/Δ2 mice, the induction of papilloma was delayed, and the tumor number and size were reduced. In primary keratinocytes from JWA(Δ2/Δ2 mice, DMBA exposure induced more intensive DNA damage, while TPA-promoted cell proliferation was reduced. The further mechanistic studies showed that JWA deficiency blocked TPA-induced activation of MAPKs and its downstream transcription factor Elk1 both in vitro and in vivo. JWA(Δ2/Δ2 mice are resistance to tumorigenesis induced by DMBA/TPA probably through inhibition of transcription factor Elk1 via MAPKs. These results highlight the importance of JWA in skin homeostasis and in the process of skin tumor development.

  5. Blockage of NOX2/MAPK/NF-κB Pathway Protects Photoreceptors against Glucose Deprivation-Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Bin Fan

    2017-01-01

    Full Text Available Acute energy failure is one of the critical factors contributing to the pathogenic mechanisms of retinal ischemia. Our previous study demonstrated that glucose deprivation can lead to a caspase-dependent cell death of photoreceptors. The aim of this study was to decipher the upstream signal pathway in glucose deprivation- (GD- induced cell death. We mimicked acute energy failure by using glucose deprivation in photoreceptor cells (661W cells. GD-induced oxidative stress was evaluated by measuring ROS with the DCFH-DA assay and HO-1 expression by Western blot analysis. The activation of NOX2/MAPK/NF-κB signal was assessed by Western blot and immunohistochemical assays. The roles of these signals in GD-induced cell death were measured by using their specific inhibitors. Inhibition of Rac-1 and NOX2 suppressed GD-induced oxidative stress and protected photoreceptors against GD-induced cell death. NOX2 was an upstream signal in the caspase-dependent cell death cascade, yet the downstream MAPK pathways were activated and blocking MAPK signals rescued 661W cells from GD-induced death. In addition, GD caused the activation of NF-κB signal and inhibiting NF-κB significantly protected 661W cells. These observations may provide insights for treating retinal ischemic diseases and protecting retinal neurons from ischemia-induced cell death.

  6. Culture medium, gas atmosphere and MAPK inhibition affect regulation of RNA-binding protein targets during mouse preimplantation development.

    Science.gov (United States)

    Calder, Michele D; Watson, Patricia H; Watson, Andrew J

    2011-11-01

    During oogenesis, mammalian oocytes accumulate maternal mRNAs that support the embryo until embryonic genome activation. RNA-binding proteins (RBP) may regulate the stability and turnover of maternal and embryonic mRNAs. We hypothesised that varying embryo culture conditions, such as culture medium, oxygen tension and MAPK inhibition, affects regulation of RBPs and their targets during preimplantation development. STAU1, ELAVL1, KHSRP and ZFP36 proteins and mRNAs were detected throughout mouse preimplantation development, whereas Elavl2 mRNA decreased after the two-cell stage. Potential target mRNAs of RBP regulation, Gclc, Slc2a1 and Slc7a1 were detected during mouse preimplantation development. Gclc mRNA was significantly elevated in embryos cultured in Whitten's medium compared with embryos cultured in KSOMaa, and Gclc mRNA was elevated under high-oxygen conditions. Inhibition of the p38 MAPK pathway reduced Slc7a1 mRNA expression while inhibition of ERK increased Slc2a1 mRNA expression. The half-lives of the potential RBP mRNA targets are not regulated in parallel; Slc2a1 mRNA displayed the longest half-life. Our results indicate that mRNAs and proteins encoding five RBPs are present during preimplantation development and more importantly, demonstrate that expression of RBP target mRNAs are regulated by culture medium, gas atmosphere and MAPK pathways.

  7. Klotho Protects Dopaminergic Neuron Oxidant-Induced Degeneration by Modulating ASK1 and p38 MAPK Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Reynolds K Brobey

    Full Text Available Klotho transgenic mice exhibit resistance to oxidative stress as measured by their urinal levels of 8-hydroxy-2-deoxyguanosine, albeit this anti-oxidant defense mechanism has not been locally investigated in the brain. Here, we tested the hypothesis that the reactive oxygen species (ROS-sensitive apoptosis signal-regulating kinase 1 (ASK1/p38 MAPK pathway regulates stress levels in the brain of these mice and showed that: 1 the ratio of free ASK1 to thioredoxin (Trx-bound ASK1 is relatively lower in the transgenic brain whereas the reverse is true for the Klotho knockout mice; 2 the reduced p38 activation level in the transgene corresponds to higher level of ASK1-bound Trx, while the KO mice showed elevated p38 activation and lower level of-bound Trx; and 3 that 14-3-3ζ is hyper phosphorylated (Ser-58 in the transgene which correlated with increased monomer forms. In addition, we evaluated the in vivo robustness of the protection by challenging the brains of Klotho transgenic mice with a neurotoxin, MPTP and analyzed for residual neuron numbers and integrity in the substantia nigra pars compacta. Our results show that Klotho overexpression significantly protects dopaminergic neurons against oxidative damage, partly by modulating p38 MAPK activation level. Our data highlight the importance of ASK1/p38 MAPK pathway in the brain and identify Klotho as a possible anti-oxidant effector.

  8. Synthesis of the highly selective p38 MAPK inhibitor UR-13756 for possible therapeutic use in Werner syndrome.

    Science.gov (United States)

    Bagley, Mark C; Davis, Terence; Rokicki, Michal J; Widdowson, Caroline S; Kipling, David

    2010-02-01

    UR-13756 is a potent and selective p38 mitogen-activated protein kinase (MAPK) inhibitor, reported to have good bioavailability and pharmacokinetic properties and, thus, is of potential use in the treatment of accelerated aging in Werner syndrome. Irradiation of 2-chloroacrylonitrile and methylhydrazine in ethanol at 100 °C gives 1-methyl-3-aminopyrazole, which reacts with 4-fluorobenzaldehyde and a ketone, obtained by Claisen condensation of 4-picoline, in a Hantzsch-type 3-component hereocyclocondensation, to give the pyrazolopyridine UR-13756. UR-13756 shows p38 MAPK inhibitory activity in human telomerase reverse transcriptase-immortalized HCA2 dermal fibroblasts, with an IC(50) of 80 nm, as shown by ELISA, is 100% efficacious for up to 24 h at 1.0 μm and displays excellent kinase selectivity over the related stress-activated c-Jun kinases. In addition, UR-13756 is an effective p38 inhibitor at 1.0 μm in Werner syndrome cells, as shown by immunoblot. The convergent synthesis of UR-13756 is realized using microwave dielectric heating and provides a highly selective inhibitor that shows excellent selectivity for p38 MAPK over c-Jun N-terminal kinase.