MRI of meniscal bucket-handle tears

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Magee, T.H.; Hinson, G.W. [Menorah Medical Center, Overland Park, KS (United States). Dept. of Radiology

1998-09-01

A meniscal bucket-handle tear is a tear with an attached fragment displaced from the meniscus of the knee joint. Low sensitivity of MRI for detection of bucket-handle tears (64% as compared with arthroscopy) has been reported previously. We report increased sensitivity for detecting bucket-handle tears with the use of coronal short tau inversion recovery (STIR) images. Results. By using four criteria for diagnosis of meniscal bucket-handle tears, our overall sensitivity compared with arthroscopy was 93% (28 of 30 meniscal bucket-handle tears seen at arthroscopy were detected by MRI). The meniscal fragment was well visualized in all 28 cases on coronal STIR images. The double posterior cruciate ligament sign was seen in 8 of 30 cases, the flipped meniscus was seen in 10 of 30 cases and a fragment in the intercondylar notch was seen in 18 of 30 cases. (orig.)

Advances and Prospects in Tissue-Engineered Meniscal Scaffolds for Meniscus Regeneration

Directory of Open Access Journals (Sweden)

Weimin Guo

2015-01-01

Full Text Available The meniscus plays a crucial role in maintaining knee joint homoeostasis. Meniscal lesions are relatively common in the knee joint and are typically categorized into various types. However, it is difficult for inner avascular meniscal lesions to self-heal. Untreated meniscal lesions lead to meniscal extrusions in the long-term and gradually trigger the development of knee osteoarthritis (OA. The relationship between meniscal lesions and knee OA is complex. Partial meniscectomy, which is the primary method to treat a meniscal injury, only relieves short-term pain; however, it does not prevent the development of knee OA. Similarly, other current therapeutic strategies have intrinsic limitations in clinical practice. Tissue engineering technology will probably address this challenge by reconstructing a meniscus possessing an integrated configuration with competent biomechanical capacity. This review describes normal structure and biomechanical characteristics of the meniscus, discusses the relationship between meniscal lesions and knee OA, and summarizes the classifications and corresponding treatment strategies for meniscal lesions to understand meniscal regeneration from physiological and pathological perspectives. Last, we present current advances in meniscal scaffolds and provide a number of prospects that will potentially benefit the development of meniscal regeneration methods.

MR imaging of meniscal tears: correlation with history of trauma

International Nuclear Information System (INIS)

Choi, Jong Cheul; Yang, Seoung Oh; Choi, Sun Seob; Son, Seok Hyun; Lee, Yung Il; Chung, Duck Hwan; Kim, Kyung Taek; Sohn, Sung Keun; Lee, Jung Yoon

1994-01-01

The medial meniscus is injured much more than the lateral meniscus. Because the medial meniscus is much larger in diameter, is thinner in its periphery and narrower in body than the lateral meniscus, and dose not attach to either cruciate ligament. We evaluated correlations with sites of tear and history of trauma. We reviewed retrospectively in 43 patients with meniscal tears on MR(51 cases) and correlated them with history of trauma. The most common site of injury was the posterior horn of the medial meniscuc(32/51), but high incidence of lateral meniscal tear compared with previous reports was seen. In the cases which had history of trauma, the posterior horn of medial meniscus was most commonly injured(26/34) and 5 meniscal tears were combined with meniscal tear in the other site. The tear in the anterior horn of the medial meniscus was seen only in a patient which had history of trauma and combined with meniscal tear in the other site. But in the meniscal tears without definite history of trauma, the incidence of meniscal tear was different from the meniscal tear with history of trauma. The incidence of lateral meniscal tear(11/17) was higher than medial meniscal tear and the posterior horn of lateral meniscus was commonly injured. We concluded that the medial meniscus was commonly injured, especially posterior horn, but in the cases which had no definite history of trauma, the lateral meniscus was commonly injured. An awareness of prevalent site of meniscal injuries may be helpful in the diagnostic interpretation of MR imaging of knee

Utility of three-dimensional method for diagnosing meniscal lesions

International Nuclear Information System (INIS)

Ohshima, Suguru; Nomura, Kazutoshi; Hirano, Mako; Hashimoto, Noburo; Fukumoto, Tetsuya; Katahira, Kazuhiro

1998-01-01

MRI of the knee is a useful method for diagnosing meniscal tears. Although the spin echo method is usually used for diagnosing meniscal tears, we examined the utility of thin slice scan with the three-dimensional method. We reviewed 70 menisci in which arthroscopic findings were confirmed. In this series, sensitivity was 90.9% for medial meniscal injuries and 68.8% for lateral meniscal injuries. There were 3 meniscal tears in which we could not detect tears on preoperative MRI. We could find tears in two of these cases when re-evaluated using the same MRI. In conclusion, we can get the same diagnostic rate with the three-dimensional method compared with the spin echo method. Scan time of the three-dimensional method is 3 minutes, on the other hand that of spin echo method in 17 minutes. This slice scan with three-dimensional method is useful for screening meniscal injuries before arthroscopy. (author)

Meniscal transplantation: still experimental surgery? A review.

Science.gov (United States)

Moens, K; Dhollander, A; Moens, P; Verdonk, K; Verdonk, R; Almqvist, K F; Victor, J

2014-09-01

The objective of this review is to give a state of affairs of meniscal transplantation, with the accent on preservation and surgical techniques. All articles were selected by performing a search on the literature by using relevant keywords. The most relevant articles were selected with close attention to the publication date. When a meniscal tear is diagnosed, suture can be an option in the vascular zone, whereas the more frequently affected avascular zone heals poorly. A meniscectomy however is not without consequences, wherefore meniscal transplantation can be seen as a therapeutic option for pain reduction and improvement of function when the meniscus is lost. The meniscal scaffold, allograft and autograft can be currently withheld as possible grafts, where the meniscal scaffolds hold great promise as an alternative to the allograft. Various fixation techniques are therefore developed, where viable, deep frozen as well as cryopreservated allografts seem to give the most promising short term results. The transplantation can be performed using an open as well as an arthroscopic technique, using soft tissue fixation, bone plugs or blocks. De primacy of one technique can't be proven. In general meniscal transplantation can be considered as an acceptable procedure. Since the outcomes of different studies are difficult to compare, an attempt should be made to limit new studies to the comparison of one aspect. We can conclude that larger, more comparative randomised controlled long-term studies are necessary to resolve which techniques can give the best long-term results.

Diagnostic value of self-reported mechanical symptoms for diagnosing large meniscal tears in patients aged 40 years or older with meniscal tears

DEFF Research Database (Denmark)

Pihl, Kenneth; Englund, Martin; Lohmander, Stefan

2017-01-01

Purpose: Meniscal tears, which are longitudinal-vertical tears (e.g. bucket-handle tears) and/or involve all three meniscal sub regions (anterior horn, body and posterior horn), are typically large and assumed to cause patient perceived mechanical knee symptoms (knee grinding or clicking and knee...... catching or locking). However, whether the presence of such mechanical symptoms is useful for diagnosing these forms of meniscus tears is unknown. Therefore, we investigated the diagnostic values of having mechanical symptoms in diagnosing a bucket-handle tear and/or a tear involving all three meniscal sub...... regions in middle-aged and older patients undergoing arthroscopic meniscal surgery. Methods: This study is a secondary analysis of Pihl et al. OARSI 2017. The study included patients aged 40 years or older undergoing surgery for a meniscal tear from Knee Arthroscopy Cohort Southern Denmark (KACS...

Meniscal shear stress for punching.

Science.gov (United States)

Tuijthof, Gabrielle J M; Meulman, Hubert N; Herder, Just L; van Dijk, C Niek

2009-01-01

Experimental determination of the shear stress for punching meniscal tissue. Meniscectomy (surgical treatment of a lesion of one of the menisci) is the most frequently performed arthroscopic procedure. The performance of a meniscectomy is not optimal with the currently available instruments. To design new instruments, the punching force of meniscal tissue is an important parameter. Quantitative data are unavailable. The meniscal punching process was simulated by pushing a rod through meniscal tissue at constant speed. Three punching rods were tested: a solid rod of Oslash; 3.00 mm, and two hollow tubes (Oslash; 3.00-2.60 mm) with sharpened cutting edges of 0.15 mm and 0.125 mm thick, respectively. Nineteen menisci acquired from 10 human cadaveric knee joints were punched (30 tests). The force and displacement were recorded from which the maximum shear stress was determined (average added with three times the standard deviation). The maximum shear stress for the solid rod was determined at 10.2 N/mm2. This rod required a significantly lower punch force in comparison with the hollow tube having a 0.15 mm cutting edge (plt;0.01). The maximum shear stress for punching can be applied to design instruments, and virtual reality training environments. This type of experiment is suitable to form a database with material properties of human tissue similar to databases for the manufacturing industry.

Role of MRI in predicting meniscal tear reparability

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Felisaz, Paolo Florent [Universita degli Studi di Pavia, Pavia (Italy); Fondazione IRCCS Policlinico San Matteo, Istituto di Radiologia, Pavia (Italy); Alessandrino, Francesco; Perelli, Simone [Universita degli Studi di Pavia, Pavia (Italy); Zanon, Giacomo; Benazzo, Francesco [Fondazione IRCCS Policlinico San Matteo, Clinica Ortopedica e Traumatologica, Pavia (Italy); Calliada, Fabrizio; Sammarchi, Luigi [Fondazione IRCCS Policlinico San Matteo Radiologia, Diagnostica per Immagini-Istituto di Radiologia, Pavia (Italy)

2017-10-15

To elucidate the role of MRI in predicting meniscal tear reparability according to tear type and location in relation to vascular zones. In this retrospective study, two readers evaluated 79 pre-surgical MRIs of meniscal tears arthroscopically treated with meniscectomy or meniscal repair. Tears were classified according to type into vertical, horizontal, radial, complex, flaps and bucket handle and were considered reparable if the distance measured from the tear to the menisco-capsular junction was less than or equal to 5 mm. Predictions were compared with the surgical procedure performed in arthroscopy. We assessed the diagnostic performance of MRI, agreement between MRI and arthroscopy, and interrater agreement. Then, we conducted an ROC analysis on the distances measured by the first reader and built a multivariate logistic regression model. MRI had a sensitivity, specificity, PPV, NPV and accuracy, respectively, of 85%, 79%, 86%, 76% and 83% in predicting meniscal tear reparability. Correct predictions for the specific tear pattern were 76% for vertical, 84% for horizontal, 88% for radial, 86% for complex, 84% for flaps and 86% for bucket handle. Agreement between the two readers' predictions and arthroscopy was good (k = 0.65 and 0.61, respectively). Inter-rater agreement was almost excellent (k = 0.79). The ROC analysis revealed sensitivity and specificity of 73% and 83% with a cutoff value of <4 mm (p < 0.001). Anterior cruciate ligament injury and medial meniscal tear increased the likelihood of meniscal tear reparability. MRI can be a reliable and accurate tool to predict the reparability of meniscal tears, with higher prediction rates for bucket-handle tears. (orig.)

Arthroscopic Meniscal Allograft Transplantation With Soft-Tissue Fixation Through Bone Tunnels.

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Spalding, Tim; Parkinson, Ben; Smith, Nick A; Verdonk, Peter

2015-10-01

Meniscal allograft transplantation improves clinical outcomes for patients with symptomatic meniscus-deficient knees. We describe an established arthroscopic technique for meniscal allograft transplantation without the need for bone fixation of the meniscal horns. After preparation of the meniscal bed, the meniscus is parachuted into the knee through a silicone cannula and the meniscal horns are fixed with sutures through bone tunnels. The body of the meniscus is then fixed with a combination of all-inside and inside-out sutures. This technique is reliable and reproducible and has clinical outcomes comparable with those of bone plug fixation techniques.

Posterior horn medial meniscal root tear: the prequel

Energy Technology Data Exchange (ETDEWEB)

Umans, H. [Albert Einstein College of Medicine, Bronx, NY (United States); Lenox Hill Radiology and Imaging Associates, New York, NY (United States); Morrison, W. [Thomas Jefferson University Hospital, Philadelphia, PA (United States); DiFelice, G.S. [Hospital for Special Surgery, New York, NY (United States); Vaidya, N. [Crystal Run Healthcare, Middletown, NY (United States); Winalski, C.S. [Cleveland Clinic, Imaging Institute, Department of Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States)

2014-06-15

To determine whether subarticular marrow changes deep to the posterior horn medial meniscal root anchor might predict subsequent medial meniscal root tear. Fifteen patients with MR-diagnosed posterior horn medial meniscal root (PHMMR) tear and a knee MRI antecedent to the tear were identified at three imaging centers over a 7-year period. The pre- and post-tear MR images were evaluated for marrow signal changes deep to the root anchor, meniscal root signal intensity, medial compartment articular cartilage thinning, and meniscal body extrusion. Images of 29 age- and gender-matched individuals with two MRIs of the same knee were reviewed as a control group. MRI in 11 of 15 (73 %) cases with subsequent PHMMR tear demonstrated linear subcortical marrow edema deep to the meniscal root anchor on the antecedent MRI compared to only 1 of 29 (3 %) non-tear controls (p < 0.0001). The abnormal signal resolved on post-tear MRI in all but two patients. Cyst-like changes deep to the PHMMR were present on initial MRI in three of 15 (23 %) cases and three of 29 (10 %) controls, persisting in all but one case on follow-up imaging. The PHMMR was gray on the initial MRI in seven of 15 (47 %) of cases that developed tears compared to four of 29 (14 %) controls (p < 0.0001). There was medial meniscal extrusion (MME) prior to tear in two of 15 (13 %) patients and in ten of 15 (67 %) patients after PHMMR failure. In the control group, MME was present in one (3 %) and three (10 %) of 29 subjects on the initial and follow-up MRIs, respectively. Articular cartilage loss was noted in two of 15 (15 %) cases before tear and nine of 15 (69 %) on follow-up imaging, as compared to one (3 %) and four (14 %) of 29 subjects in the control group. Subcortical marrow edema deep to the PHMMR may result from abnormal stresses and thus be a harbinger of meniscal root failure. This hypothesis is supported by resolution of these marrow signal changes after root tear. Following tear, extrusion of the

The potential of optical coherence tomography for diagnosing meniscal pathology

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Hang-Yin Ling, Carrie; Pozzi, Antonio; Thieman, Kelley M.; Tonks, Catherine A.; Guo, Shuguang; Xie, Huikai; Horodyski, MaryBeth

2010-04-01

Meniscal tears are often associated with anterior cruciate ligament (ACL) injury and may lead to pain and discomfort in humans. Maximal preservation of meniscal tissue is highly desirable to mitigate the progression of osteoarthritis. Guidelines of which meniscal tears are amenable to repair and what part of damaged tissues should be removed are elusive and lacking consensus. Images of microstructural changes in meniscus would potentially guide the surgeons to manage the meniscal tears better, but the resolution of current diagnostic techniques is limited for this application. In this study, we demonstrated the feasibility of using optical coherence tomography (OCT) for the diagnosis of meniscal pathology. Torn medial menisci were collected from dogs with ACL insufficiency. The torn meniscus was divided into three tissue samples and scanned by OCT and scanning electron microscopy (SEM). OCT and SEM images of torn menisci were compared. Each sample was evaluated for gross and microstructural abnormalities and reduction or loss of birefringence from the OCT images. The abnormalities detected with OCT were described for each type of tear. OCT holds promise in non-destructive and fast assessment of microstructural changes and tissue birefringence of meniscal tears. Future development of intraoperative OCT may help surgeons in the decision making of meniscal treatment.

The potential of optical coherence tomography for diagnosing meniscal pathology

International Nuclear Information System (INIS)

Ling, Carrie Hang-Yin; Horodyski, MaryBeth; Pozzi, Antonio; Thieman, Kelley M; Tonks, Catherine A; Guo, Shuguang; Xie, Huikai

2010-01-01

Meniscal tears are often associated with anterior cruciate ligament (ACL) injury and may lead to pain and discomfort in humans. Maximal preservation of meniscal tissue is highly desirable to mitigate the progression of osteoarthritis. Guidelines of which meniscal tears are amenable to repair and what part of damaged tissues should be removed are elusive and lacking consensus. Images of microstructural changes in meniscus would potentially guide the surgeons to manage the meniscal tears better, but the resolution of current diagnostic techniques is limited for this application. In this study, we demonstrated the feasibility of using optical coherence tomography (OCT) for the diagnosis of meniscal pathology. Torn medial menisci were collected from dogs with ACL insufficiency. The torn meniscus was divided into three tissue samples and scanned by OCT and scanning electron microscopy (SEM). OCT and SEM images of torn menisci were compared. Each sample was evaluated for gross and microstructural abnormalities and reduction or loss of birefringence from the OCT images. The abnormalities detected with OCT were described for each type of tear. OCT holds promise in non-destructive and fast assessment of microstructural changes and tissue birefringence of meniscal tears. Future development of intraoperative OCT may help surgeons in the decision making of meniscal treatment

Study protocol for a randomised controlled trial of meniscal surgery compared with exercise and patient education for treatment of meniscal tears in young adults

DEFF Research Database (Denmark)

Skou, Soren Thorgaard; Lind, Martin; Holmich, Per

2017-01-01

INTRODUCTION: Arthroscopic surgery is a very common orthopaedic procedure. While several trials have investigated the effect of knee arthroscopy for middle-aged and older patients with meniscal tears, there is a paucity of trials comparing meniscal surgery with non-surgical treatment for younger...... adults. The aim of this randomised controlled trial (RCT) is to investigate if early arthroscopic surgery is superior to exercise therapy and education, with the option of later surgery if needed, in improving pain, function and quality of life in younger adults with meniscal tears. METHODS AND ANALYSIS......: This is a protocol for a multicentre, parallel-group RCT conducted at six hospitals across all five healthcare regions in Denmark. 140 patients aged 18-40 years with a clinical history and symptoms consistent with a meniscal tear, verified on MRI, found eligible for meniscal surgery by an orthopaedic surgeon...

Meniscal tears, repairs and replacement: their relevance to osteoarthritis of the knee.

Science.gov (United States)

McDermott, Ian

2011-04-01

The menisci of the knee are important load sharers and shock absorbers in the joint. Meniscal tears are common, and whenever possible meniscal tears should be surgically repaired. Meniscectomy leads to a significant increased risk of osteoarthritis, and various options now exist for replacing missing menisci, including the use of meniscal scaffolds or the replacement of the entire meniscus by meniscal allograft transplantation. The field of meniscal surgery continues to develop apace, and the future may lie in growing new menisci by tissue engineering techniques.

Meniscal Allograft Transplantation: State of the Art.

Science.gov (United States)

Trentacosta, Natasha; Graham, William C; Gersoff, Wayne K

2016-06-01

Meniscal allograft transplantation has evolved over the years to provide a state-of-the-art technique for the sports medicine surgeon to utilize in preserving contact mechanics and function of the knee in irreparable meniscal pathology. However, this procedure continues to spark considerable debate on proper tissue processing techniques, acceptable indications, methods of implantation, and potential long-term outcomes.

Use of porous polyurethanes for meniscal reconstruction and meniscal prostheses

NARCIS (Netherlands)

deGroot, JH; deVrijer, R; Pennings, AJ; Veth, RPH; Jansen, HWB

In the past, porous materials made of an aromatic polyurethane (PU) were successfully used for meniscal reconstruction in dogs. Since aromatic PUs yield very toxic fragments upon degradation, a linear PU was synthesized by curing a poly(epsilon-caprolactone) and 1,4-trans-cyclohexane diisocyanate I

Chondral Injuries and Irreparable Meniscal Tears Among Adolescents With Anterior Cruciate Ligament or Meniscal Tears Are More Common in Patients With Public Insurance.

Science.gov (United States)

Williams, Ariel A; Mancini, Nickolas S; Solomito, Matthew J; Nissen, Carl W; Milewski, Matthew D

2017-07-01

Access to health care services is a critical component of health care reform and may differ among patients with different types of insurance. Hypothesis/Purpose: The purpose was to compare adolescents with private and public insurance undergoing surgery for anterior cruciate ligament (ACL) and/or meniscal tears. We hypothesized that patients with public insurance would have a delayed presentation from the time of injury and therefore would have a higher incidence of chondral injuries and irreparable meniscal tears and lower preoperative International Knee Documentation Committee (IKDC) scores than patients with private insurance. Cross-sectional study; Level of evidence, 3. This was a retrospective study of patients under 21 years of age undergoing ACL reconstruction and/or meniscal repair or debridement from January 2013 to March 2016 at a single pediatric sports medicine center. Patients were identified by a search of Current Procedural Terminology (CPT) codes. A chart review was performed for insurance type; preoperative diagnosis; date of injury, initial office visit, and surgery; preoperative IKDC score; intraoperative findings; and procedures. The study group consisted of 119 patients (mean age, 15.0 ± 1.7 years). Forty-one percent of patients had private insurance, while 59% had public insurance. There were 27 patients with isolated meniscal tears, 59 with combined meniscal and ACL tears, and 33 with isolated ACL tears. The mean time from injury to presentation was 56 days (range, 0-457 days) in patients with private insurance and 136 days (range, 0-1120 days) in patients with public insurance ( P = .02). Surgery occurred, on average, 35 days after the initial office visit in both groups. The mean preoperative IKDC score was 53 in both groups. Patients with meniscal tears with public insurance were more likely to require meniscal debridement than patients with private insurance (risk ratio [RR], 2.3; 95% CI, 1.7-3.1; P = .02). Patients with public insurance

MRI diagnosis of meniscal tears

International Nuclear Information System (INIS)

Kuga, Naoyuki; Oh, Toshihiro

1996-01-01

We studied the accuracy of magnetic resonance imaging (MRI) of the knee in fifty-six patients who were also examined arthroscopically. The accuracy, sensitivity, and specificity were 96%, 100%, and 95% for medial meniscal tears, and 91%, 67%, and 100% for lateral meniscal tears respectively. Two MRIs of the medial meniscus were false-positives. These MRI findings were both meniscocapsular separation of the medial meniscus, but the arthroscopic findings were normal. One case was an ACL injury and the other PCL and MCL injury. Hemorrhage and edema of the medial capsule caused by valgus stress at injury may look like a meniscal pseudo-tear on MRI. Five MRIs of the lateral meniscus were false-negatives. All menisci showed normal signal and shape on MRI but traumatic and stable tears of the lateral meniscus were identified arthroscopically. All were associated with ACL tears and lateral condylar bone bruise. The traumatic and stable tear of the meniscus tended to be overlooked on MRI because a meniscus without degeneration shows a normal signal. (author)

Surgical interventions for meniscal tears: a closer look at the evidence

NARCIS (Netherlands)

Mutsaerts, Eduard L. A. R.; van Eck, Carola F.; van de Graaf, Victor A.; Doornberg, Job N.; van den Bekerom, Michel P. J.

2016-01-01

The aim of the present study was to compare the outcomes of various surgical treatments for meniscal injuries including (1) total and partial meniscectomy; (2) meniscectomy and meniscal repair; (3) meniscectomy and meniscal transplantation; (4) open and arthroscopic meniscectomy and (5) various

Detection of meniscal injuries using MR imaging

International Nuclear Information System (INIS)

Lotysch, M.; Mink, J.H.; Levy, T.; Schwartz, A.; Crues, J.V. III.

1986-01-01

Eighty-six knees studied by MR imaging were treated operatively and the surgical-radiologic conditions were reviewed using the following grading system of meniscal signal: grade 1, globular signal within the meniscus that does not involve an articular margin; grade 2, linear signal within the meniscus that does not extend to an articular surface; grade 3, linear or globular signal extending to an articular surface. This grading system was applied to evaluate 86 knees (172 menisci). Eleven menisci had been treated operatively at an earlier period and were excluded. Of 92 grade 1 or 2 menisci, 88 were normal at surgery. Of 69 grade 3 minisci, lesions were associated with meniscal tears in 68 at surgery. MR imaging is an accurate method of evaluating meniscal surgery

Surgical interventions for meniscal tears: a closer look at the evidence.

Science.gov (United States)

Mutsaerts, Eduard L A R; van Eck, Carola F; van de Graaf, Victor A; Doornberg, Job N; van den Bekerom, Michel P J

2016-03-01

The aim of the present study was to compare the outcomes of various surgical treatments for meniscal injuries including (1) total and partial meniscectomy; (2) meniscectomy and meniscal repair; (3) meniscectomy and meniscal transplantation; (4) open and arthroscopic meniscectomy and (5) various different repair techniques. The Bone, Joint and Muscle Trauma Group Register, Cochrane Database, MEDLINE, EMBASE and CINAHL were searched for all (quasi) randomized controlled clinical trials comparing various surgical techniques for meniscal injuries. Primary outcomes of interest included patient-reported outcomes scores, return to pre-injury activity level, level of sports participation and persistence of pain using the visual analogue score. Where possible, data were pooled and a meta-analysis was performed. A total of nine studies were included, involving a combined 904 subjects, 330 patients underwent a meniscal repair, 402 meniscectomy and 160 a collagen meniscal implant. The only surgical treatments that were compared in homogeneous fashion across more than one study were the arrow and inside-out technique, which showed no difference for re-tear or complication rate. Strong evidence-based recommendations regarding the other surgical treatments that were compared could not be made. This meta-analysis illustrates the lack of level I evidence to guide the surgical management of meniscal tears. Level I meta-analysis.

Inferomedial displacement of the meniscal free fragment: MR findings

International Nuclear Information System (INIS)

Sorrentino, Fortunato; Iovane, Angelo; Nicosia, Antonio; Candela, Fabrizio; Midiri, Massimo; De Maria, Marcello

2005-01-01

Purpose. To define the accuracy of Magnetic Resonance (MR) in the diagnosis of inferomedial displacement of the meniscal fragments. Materials and methods. The MR examinations of the knee performed between December 2002 and April 2004 on 676 patients (mean age 32 years) with knee trauma and subsequently subjected to arthroscopy were retrospectively reviewed to assess the presence of bucket-handle meniscal tear and inferomedial displacement of the meniscal free fragment. The MR examinations were performed using a superconductive 0.5 T MR unit with a transmitting/receiving coil dedicated for the extremities. The MR images were acquired with SE T1 and GE T2 sequences in the sagittal, coronal and axial planes with 3 mm thickness and 1 mm gap. The images were independently reviewed by two authors blinded to the arthroscopy findings. In case of disagreement, a third author, unaware of the arthroscopic findings, gave his judgment. Results. On MR images a bucket-handle meniscal tear was identified in 54/676 patients. In 6 out of 54 patients, an inferomedial meniscal fragment displacement of the medical meniscus with associated inflammatory synovial reaction around the distal insertion of the medial homolateral collateral ligament was detected. All cases were confirmed by arthroscopy and no statistical differences between the two authors were observed. Conclusions. MR allows the detection of the inferomedial meniscal fragment displacement and a more correct planning of arthroscopy with a strong reduction of repeat interventions [it

Structural knee joint pathology in patients aged 40 years or older with meniscal tears

DEFF Research Database (Denmark)

Pihl, Kenneth; Englund, Martin; Lohmander, L S

2017-01-01

Purpose: Recent studies have challenged the tenet that mechanical symptoms of the knee (i.e. the sensation of catching or locking) are caused by degenerative meniscal tears per se and relieved by surgery. We explored the potential associations between meniscal and other knee joint pathologies...... identified at meniscal surgery with the presence of patient-reported mechanical symptoms. Methods: This study included patients aged 40 years or older undergoing surgery for a meniscal tear from the Knee Arthroscopy Cohort Southern Denmark (KACS). Patients were consecutively recruited from February 2013...... score (KOOS), together with information on previous meniscal surgery. At arthroscopy, the operating surgeon recorded information about specific meniscal pathology (tear location, depth, type, length, meniscal tissue quality and circumferential and radial location) and other structural knee pathologies...

Meniscal pathology in children: differences and similarities with the adult meniscus

Energy Technology Data Exchange (ETDEWEB)

Francavilla, Michael L.; Restrepo, Ricardo; Zamora, Kathryn W.; Sarode, Vijaya [Department of Radiology, Miami Children' s Hospital, Miami, FL (United States); Swirsky, Stephen M. [Department of Orthopedics, Miami Children' s Hospital, Miami, FL (United States); Mintz, Douglas [Hospital for Special Surgery, New York, NY (United States)

2014-08-15

The normal meniscus undergoes typical developmental changes during childhood, reaching a mature adult appearance by approximately 10 years of age. In addition to recognizing normal meniscal appearances in children, identifying abnormalities - such as tears and the different types of discoid meniscus and meniscal cysts, as well as the surgical implications of these abnormalities - is vital in pediatric imaging. The reported incidence of meniscal tears in adolescents and young adults has increased because of increased sports participation and more widespread use of MRI. This review discusses the normal appearance of the pediatric meniscus, meniscal abnormalities, associated injuries, and prognostic indicators for repair. (orig.)

Meniscal pathology in children: differences and similarities with the adult meniscus

International Nuclear Information System (INIS)

Francavilla, Michael L.; Restrepo, Ricardo; Zamora, Kathryn W.; Sarode, Vijaya; Swirsky, Stephen M.; Mintz, Douglas

2014-01-01

The normal meniscus undergoes typical developmental changes during childhood, reaching a mature adult appearance by approximately 10 years of age. In addition to recognizing normal meniscal appearances in children, identifying abnormalities - such as tears and the different types of discoid meniscus and meniscal cysts, as well as the surgical implications of these abnormalities - is vital in pediatric imaging. The reported incidence of meniscal tears in adolescents and young adults has increased because of increased sports participation and more widespread use of MRI. This review discusses the normal appearance of the pediatric meniscus, meniscal abnormalities, associated injuries, and prognostic indicators for repair. (orig.)

Meniscal injuries in the young, athletically active patient.

Science.gov (United States)

Poulsen, Matthew R; Johnson, Darren L

2011-02-01

Meniscal injuries are common in young physically active individuals, particularly those who are involved in contact level 1 sports that involve frequent pivoting, such as soccer and American football. This is a unique population because of their high physical activity at a young age, and it is important that correct diagnosis and appropriate treatment are provided, as the medial and lateral menisci are essential for normal knee function. In this article, we review the anatomy and function of the meniscus, the epidemiology of meniscal tears, and mechanism(s) of injury. Important concomitant injuries are also discussed. When making a diagnosis, relevant patient history, physical examination, and appropriate imaging studies are required. Nonoperative treatment is rarely successful for treating meniscal tears in young athletes, and therefore repair of the torn menisci is often required. We also discuss partial resection (which should only be performed when repair is not possible), as well as rehabilitation protocols after repair has been performed. All of these factors associated with meniscal injuries are important for a physician when diagnosing and treating these often complex injuries.

Similar failure rate in immediate post-operative weight bearing versus protected weight bearing following meniscal repair on peripheral, vertical meniscal tears.

Science.gov (United States)

Perkins, Bryan; Gronbeck, Kyle R; Yue, Ruixian Alexander; Tompkins, Marc A

2017-08-16

Post-operative weight bearing after meniscal repair is a point of debate among physicians. This study sought to evaluate whether patients adhering to an immediate WBAT rehabilitation programme have a higher failure rate compared to those adhering to a more traditional, protected, NWB status following meniscal repair. The null hypothesis was that there would be no difference in failure between the two groups. A retrospective review of meniscal repair patients greater than 5 years from surgery was performed for patients receiving meniscal repair treatment. Patients were categorized by post-surgical weight-bearing status, either NWB or WBAT, and then analysed for failure of repair. Failure was defined as re-operation on the torn meniscus. The study controlled for variables including age at surgery, sex, height, weight, and BMI, classification of tear type, acuity of the tear, repair location (medial or lateral), repair location within the meniscus, repair technique, and concomitant procedures. Re-operations were performed in 61 of 157 patients [38.9%]. There was no difference between weight-bearing groups for failure of meniscus repair (n.s.). The tears were acute vertical tears located in the posterior horn and body. For the 61 patients with re-operation, the average time to re-operation was 2.2 years with 10 [16%] > 5 years from surgery, 17 [28%] 2-5 years from surgery, and 34 [56%] bearing groups for rate of re-operation (n.s.). Weight bearing as tolerated after meniscal repair for peripheral, vertical tears does not result in a higher failure rate than traditional, non-weight bearing over a five-year follow-up period. The clinical relevance is that, based on these data, it may be appropriate to allow weight bearing as tolerated following meniscal repair of peripheral, vertical tears. Retrospective cohort study, Level III.

Meniscal allograft transplantation: a meta-analysis

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De Bruycker Manolito

2017-01-01

Full Text Available Purpose: This meta-analysis evaluates the mid- to long-term survival outcome of MAT (meniscal allograft transplantation. Potential prognosticators, with particular focus on chondral status and age of the patient at the time of transplantation, were also analysed. Study design: Meta-analysis. Methods: An online database search was performed using following search string: “meniscal allograft transplantation” and “outcome”. A total of 65 articles were analysed for a total of 3157 performed MAT with a mean follow-up of 5.4 years. Subjective and clinical data was analysed. Results: The subjective and objective results of 2977 patients (3157 allografts were analysed; 70% were male, 30% were female. Thirty-eight percent received an isolated MAT. All other patients underwent at least one concomitant procedure. Lysholm, Knee injury and Osteoarthritis Outcome (KOOS, International Knee Documentation Committee (IKDC and Visual Analogue Scale (VAS scores were analysed. All scores showed a good patient satisfaction at long-term follow-up. The mean overall survival rate was 80.9%. Complication rates were comparable to standard meniscal repair surgery. There was a degenerative evolution in osteoarthritis with at least one grade in 1760 radiographically analysed patients. Concomitant procedures seem to have no effect on the outcome. Age at transplantation is a negative prognosticator. The body mass index (BMI of the patient shows a slightly negative correlation with the outcome of MAT. Conclusions: MAT is a viable solution for the younger patient with chronic pain in the meniscectomised knee joint. The complications are not severe and comparable to meniscal repair. The overall failure rate at final follow-up is acceptable and the allograft heals well in most cases, but MAT cannot be seen as a definitive solution for post-meniscectomy pain. The correct approach to the chronic painful total meniscectomised knee joint thus requires consideration of all

Scaffold architecture and fibrin gels promote meniscal cell proliferation

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Pawelec, K. M., E-mail: pawelec.km@gmail.com, E-mail: jw626@cam.ac.uk; Best, S. M.; Cameron, R. E. [Cambridge Centre for Medical Materials, Materials Science and Metallurgy Department, University of Cambridge, Cambridge CB3 0FS (United Kingdom); Wardale, R. J., E-mail: pawelec.km@gmail.com, E-mail: jw626@cam.ac.uk [Division of Trauma and Orthopaedic Surgery, Department of Surgery, University of Cambridge, Cambridge CB2 2QQ (United Kingdom)

2015-01-01

Stability of the knee relies on the meniscus, a complex connective tissue with poor healing ability. Current meniscal tissue engineering is inadequate, as the signals for increasing meniscal cell proliferation have not been established. In this study, collagen scaffold structure, isotropic or aligned, and fibrin gel addition were tested. Metabolic activity was promoted by fibrin addition. Cellular proliferation, however, was significantly increased by both aligned architectures and fibrin addition. None of the constructs impaired collagen type I production or triggered adverse inflammatory responses. It was demonstrated that both fibrin gel addition and optimized scaffold architecture effectively promote meniscal cell proliferation.

Effective Treatment of an Apparent Meniscal Injury Using the Mulligan Concept

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Alex J. Rhinehart

2015-05-01

Full Text Available Objective: Present a clinic case demonstrating the effectiveness of the Mulligan Concept (MC in treating an apparent meniscal injury. The utilization of the MC in the evaluation and treatment of a 20-year-old soccer player with an apparent acute meniscal injury is presented. Background: Meniscal injuries are common knee injuries. The MC is a therapeutic intervention strategy applied as both a treatment-based evaluation and therapeutic intervention. Treatment: The patient was successfully treated in four treatment sessions using the MC. The patient experienced minimal clinically-important differences on a variety of global and regional patient-rated outcomes. Uniqueness: To the author’s knowledge, there are currently no published case reports of using the MC in clinical practice to treat an apparent meniscal pathology. Conclusion: The MC can be utilized as an evaluation and treatment technique in patients suspected of having meniscal pathology in the knee.

MRI follow-up of conservatively treated meniscal knee lesions in general practice

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Oei, Edwin H.G.; Hunink, M.G.M. [University Medical Center Rotterdam, Program for the Assessment of Radiological Technology (ART Program), Erasmus MC, Rotterdam (Netherlands); University Medical Center Rotterdam, Department of Radiology, Erasmus MC, Rotterdam (Netherlands); University Medical Center Rotterdam, Department of Epidemiology, Erasmus MC, Rotterdam (Netherlands); Koster, Ingrid M. [University Medical Center Rotterdam, Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Maasstad Ziekenhuis, Department of Radiology, Rotterdam (Netherlands); Hensen, Jan-Hein J.; Vroegindeweij, Dammis [Maasstad Ziekenhuis, Department of Radiology, Rotterdam (Netherlands); Boks, Simone S. [University Medical Center Rotterdam, Department of General Practice, Erasmus MC, Rotterdam (Netherlands); Maasstad Ziekenhuis, Department of Radiology, Rotterdam (Netherlands); Diaconessenhuis Meppel, Department of Radiology, Meppel (Netherlands); Wagemakers, Harry P.A.; Koes, Bart W.; Bierma-Zeinstra, Sita M.A. [University Medical Center Rotterdam, Department of General Practice, Erasmus MC, Rotterdam (Netherlands)

2010-05-15

To evaluate meniscal status change on follow-up MRI after 1 year, prognostic factors and association with clinical outcome in patients with conservatively treated knee injury. We analysed 403 meniscal horns in 101 conservatively treated patients (59 male; mean age 40 years) in general practice who underwent initial knee MRI within 5 weeks of trauma. We performed ordinal logistic regression analysis to analyse prognostic factors for meniscal change on follow-up MRI after 1 year, and we assessed the association with clinical outcome. On follow-up MRI 49 meniscal horns had deteriorated and 18 had improved. Age (odds ratio [OR] 1.3/decade), body weight (OR 1.2/10 kg), total anterior cruciate ligament (ACL) rupture on initial MRI (OR 2.4), location in the posterior horn of the medial meniscus (OR 3.0) and an initial meniscal lesion (OR 0.3) were statistically significant predictors of meniscal MRI appearance change after 1 year, which was not associated with clinical outcome. In conservatively treated patients, meniscal deterioration on follow-up MRI 1 year after trauma is predicted by higher age and body weight, initial total ACL rupture, and location in the medial posterior horn. Change in MRI appearance is not associated with clinical outcome. (orig.)

Meniscal configuration using magnetic resonance imaging; Configuracao meniscal pela ressonancia magnetica

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Fernandes, Arthur da Rocha C.; Turrini, Elisabete; Karoauk, Teresa C.C.; Lederman, Henrique M. [Escola Paulista de Medicina, Sao Paulo, SP (Brazil). Dept. de Diagnostico por Imagem

1997-04-01

The authors present a review of the normal meniscal configuration and correlation with anatomic specimens. The images were obtained by magnetic resonance imaging. The images were obtained by magnetic resonance imaging. The authors emphasize the importance of knowing the relationship between the meniscus and the adjacent anatomic structures. (author) 31 refs., 10 figs., tabs.

Snapping Knee Caused by Medial Meniscal Cyst

Directory of Open Access Journals (Sweden)

Tsuyoshi Ohishi

2014-01-01

Full Text Available Snapping phenomenon around the medial aspect of the knee is rare. We present this case of snapping knee caused by the sartorius muscle over a large medial meniscal cyst in a 66-year-old female. Magnetic resonance images demonstrated a large medial meniscal cyst with a horizontal tear of the medial meniscus. Arthroscopic cyst decompression with limited meniscectomy resulted in the disappearance of snapping, and no recurrence of the cyst was observed during a 2-year follow-up period.

Meniscal abnormalities in soccer players: prevalence and MR imaging

International Nuclear Information System (INIS)

Song, In Sup; Lee, Jong Ik; Kwak, Byeung Kook; Shim, Hyung Jin; Lee, Jong Beum; Lee, Yong Chul; Kim, Kun Sang; Seo, Kyung Mook

1995-01-01

We aimed to know the prevalence of abnormal meniscal signal on MR imaging in asymptomatic soccer players and its radiologic significance. Using T1 and gradient echo T2 weighted sagittal and coronal MR image, 48 knees in twenty-four full time soccer players were evaluated for the meniscal abnormalities, the status of ligament and existence of joint effusion. Meniscal abnormalities were interpreted using grading system of Lotysch. By using Chi-square method. We analyzed the existence of joint effusion could divide the healing state and healed state of the meniscus. The prevalence of Grade 2 and more and Grade 3 were 42% and 39% of asymptomatic knees. In the 24 knees with meniscus tear, nine of the 14 asymptomatic knee showed effusion while eight of the 10 symptomatic knee did. Of 24 knees with meniscal tear, only eleven knees were related to previous history of major knee trauma. The prevalence of meniscal abnormalities on MR imaging in asymptomatic soccer players was higher (grade 3: 39%) than we expected. The joint effusion was not helpful to divide the healing state and healed state of the meniscus. So we suggest baseline MR imaging in the athletes who have been using the knee vigorously could give decisive information for the interpretation of subsequent MRI that may be performed when the players wounded

Integrity of articular cartilage on T2 mapping associated with meniscal signal change

International Nuclear Information System (INIS)

Kai, Brian; Mann, Sumeer A.; King, Chris; Forster, Bruce B.

2011-01-01

Objective: The purpose of this study was to investigate the relationship between T2 relaxation values (T2 RVs) within the superficial zone of articular cartilage and different types of meniscal degeneration/tear. Materials and methods: A review of 310 consecutive knee MRIs which included an 8 echo T2 relaxation sequence, in patients referred for standard clinical indications, was performed independently and in blinded fashion by 2 observers. The posterior horns of the medial and lateral menisci were each evaluated and divided into 4 subgroups: Normal (control), Grade I/II meniscal signal, Grade III meniscal signal-simple tear (Grade III-S), and Grade III meniscal signal-complex tear (Grade III-C). After exclusion criteria were applied, the medial meniscal group consisted of 65 controls and 133 patients, while the lateral meniscal group consisted of 143 controls and 55 patients. T2 RVs were measured by an observer blinded to the clinical history and MRI grading. Measurements were obtained over the superficial zone of femoral and tibial articular cartilage adjacent to the center of the posterior horn of each meniscus to ensure consistency between measurements. Analysis of covariance adjusting for age and gender was used to compare T2 RVs between patients and controls. Results: T2 RVs were significantly increased in patients with Grade III-C meniscal tears compared to controls over the medial tibial plateau (MTP; p = 0.0001) and lateral tibial plateau (LTP; p = 0.0008). T2 RVs were not increased in patients with Grade III-C meniscal tears over the medial femoral condyle (MFC; p = 0.11) or lateral femoral condyle (LFC; p = 0.99). Grade I/II meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.15), LFC (p = 0.69), MTP (p = 0.42), or LTP (p = 0.50). Grade III-S meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.54), LFC (p = 0.43), MTP (p = 0.30), or LTP (p = 0.38). Conclusion: Grade III-C meniscal tears are associated with

Integrity of articular cartilage on T2 mapping associated with meniscal signal change

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Kai, Brian [Department of Radiology, University of British Columbia, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 (Canada); Mann, Sumeer A. [Department of Radiology, University of Alberta, Walter Mackenzie Health Sciences Center, Edmonton, AB, T6G 2B7 (Canada); King, Chris [Department of Radiology, University of British Columbia, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 (Canada); Forster, Bruce B., E-mail: bruce.forster@vch.ca [Department of Radiology, University of British Columbia, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 (Canada)

2011-09-15

Objective: The purpose of this study was to investigate the relationship between T2 relaxation values (T2 RVs) within the superficial zone of articular cartilage and different types of meniscal degeneration/tear. Materials and methods: A review of 310 consecutive knee MRIs which included an 8 echo T2 relaxation sequence, in patients referred for standard clinical indications, was performed independently and in blinded fashion by 2 observers. The posterior horns of the medial and lateral menisci were each evaluated and divided into 4 subgroups: Normal (control), Grade I/II meniscal signal, Grade III meniscal signal-simple tear (Grade III-S), and Grade III meniscal signal-complex tear (Grade III-C). After exclusion criteria were applied, the medial meniscal group consisted of 65 controls and 133 patients, while the lateral meniscal group consisted of 143 controls and 55 patients. T2 RVs were measured by an observer blinded to the clinical history and MRI grading. Measurements were obtained over the superficial zone of femoral and tibial articular cartilage adjacent to the center of the posterior horn of each meniscus to ensure consistency between measurements. Analysis of covariance adjusting for age and gender was used to compare T2 RVs between patients and controls. Results: T2 RVs were significantly increased in patients with Grade III-C meniscal tears compared to controls over the medial tibial plateau (MTP; p = 0.0001) and lateral tibial plateau (LTP; p = 0.0008). T2 RVs were not increased in patients with Grade III-C meniscal tears over the medial femoral condyle (MFC; p = 0.11) or lateral femoral condyle (LFC; p = 0.99). Grade I/II meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.15), LFC (p = 0.69), MTP (p = 0.42), or LTP (p = 0.50). Grade III-S meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.54), LFC (p = 0.43), MTP (p = 0.30), or LTP (p = 0.38). Conclusion: Grade III-C meniscal tears are associated with

A comparison of arthrography to clinical diagnostics for diagnosing meniscal lesions

International Nuclear Information System (INIS)

Neuer, H.

1982-01-01

A comparative investigation as to the exactness of clinical and arthrographical diagnostics was carried out on 176 patients who were clinically examined and operated on in the period of 1972-1980. Using solely clinical diagnostics, the total rate of exactness was 90,9%, the exactness regarding the internal meniscal lesion being significantly higher (94.2%) than that regarding external meniscal lesion (76.7%). Using solely arthrographic diagnostics, the total rate of exactness was 82%, the rate for internal meniscus being significantly lower (83.9%) than that obtained using clinical diagnostics. As for the external meniscus, the exactness of arthrography differs only slightly from clinical diagnostics with 74.7%. The most frequent sources of error in arthorgraphy were found to be lesions of the posterior horn at the internal meniscus. In cases of external meniscal lesions, especially when an internal meniscal lesion was existing at the same time, both examination methods failed in 5 cases. For routine diagnosing of meniscal lesions, arthrography is not necessary. An accurate clinical examination and anamnesis bring very good and exact results and should therefore be given absolute priority. (orig./MG) [de

The role of an axial MR scan on the diagnosis a meniscal tear of the knee joint

International Nuclear Information System (INIS)

Yeom, Suk Keu; Kim, Baek Hyun; Hong, Suk Joo; Seol, Hae Young

2007-01-01

To evaluate the role of standard axial MR images for the diagnosis for meniscal tears of the knee. Forty-five patients with a prior MRI examination that underwent arthroscopic surgery of the knee due to clinical impression of a meniscal tear were included in the study group. The sequence for meniscal evaluation was an axial fat-saturated proton density-weighted image with a 4 mm slice thickness. Axial MR images were independently reviewed by two radiologists and were compared with findings of arthroscopy. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the axial MR scan for the diagnosis of the meniscal tear were calculated. A total 90 menisci of 45 patients were evaluated in the axial MR scans. Forty-two patients had meniscal tears, and two of the patients had tears in both menisci; thus, a total of 44 meniscal tears were found by arthroscopy. For meniscal tears, the sensitivity of the axial plane was 76.2%, the specificity was 89.1% and the accuracy was 81.1%. False negative meniscal tears were seen in 12 cases and false positive meniscal tears were seen in 5 cases on the axial MR images. In standard knee MRI examinations, axial images may be valuable for the detection and localization of meniscal tears

Ultrasound-guided percutaneous drainage of meniscal cysts: preliminary clinical experience

International Nuclear Information System (INIS)

MacMahon, P.J.; Brennan, D.D.; Duke, D.; Forde, S.; Eustace, S.J.

2007-01-01

Aim: To evaluate the efficacy of ultrasound-guided percutaneous drainage of symptomatic meniscal cysts. Materials and methods: Patients with lateral knee joint tenderness and swelling and confirmed meniscal cyst on magnetic resonance imaging (MRI) were consecutively enrolled for ultrasound-guided percutaneous cyst aspiration. Cysts were injected with local anaesthetic and steroid before completion of procedure. All 18 patients (all male, average age 33 years) were subsequently followed up (average time 10 months) and meniscal cyst symptoms assessed by questionnaire. Fischer's exact test used to analyse the data. Results: In every case the procedure was well tolerated, and each patient indicated that they would be willing to have a repeat procedure in the future. Ten patients reported complete resolution of symptoms secondary to therapeutic cyst aspiration and had resumed participation in high-performance sport. Two patients reported a satisfactory sustained response, reporting only occasional 'twinges of pain'. In the remaining six patients, symptoms returned after an initial pain-free period. The pain-free period ranged from 1-8 weeks. In this study, patient outcome did not significantly correlate with any meniscal cyst characteristic. Conclusion: Ultrasound-guided percutaneous aspiration of meniscal cysts is a well-tolerated, simple, and safe procedure. In this small patient series, it was associated with positive early results with favourable outcomes in the mid to long-term. It should be considered in patients unsuitable for surgical debridement or as an interim therapy if surgery is delayed or postponed

MRI versus ultrasonography to assess meniscal abnormalities in acute knees.

Science.gov (United States)

Cook, James L; Cook, Cristi R; Stannard, James P; Vaughn, Gavin; Wilson, Nichole; Roller, Brandon L; Stoker, Aaron M; Jayabalan, Prakash; Hdeib, Moses; Kuroki, Keiichi

2014-08-01

While magnetic resonance imaging (MRI) is often considered the "gold standard" diagnostic imaging modality for detection of meniscal abnormalities, it is associated with misdiagnosis in as high as 47% of cases, is costly, and is not readily available to a large number of patients. Ultrasonographic examination of the knee has been reported to be an effective diagnostic tool for this purpose with the potential to overcome many of the shortcomings of MRI. The purpose of this study is to determine the clinical usefulness of ultrasonography for diagnosis of meniscal pathology in patients with acute knee pain and compare its diagnostic accuracy to MRI in a clinical setting. With Institutional Review Board approval, patients (n = 71) with acute knee pain were prospectively enrolled with informed consent. Preoperative MRI (1.5 T) was performed on each affected knee using the hospital's standard equipment and protocols and read by faculty radiologists trained in musculoskeletal MRI. Ultrasonographic assessments of each affected knee were performed by one of two faculty members trained in musculoskeletal ultrasonography using a 10 to 14 MHz linear transducer. Arthroscopic evaluation of affected knees was performed by one of three faculty orthopedic surgeons to assess and record all joint pathology, which served as the reference standard for determining presence, type, and severity of meniscal pathology. All evaluators for each diagnostic modality were blinded to all other data. Data were collected and compared by a separate investigator to determine sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), correct classification rate (CCR), likelihood ratios (LR[+] and LR[-]), and odds ratios. Preoperative ultrasonographic assessment of meniscal pathology was associated with Sn = 91.2%, Sp = 84.2%, PPV = 94.5%, NPV = 76.2%, CCR = 89.5%, LR(+) = 5.78, and LR(-) = 0.10. Preoperative MRI assessment of

Cost effectiveness of meniscal allograft for torn discoid lateral meniscus in young women.

Science.gov (United States)

Ramme, Austin J; Strauss, Eric J; Jazrawi, Laith; Gold, Heather T

2016-09-01

A discoid meniscus is more prone to tears than a normal meniscus. Patients with a torn discoid lateral meniscus are at increased risk for early onset osteoarthritis requiring total knee arthroplasty (TKA). Optimal management for this condition is controversial given the up-front cost difference between the two treatment options: the more expensive meniscal allograft transplantation compared with standard partial meniscectomy. We hypothesize that meniscal allograft transplantation following excision of a torn discoid lateral meniscus is more cost-effective compared with partial meniscectomy alone because allografts will extend the time to TKA. A decision analytic Markov model was created to compare the cost effectiveness of two treatments for symptomatic, torn discoid lateral meniscus: meniscal allograft and partial meniscectomy. Probability estimates and event rates were derived from the scientific literature, and costs and benefits were discounted by 3%. One-way sensitivity analyses were performed to test model robustness. Over 25 years, the partial meniscectomy strategy cost $10,430, whereas meniscal allograft cost on average $4040 more, at $14,470. Partial meniscectomy postponed TKA an average of 12.5 years, compared with 17.30 years for meniscal allograft, an increase of 4.8 years. Allograft cost $842 per-year-gained in time to TKA. Meniscal allografts have been shown to reduce pain and improve function in patients with discoid lateral meniscus tears. Though more costly, meniscal allografts may be more effective than partial meniscectomy in delaying TKA in this model. Additional future long term clinical studies will provide more insight into optimal surgical options.

Is radiographic measurement of bony landmarks reliable for lateral meniscal sizing?

Science.gov (United States)

Yoon, Jung-Ro; Kim, Taik-Seon; Lim, Hong-Chul; Lim, Hyung-Tae; Yang, Jae-Hyuk

2011-03-01

The accuracy of meniscal measurement methods is still in debate. The authors' protocol for radiologic measurements will provide reproducible bony landmarks, and this measurement method of the lateral tibial plateau will correlate with the actual anatomic value. Controlled laboratory study. Twenty-five samples of fresh lateral meniscus with attached proximal tibia were obtained during total knee arthroplasty. Each sample was obtained without damage to the meniscus and bony attachment sites. The inclusion criterion was mild to moderate osteoarthritis in patients with mechanical axis deviation of less than 15°. Knees with lateral compartment osteoarthritic change or injured or degenerated menisci were excluded. For the lateral tibial plateau length measurements, the radiographic beam was angled 10° caudally at neutral rotation, which allowed differentiation of the lateral plateau cortical margins from the medial plateau. The transition points were identified and used for length measurement. The values of length were then compared with the conventional Pollard method and the anatomic values. The width measurement was done according to Pollard's protocol. For each knee, the percentage deviation from the anatomic dimension was recorded. Intraobserver error and interobserver error were calculated. The deviation of the authors' radiographic length measurements from anatomic dimensions was 1.4 ± 1.1 mm. The deviation of Pollard's radiographic length measurements was 4.1 ± 2.0 mm. With respect to accuracy-which represents the frequency of measurements that fall within 10% of measurements-the accuracy of authors' length was 98%, whereas for Pollard's method it was 40%. There was a good correlation between anatomic meniscal dimensions and each radiologic plateau dimensions for lateral meniscal width (R(2) = .790) and the authors' lateral meniscal length (R(2) = .823) and fair correlation for Pollard's lateral meniscal length (R(2) = .660). The reliability of each

Sonographic Imaging of Meniscal Subluxation in Patients with Radiographic Knee Osteoarthritis

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Chun-Hung Ko

2007-09-01

Conclusion: Meniscal subluxation is a prominent feature on weight-bearing sonographic imaging in patients with radiographic osteoarthritis and could be considered as a risk factor for the development of knee osteoarthritis. By using musculoskeletal ultrasonography, one can detect this occult meniscal derangement early before the appearance of radiographic signs of osteoarthritis.

Patient reported outcomes in patients undergoing arthroscopic partial meniscectomy for traumatic or degenerative meniscal tears

DEFF Research Database (Denmark)

Thorlund, Jonas Bloch; Englund, Martin; Christensen, Robin

2017-01-01

OBJECTIVES: To compare patient reported outcomes from before surgery to 52 weeks after surgery between individuals undergoing arthroscopic partial meniscectomy for traumatic meniscal tears and those for degenerative meniscal tears. DESIGN: Comparative prospective cohort study. SETTING: Four public......-55, and undergoing arthroscopic partial meniscectomy for a traumatic or degenerative meniscal tear (defined by a combination of age and symptom onset). INTERVENTIONS: Both participant groups underwent arthroscopic partial meniscectomy for a meniscal tear, with operating surgeons recording relevant information......% women) with a traumatic or degenerative meniscal tear (n=141, mean age 38.7 years (standard deviation 10.9); n=256, 46.6 years (6.4); respectively) were included in the main analysis. At 52 weeks after arthroscopic partial meniscectomy, 55 (14%) patients were lost to follow-up. Statistically...

MR imaging of displaced meniscal tears of the knee. Importance of a 'disproportional posterior horn sign'

International Nuclear Information System (INIS)

Chen, H.C.; Hsu, C.Y.; Shih, T.T.F.; Huang, K.M.; Li, Y.W.

2001-01-01

Purpose: Meniscal tears associated with displaced fragments are clinically significant. We propose the 'disproportional posterior horn sign' as a supportive criterion to identify a posterocentrally displaced meniscal fragment on MR imaging studies. If the meniscal posterior horn in the central portion appears larger than that in the peripheral section, it is considered positive for 'disproportional posterior horn sign'. Material and Methods: MR images obtained in 42 patients with 43 lesions, confirmed to have displaced meniscal tears, were included in this study. The MR images were retrospectively evaluated for the presence of the 'disproportional posterior horn sign', as well as the other known signs. Results: The 'disproportional posterior horn sign' was seen in 9 (20.9%) of 43 lesions, including 1 lateral discoid meniscal tear, 5 lateral meniscal tears and 3 medial meniscal tears. Five of them also had other signs of a displaced meniscal fragment. However, the remaining 4 cases only exhibited the 'disproportional posterior horn sign'. For the other MR signs, the 'absent bow tie sign' was detected in 40 (93%) of 43 lesions, the 'flipped meniscus sign' in 27 (62.8%) of 43 lesions, the 'double posterior cruciate ligament sign' in 17 (39.5%) of 43 lesions and the 'notch fragment sign' in 22 (51.2%) of 43 lesions. Conclusion: The 'disproportional posterior horn sign' is helpful in demonstrating a posterocentrally displaced meniscal fragment, especially when other characteristic signs are unremarkable or absent

The role of biomaterials in the treatment of meniscal tears

Directory of Open Access Journals (Sweden)

Crystal O. Kean

2017-11-01

Full Text Available Extensive investigations over the recent decades have established the anatomical, biomechanical and functional importance of the meniscus in the knee joint. As a functioning part of the joint, it serves to prevent the deterioration of articular cartilage and subsequent osteoarthritis. To this end, meniscus repair and regeneration is of particular interest from the biomaterial, bioengineering and orthopaedic research community. Even though meniscal research is previously of a considerable volume, the research community with evolving material science, biology and medical advances are all pushing toward emerging novel solutions and approaches to the successful treatment of meniscal difficulties. This review presents a tactical evaluation of the latest biomaterials, experiments to simulate meniscal tears and the state-of-the-art materials and strategies currently used to treat tears.

MRI follow-up of conservatively treated meniscal knee lesions in general practice

NARCIS (Netherlands)

E.H.G. Oei (Edwin); I.M. Koster (Ingrid); J.H.J. Hensen; S.S. Boks (Simone); H.P.A. Wagemakers (Harry); B.W. Koes (Bart); D. Vroegindeweij (Dammis); S.M. Bierma-Zeinstra (Sita); M.G.M. Hunink (Myriam)

2010-01-01

textabstractObjective: To evaluate meniscal status change on follow-up MRI after 1 year, prognostic factors and association with clinical outcome in patients with conservatively treated knee injury. Methods: We analysed 403 meniscal horns in 101 conservatively treated patients (59 male; mean age 40

Cell Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath

Science.gov (United States)

2017-07-01

to subsequently guide tissue regeneration , for example, by seeded tissue progenitor cells . To achieve this objective, the first step is to develop...AWARD NUMBER: W81XWH-15-1-0104 TITLE: Cell -Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER Cell -Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath 5b. GRANT NUMBER W81XWH-15-1-0104 5c. PROGRAM

Accuracy of 3-Tesla MR and MR arthrography in diagnosis of meniscal retear in the post-operative knee

Energy Technology Data Exchange (ETDEWEB)

Magee, Thomas [NSI, Merritt Island, FL (United States); University of Central Florida School of Medicine, Orlando, FL (United States)

2014-08-15

This study assesses the accuracy of 3-Tesla (3-T) conventional MR imaging, 3-T MR arthrography, and the combined use of conventional MR and MR arthrography in the diagnosis of meniscal retears as compared with arthroscopy. The study also assess whether there are false-negative cases in which injected contrast does not extend into the meniscus despite a meniscal retear being seen on arthroscopy. One hundred consecutive knee MR arthrograms performed on patients with previous knee surgery were reviewed retrospectively. 3-T conventional MR imaging, 3-T MR arthrography, and the combined use of conventional MR and MR arthrography were assessed for meniscal retears as compared with arthroscopy. The criterion used to diagnose a meniscal retear on MR arthrogram was injected contrast tracking into the meniscus. All patients underwent second-look arthroscopy. Seventy-four patients had conventional MR findings consistent with a meniscal retear. In 83 of the 100 patients, intraarticular contrast helped in demonstrating a retear. In ten patients, there were MR findings consistent with a meniscal retear despite intra-articular contrast not tracking into the meniscus. Ninety-four of the 100 patients had meniscal retears on second-look arthroscopy. Three-Tesla conventional MR examination was 78 % sensitive and 75 % specific, MR arthrogram examination was 88 % sensitive and 100 % specific, and the combined use of MR and MR arthrogram imaging was 98 % sensitive and 75 % specific in the diagnosis of a meniscal retear. The combined use of 3-T MR and MR arthrography allows for high sensitivity and specificity in meniscal retear detection. In some patients, intraarticular contrast will not track into a meniscal retear. When MR findings are consistent with a meniscal retear but contrast does not extend into the meniscus, a meniscal retear is likely. (orig.)

MR diagnosis of meniscal tears of the knee: analysis of error patterns.

Science.gov (United States)

Van Dyck, Pieter; Gielen, Jan; D'Anvers, Jan; Vanhoenacker, Filip; Dossche, Lieven; Van Gestel, Jozef; Parizel, Paul M

2007-11-01

Despite high accuracy of magnetic resonance imaging (MRI) for diagnosing meniscal tears, MR findings do not always agree with surgical findings. We performed a blinded, retrospective study to analyze the nature and frequency of errors in the MR diagnosis of meniscal tears. Medical records of 100 consecutive patients who underwent MR and arthroscopy of the knee at our institution were reviewed. Twelve patients underwent prior meniscal surgery. Twenty-three patients had 27 discrepancies between MR and surgical findings. These were independently reviewed by two additional musculoskeletal radiologists in a double blinded fashion. Original incorrect diagnoses were categorized as either unavoidable, interpretation error or equivocal for meniscal tear. MR accuracy was 88% for the medial and 85% for the lateral meniscus. Of 27 incorrect MR diagnoses, 12 (44%) were unavoidable, 10 (37%) equivocal and 5 (19%) interpretation errors. Of the 67 medial meniscal tears, 12 (18%) were missed. Eight (67%) of these 12 were categorized as equivocal, including three postoperative menisci. Of 30 lateral tears, 12 (40%) were missed, 7 (58%) of which were categorized as unavoidable. Of these 12, 11 (92%) showed fraying of the inner edge, which was shaved at arthroscopy (n = 8) or had stable tear treated conservatively (n = 3). There were three false-positive diagnoses, all occuring in the lateral meniscus, two of which were unavoidable and one interpretation error. Of all missed lateral meniscal tears, most are unavoidable and related to confusion between what represents fraying and what represents a tear. Unavoidable false-positive diagnoses are infrequent and may be related to incomplete arthroscopic evaluation. Subtle or equivocal findings still make MR diagnosis difficult, even for experienced radiologists.

Impact of type of meniscal tear on radiographic and symptomatic knee osteoarthritis

DEFF Research Database (Denmark)

Englund, M; Roos, Ewa M.; Lohmander, L S

2003-01-01

To investigate long-term radiographic and patient-relevant outcome of isolated limited meniscectomy with regard to type of meniscal tear and extent of surgical resection.......To investigate long-term radiographic and patient-relevant outcome of isolated limited meniscectomy with regard to type of meniscal tear and extent of surgical resection....

Gene expression and gene therapy imaging

International Nuclear Information System (INIS)

Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

2007-01-01

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

Epidemiology of isolated meniscal injury and its effect on performance in athletes from the National Basketball Association.

Science.gov (United States)

Yeh, Peter C; Starkey, Chad; Lombardo, Stephen; Vitti, Gary; Kharrazi, F Daniel

2012-03-01

The current incidence and outcomes of meniscal injury have not been quantified in professional athletes. To describe the incidence, risk, amount of time lost, and effect on performance for isolated meniscal injury in athletes from the National Basketball Association (NBA). Demographic factors predicting the risk of meniscal tears and the effect of injury in return to play were also investigated. Descriptive epidemiology study. A centralized database was queried to identify meniscal injuries occurring in the NBA over 21 seasons. The frequency of injury, time lost, game exposures, and incidence, rate, and risk were calculated. The preinjury and postinjury player efficiency rating (PER) was used to identify changes in player performance. We identified 129 isolated meniscal tears in NBA athletes during a 21-season span. From this number, 77 (59.7%) involved the lateral meniscus and 52 (40.3%) the medial meniscus. Injuries occurred more frequently in games. The lateral meniscus had a statistically significant higher injury rate. Both left and right knees were equally affected. The number of days missed for lateral meniscal tears and medial meniscal tears was 43.8 ± 35.7 days and 40.9 ± 29.7 days, respectively, and was not statistically different. There was a significant inverse relationship between age and rate of lateral meniscal tears, with lateral meniscal tears more likely to occur up to age 30 years; beyond that medial meniscal tears were more common. Players with a body mass index (BMI) greater than 25 had a significantly increased risk of meniscal tears compared with players with a BMI less than 25, specifically with an increased risk of lateral meniscal tears. Twenty-five players (19.4%) did not return to play. For those who did, upon returning to competition, there was no statistical change in PER from their preinjury status, and the mean number of seasons completed was 4.1 ± 3.7 seasons. The lateral meniscus is more frequently torn than the medial meniscus

A new hydrogel for the conservative treatment of meniscal lesions: a randomized controlled study.

Science.gov (United States)

Zorzi, Claudio; Rigotti, Stefano; Screpis, Daniele; Giordan, Nicola; Piovan, Gianluca

2015-01-01

this study aimed to investigate the efficacy of intra-articular (IA) administration of a hydrogel formulation obtained from a hyaluronic acid (HA) derivative (HYADD4(®)) in the management of meniscal tears and in meniscal tear repair. fifty subjects with degenerative meniscal tears were enrolled into this single-site, observer-blind, parallel-group study. Clinical evaluations were performed at baseline and after 14, 30 and 60 days. Clinical outcomes included: pain reduction (Visual Analog Scale), improvement of knee functionality (WOMAC questionnaire), reduction in length and depth of the meniscal lesion (MRI-confirmed) and SF-36 questionnaire scores. Local tolerability and safety were also investigated. a significant reduction in VAS pain (p< 0.001) in favor of HYADD4(®) was recorded at day 14 and maintained at all the follow-up assessments. Data on knee functionality were in line with the VAS pain assessment results. A significant reduction in length and depth of the meniscal lesion, assessed using MRI, was found in the HYADD4(®) group compared to the control group (p<0.001). the results of this study may indicate a new treatment option in the conservative management of patients complaining of pain due to meniscal tears. The MRI data suggest that the hydrogel formulation of HA used in this study may also play a role in the healing process of the lesion. Level I, prospective randomized clinical trial.

The relationship between prevalent medial meniscal intrasubstance signal changes and incident medial meniscal tears in women over a 1-year period assessed with 3.0 T MRI

Energy Technology Data Exchange (ETDEWEB)

Crema, Michel D. [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States); Ribeirao Preto School of Medicine, University of Sao Paulo (USP), Department of Biomechanics, Medicine and Rehabilitation of the Locomotor Apparatus, and Department of Internal Medicine, Radiology Division, Ribeirao Preto (Brazil); Institute of Diagnostic Imaging (IDI), Ribeirao Preto (Brazil); Hunter, David J. [The University of Sydney, Sydney School of Medicine, Sydney (Australia); Roemer, Frank W. [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States); Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Li, Ling [New England Baptist Hospital, Division of Research, Boston, MA (United States); Marra, Monica D. [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States); Institute of Diagnostic Imaging (IDI), Ribeirao Preto (Brazil); Nogueira-Barbosa, Marcello H. [Ribeirao Preto School of Medicine, University of Sao Paulo (USP), Department of Biomechanics, Medicine and Rehabilitation of the Locomotor Apparatus, and Department of Internal Medicine, Radiology Division, Ribeirao Preto (Brazil); Hellio Le Graverand, Marie-Pierre; Wyman, Bradley T. [Pfizer Global Research and Development, New London, CT (United States); Guermazi, Ali [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States)

2011-08-15

Intrasubstance meniscal signal changes not reaching the articular surface on fast spin echo (FSE) sequences are considered to represent mucoid degeneration on MRI. The aim of this study was to evaluate the association of prevalent intrasubstance signal changes with incident tears of the medial meniscus detected on 3.0 T MRI over a 1-year period. A total of 161 women aged {>=}40 years participated in a longitudinal 1-year observational study of knee osteoarthritis. MRI (3.0 T) was performed at baseline and 12-month follow-up. The anterior horn, body, and posterior horn of the medial meniscus were scored by two experienced musculoskeletal radiologists using the Boston-Leeds Osteoarthritis Knee Score (BLOKS) system. Four grades were used to describe the meniscal morphology: grade 0 (normal), grade 1 (intrasubstance signal changes not reaching the articular surface), grade 2 (single tears), and grade 3 (complex tears and maceration). Fisher's exact test and the Cochran-Armitage trend test were performed to evaluate whether baseline intrasubstance signal changes (grade 1) predict incident meniscal tears/maceration (grades 2 and/or 3) in the same subregion of the medial meniscus, when compared to subregions without pathology as the reference group (grade 0). Medial meniscal intrasubstance signal changes at baseline did not predict tears at follow-up when evaluating the anterior and posterior horns (left-sided p-values 0.06 and 0.59, respectively). No incident tears were detected in the body. We could not demonstrate an association between prevalent medial meniscal intrasubstance signal changes with incident tears over a 1-year period. (orig.)

The relationship between prevalent medial meniscal intrasubstance signal changes and incident medial meniscal tears in women over a 1-year period assessed with 3.0 T MRI

International Nuclear Information System (INIS)

Crema, Michel D.; Hunter, David J.; Roemer, Frank W.; Li, Ling; Marra, Monica D.; Nogueira-Barbosa, Marcello H.; Hellio Le Graverand, Marie-Pierre; Wyman, Bradley T.; Guermazi, Ali

2011-01-01

Intrasubstance meniscal signal changes not reaching the articular surface on fast spin echo (FSE) sequences are considered to represent mucoid degeneration on MRI. The aim of this study was to evaluate the association of prevalent intrasubstance signal changes with incident tears of the medial meniscus detected on 3.0 T MRI over a 1-year period. A total of 161 women aged ≥40 years participated in a longitudinal 1-year observational study of knee osteoarthritis. MRI (3.0 T) was performed at baseline and 12-month follow-up. The anterior horn, body, and posterior horn of the medial meniscus were scored by two experienced musculoskeletal radiologists using the Boston-Leeds Osteoarthritis Knee Score (BLOKS) system. Four grades were used to describe the meniscal morphology: grade 0 (normal), grade 1 (intrasubstance signal changes not reaching the articular surface), grade 2 (single tears), and grade 3 (complex tears and maceration). Fisher's exact test and the Cochran-Armitage trend test were performed to evaluate whether baseline intrasubstance signal changes (grade 1) predict incident meniscal tears/maceration (grades 2 and/or 3) in the same subregion of the medial meniscus, when compared to subregions without pathology as the reference group (grade 0). Medial meniscal intrasubstance signal changes at baseline did not predict tears at follow-up when evaluating the anterior and posterior horns (left-sided p-values 0.06 and 0.59, respectively). No incident tears were detected in the body. We could not demonstrate an association between prevalent medial meniscal intrasubstance signal changes with incident tears over a 1-year period. (orig.)

Successful anterior cruciate ligament reconstruction and meniscal repair in osteogenesis imperfecta.

Science.gov (United States)

Park, Jae-Young; Cho, Tae-Joon; Lee, Myung Chul; Han, Hyuk-Soo

2018-03-20

A case of anterior cruciate ligament (ACL) reconstruction with meniscal repair in an osteogenesis imperfecta patient is reported. A 24-year-old female with osteogenesis imperfecta type 1a suffered from a valgus extension injury resulting in tear of ACL and medial meniscus. She underwent an arthroscopic-assisted ACL reconstruction and medial meniscus repair. Meniscal tear at the menisco-capsular junction of the posterior horn of medial meniscus was repaired with three absorbable sutures via inside-out technique. ACL reconstruction was then performed with a bone-patellar tendon-bone allograft. The patient was followed up for 1 year with intact ACL grafts and healed medial meniscus. This case report showed that successful ACL reconstruction and meniscal repair is possible in an osteogenesis imperfecta patient.Level of evidence V.

Cartilage Degeneration, Subchondral Mineral and Meniscal Mineral Densities in Hartley and Strain 13 Guinea Pigs

Science.gov (United States)

Sun, Yubo; Scannell, Brian P; Honeycutt, Patrick R; Mauerhan, David R; H, James Norton; Hanley Jr, Edward N

2015-01-01

Osteoarthritis is a joint disease involved in articular cartilage, subchondral bone, meniscus and synovial membrane. This study sought to examine cartilage degeneration, subchondral bone mineral density (BMD) and meniscal mineral density (MD) in male Hartley, female Hartley and female strain 13 guinea pigs to determine the association of cartilage degeneration with subchondral BMD and meniscal MD. Cartilage degeneration, subchondral BMD and meniscal MD in 12 months old guinea pigs were examined with histochemistry, X-ray densitometry and calcium analysis. We found that male Hartley guinea pigs had more severe cartilage degeneration, subchondral BMD and meniscal MD than female Hartley guinea pigs, but not female strain 13 guinea pigs. Female strain 13 guinea pigs had more severe cartilage degeneration and higher subchondral BMD, but not meniscal MD, than female Hartley guinea pigs. These findings indicate that higher subchondral BMD, not meniscal MD, is associated with more severe cartilage degeneration in the guinea pigs and suggest that abnormal subchondral BMD may be a therapeutic target for OA treatment. These findings also indicate that the pathogenesis of OA in the male guinea pigs and female guinea pigs are different. Female strain 13 guinea pig may be used to study female gender-specific pathogenesis of OA. PMID:26401159

Meniscal transplantation: procedures, outcomes, and rehabilitation

Directory of Open Access Journals (Sweden)

Young J

2017-05-01

Full Text Available James Young, Francois Tudor, Ahmed Mahmoud, Peter Myers Brisbane Orthopaedic & Sports Medicine Centre, Brisbane Private Hospital, Spring Hill, Brisbane, Queensland, Australia Abstract: Meniscal allograft transplantation (MAT is a possible treatment option for patients with joint pain after meniscectomy. It is necessary that the joint be aligned and stable. Current evidence shows that MAT improves pain and mechanical function in the mid to long term with patients reporting significantly improved outcomes at up to 15 years following surgery. Studies on survivorship showed up to 76% graft survival at 10 years. Recent studies have suggested a chondroprotective effect, but there is, at present, no evidence to support MAT in the prevention of osteoarthritis. This review article reported the current evidence for MAT showing support for fresh frozen, nonirradiated allografts. However, further research is required to determine the ideal indications for MAT, the optimal graft fixation method, and the safest rehabilitation protocol. Keywords: meniscus, meniscectomy, meniscal allograft transplantation

Gene expression

International Nuclear Information System (INIS)

Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

1983-01-01

We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

Neighboring Genes Show Correlated Evolution in Gene Expression

Science.gov (United States)

Ghanbarian, Avazeh T.; Hurst, Laurence D.

2015-01-01

When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

Gene Expression Commons: an open platform for absolute gene expression profiling.

Directory of Open Access Journals (Sweden)

Jun Seita

Full Text Available Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000 of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/ which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.

MR imaging of meniscal bucket-handle tears: a review of signs and their relation to arthroscopic classification

International Nuclear Information System (INIS)

Aydingoez, Uestuen; Firat, Ahmet K.; Atay, Ahmet Oe.; Doral, Nedim M.

2003-01-01

Our objective was to review the MR imaging signs of meniscal bucket-handle tears and assess the relevance of these signs to the arthroscopic classification of displaced meniscal tears. Forty-five menisci in 42 patients who had a diagnosis of bucket-handle tear either on MR imaging or on subsequent arthroscopy (in which Dandy's classification of meniscal tears was used) were retrospectively analyzed for MR imaging findings of double posterior cruciate ligament (PCL), fragment within the intercondylar notch, absent bow tie, flipped meniscus, double-anterior horn, and disproportional posterior horn signs. Arthroscopy, which was considered as the gold standard, revealed 41 bucket-handle tears (either diagnosed or not diagnosed by MR imaging) in 38 patients (33 males, 5 females). There was a stastistically significant male preponderance for the occurrence of meniscal bucket-handle tears. Overall, sensitivity and positive predictive value of MR imaging for the detection of meniscal bucket-handle tears were calculated as 90%. Common MR imaging signs of meniscal bucket-handle tears in arthroscopically proven cases of such tears were the fragment in the notch and absent bow tie signs (98% frequency for each). Double-PCL, flipped meniscus, double-anterior horn, and disproportional posterior horn signs, however, were less common (32, 29, 29, and 27%, respectively). An arthroscopically proven bucket-handle tear was found in all patients who displayed at least three of the six MR imaging signs of meniscal bucket-handle tears. The presence of three or more MR imaging signs of meniscal bucket-handle tears is highly suggestive of this condition. (orig.)

Isolated medial meniscal tear in a Border Collie.

Science.gov (United States)

Ridge, P A

2006-01-01

A three-year-old, female Border Collie was successfully treated for an isolated, torn, medial meniscus by arthroscopic meniscal tear resection. The dog returned to agility competition without recurrence of lameness.

Large regional differences in incidence of arthroscopic meniscal procedures in the public and private sector in Denmark

DEFF Research Database (Denmark)

Hare, Kristoffer Borbjerg; Vinther, Jesper Høeg; Lohmander, L Stefan

2015-01-01

OBJECTIVES: A recent study reported a large increase in the number of meniscal procedures from 2000 to 2011 in Denmark. We examined the nation-wide distribution of meniscal procedures performed in the private and public sector in Denmark since different incentives may be present and the use...... of these procedures may differ from region to region. SETTING: We included data on all patients who underwent an arthroscopic meniscal procedure performed in the public or private sector in Denmark. PARTICIPANTS: Data were retrieved from the Danish National Patient Register on patients who underwent arthroscopic...... for public and private procedures for each region. RESULTS: Incidence of meniscal procedures increased at private and at public hospitals. The private sector accounted for the largest relative and absolute increase, rising from an incidence of 1 in 2000 to 98 in 2011. In 2011, the incidence of meniscal...

Structural pathology is not related to patient-reported pain and function in patients undergoing meniscal surgery

DEFF Research Database (Denmark)

Christensen, Simon Tornbjerg; Nissen, Nis; Englund, Martin

2017-01-01

BACKGROUND: The relationship between meniscal tears and other joint pathologies with patient-reported symptoms is not clear. We investigated associations between structural knee pathologies identified at surgery with preoperative knee pain and function in patients undergoing arthroscopic meniscal...... of meniscal tears questionnaire, supplemented with information extracted from surgery reports. Following hypothesis-driven preselection of candidate variables, backward elimination regressions were performed to investigate associations between patient-reported outcomes and structural knee pathologies. RESULTS...... surgery. METHODS: This study included 443 patients from the Knee Arthroscopy Cohort Southern Denmark (KACS), a prospective cohort following patients 18 years or older undergoing arthroscopic meniscal surgery at 4 hospitals between 1 February 2013 and 31 January 2014. Patient-reported outcomes, including...

Signs of knee osteoarthritis common in 620 patients undergoing arthroscopic surgery for meniscal tear

DEFF Research Database (Denmark)

Pihl, Kenneth; Englund, Martin; Lohmander, L. Stefan

2017-01-01

Background and purpose - Recent evidence has questioned the effect of arthroscopic knee surgery for middle-aged and older patients with degenerative meniscal tears with or without concomitant radiographic knee osteoarthritis (OA). We investigated the prevalence of early or more established knee OA...... and patients' characteristics in a cohort of patients undergoing arthroscopic surgery for a meniscal tear. Patients and methods - 641 patients assigned for arthroscopy on suspicion of meniscus tear were consecutively recruited from February 2013 through January 2015. Of these, 620 patients (mean age 49 (18...... established knee OA was present in 43% of patients undergoing knee arthroscopy for meniscal tear....

Arthroscopic all-inside meniscal repair - Does the meniscus heal? A clinical and radiological follow-up examination to verify meniscal healing using a 3-T MRI

Energy Technology Data Exchange (ETDEWEB)

Hoffelner, Thomas; Resch, Herbert; Mayer, Michael; Tauber, Mark [Department of Traumatology and Sports Injuries, Salzburg (Austria); Forstner, Rosemarie [University Hospital of Salzburg, Department of Radiology, Salzburg (Austria); Minnich, Bernd [University of Salzburg, Department of Organismic Biology, Salzburg (Austria)

2011-02-15

The purpose of this study was to correlate clinical and radiological results using a 3-T MRI to verify meniscal healing after arthroscopic all-inside meniscus repair. We selected 27 patients (14 men and 13 women) with an average age of 31 {+-} 9 years and retrospective clinical examinations and radiological assessments using a 3-T MRI after all-inside arthroscopic meniscal repair were conducted. Repair of the medial meniscus was performed in 19 patients and of the lateral meniscus in eight. In 17 patients (63%), we performed concomitant anterior cruciate ligament reconstruction. The mean follow-up period was 4.5 {+-} 1.7 years. The Lysholm score and Tegner activity index were used for clinical evaluation. Four grades were used to classify the radiological signal alterations within the meniscus: central globular (grade 1); linear horizontal or band-like (grade 2); intrameniscal alterations and linear signal alterations communicating with the articular surface (grade 3); and complex tears (grade 4). At follow-up, the average Lysholm score was 76 {+-} 15 points, with ten of the patients placed in group 6 based on the Tegner activity index. MRI examinations revealed no signal alteration in three patients, grade 1 in 0, grade 2 in five, grade 3 in 13, and grade 4 in six. The MRI findings correlated positively with the clinical scores in 21 patients (78%). Correlation of clinical and radiological examination was performed using 3-T MRI. In spite of satisfactory clinical outcomes at follow-up, a radiological signal alteration may still be visible on MRI, which was believed to be scar tissue, but could not be proven definitively. Imaging with a 3-Tesla MRI after meniscal suture surgery provides good but no definitive reliability on meniscus healing and therefore gives no advantage compared to 1.5-T MRI, with good clinical outcome using an all-inside arthroscopic meniscal repair. 3T-MRI can not substitute diagnostic arthroscopy in patients with persistent complaints after

Arthroscopic all-inside meniscal repair - Does the meniscus heal? A clinical and radiological follow-up examination to verify meniscal healing using a 3-T MRI

International Nuclear Information System (INIS)

Hoffelner, Thomas; Resch, Herbert; Mayer, Michael; Tauber, Mark; Forstner, Rosemarie; Minnich, Bernd

2011-01-01

The purpose of this study was to correlate clinical and radiological results using a 3-T MRI to verify meniscal healing after arthroscopic all-inside meniscus repair. We selected 27 patients (14 men and 13 women) with an average age of 31 ± 9 years and retrospective clinical examinations and radiological assessments using a 3-T MRI after all-inside arthroscopic meniscal repair were conducted. Repair of the medial meniscus was performed in 19 patients and of the lateral meniscus in eight. In 17 patients (63%), we performed concomitant anterior cruciate ligament reconstruction. The mean follow-up period was 4.5 ± 1.7 years. The Lysholm score and Tegner activity index were used for clinical evaluation. Four grades were used to classify the radiological signal alterations within the meniscus: central globular (grade 1); linear horizontal or band-like (grade 2); intrameniscal alterations and linear signal alterations communicating with the articular surface (grade 3); and complex tears (grade 4). At follow-up, the average Lysholm score was 76 ± 15 points, with ten of the patients placed in group 6 based on the Tegner activity index. MRI examinations revealed no signal alteration in three patients, grade 1 in 0, grade 2 in five, grade 3 in 13, and grade 4 in six. The MRI findings correlated positively with the clinical scores in 21 patients (78%). Correlation of clinical and radiological examination was performed using 3-T MRI. In spite of satisfactory clinical outcomes at follow-up, a radiological signal alteration may still be visible on MRI, which was believed to be scar tissue, but could not be proven definitively. Imaging with a 3-Tesla MRI after meniscal suture surgery provides good but no definitive reliability on meniscus healing and therefore gives no advantage compared to 1.5-T MRI, with good clinical outcome using an all-inside arthroscopic meniscal repair. 3T-MRI can not substitute diagnostic arthroscopy in patients with persistent complaints after

Large regional differences in incidence of arthroscopic meniscal procedures in the public and private sector in Denmark.

Science.gov (United States)

Hare, Kristoffer Borbjerg; Vinther, Jesper Høeg; Lohmander, L Stefan; Thorlund, Jonas Bloch

2015-02-24

A recent study reported a large increase in the number of meniscal procedures from 2000 to 2011 in Denmark. We examined the nation-wide distribution of meniscal procedures performed in the private and public sector in Denmark since different incentives may be present and the use of these procedures may differ from region to region. We included data on all patients who underwent an arthroscopic meniscal procedure performed in the public or private sector in Denmark. Data were retrieved from the Danish National Patient Register on patients who underwent arthroscopic meniscus surgery as a primary or secondary procedure in the years 2000 to 2011. Hospital identification codes enabled linkage of performed procedures to specific hospitals. Yearly incidence of meniscal procedures per 100,000 inhabitants was calculated with 95% CIs for public and private procedures for each region. Incidence of meniscal procedures increased at private and at public hospitals. The private sector accounted for the largest relative and absolute increase, rising from an incidence of 1 in 2000 to 98 in 2011. In 2011, the incidence of meniscal procedures was three times higher in the Capital Region than in Region Zealand. Our study identified a large increase in the use of meniscal procedures in the public and private sector in Denmark. The increase was particularly conspicuous in the private sector as its proportion of procedures performed increased from 1% to 32%. Substantial regional differences were present in the incidence and trend over time of meniscal procedures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Meniscal and cruciate ligaments tears diagnosed with MR imaging versus arthroscopy

International Nuclear Information System (INIS)

Ziemianski, A.; Kruczynski, J.; Bruszewski, J.

1993-01-01

MR studies of knee joints in 37 patients were performed. The clinical diagnostics was traumatic lesions of menisci or cruciate ligaments. Arthroscopy of the knee joint was performed in 21 patients. MR showed meniscal lesion in 25 patients and anterior cruciate ligament (ACL) lesions in 18 patients. Arthroscopy showed meniscal lesions in 16 of 21 patients and ACL lesions in 11 of 21 patients. MR correlated with arthroscopy in 16 of examined menisci and 15 of 21 examined ACL. (author)

Value of modern sonography in the assessment of meniscal lesions

International Nuclear Information System (INIS)

Wareluk, Pawel; Szopinski, Kazimierz T.

2012-01-01

The aim of this prospective study was to assess the accuracy of modern ultrasonography in diagnostic imaging of meniscal tears. One hundred and sixty menisci were evaluated in 80 patients (42 females, 38 males, mean age = 36.2 years, range = 16–70 years). Inclusion criteria for the study were twofold: clinical suspicion of meniscal injury and clinical indication for arthroscopy. Knee examination was performed with the Voluson 730 Expert ultrasound system (General Electric). After sonographic examination, all patients underwent arthroscopic procedures within 1–4 days. The final diagnosis of meniscal tears was taken from surgical reports. The overall sensitivity, specificity, positive predictive value and negative predictive value of sonographic examination in the assessment of meniscal tears amounted to 85.4%, 85.7%, 67.3% and 94.4%, respectively. The statistical parameters were not statistically different in medial and lateral menisci. Age, sex, body mass index (BMI), weight, physical activity, mechanism on injury, and time lapse from injury did not have a statistically significant impact on the usefulness of ultrasonography. The highest sensitivity (>90%) was obtained in medial menisci and in patients with a BMI > 25. The highest specificity (>90%) was obtained in lateral menisci, in patients after twisting injuries, in sports injuries, and in recent injuries (time lapse from the injury <1 month). The positive predictive value (PPV) of sonographic examination was higher than 90% only in recent injuries (<1 month), however, the negative predictive value of ultrasound is high, being less than 90% in males with lesions of lateral menisci and in sequelae of sports injuries

Value of modern sonography in the assessment of meniscal lesions

Energy Technology Data Exchange (ETDEWEB)

Wareluk, Pawel, E-mail: pwareluk@wum.edu.pl [Department of Diagnostic Imaging, Second Faculty of Medicine, Medical University of Warsaw, ul. Kondratowicza 8, 03-242 Warsaw (Poland); Szopinski, Kazimierz T., E-mail: kszopinski@wum.edu.pl [Department of Dental and Maxillofacial Radiology, First Faculty of Medicine, Medical University of Warsaw, ul. Nowogrodzka 59, 02-006 Warsaw (Poland)

2012-09-15

The aim of this prospective study was to assess the accuracy of modern ultrasonography in diagnostic imaging of meniscal tears. One hundred and sixty menisci were evaluated in 80 patients (42 females, 38 males, mean age = 36.2 years, range = 16–70 years). Inclusion criteria for the study were twofold: clinical suspicion of meniscal injury and clinical indication for arthroscopy. Knee examination was performed with the Voluson 730 Expert ultrasound system (General Electric). After sonographic examination, all patients underwent arthroscopic procedures within 1–4 days. The final diagnosis of meniscal tears was taken from surgical reports. The overall sensitivity, specificity, positive predictive value and negative predictive value of sonographic examination in the assessment of meniscal tears amounted to 85.4%, 85.7%, 67.3% and 94.4%, respectively. The statistical parameters were not statistically different in medial and lateral menisci. Age, sex, body mass index (BMI), weight, physical activity, mechanism on injury, and time lapse from injury did not have a statistically significant impact on the usefulness of ultrasonography. The highest sensitivity (>90%) was obtained in medial menisci and in patients with a BMI > 25. The highest specificity (>90%) was obtained in lateral menisci, in patients after twisting injuries, in sports injuries, and in recent injuries (time lapse from the injury <1 month). The positive predictive value (PPV) of sonographic examination was higher than 90% only in recent injuries (<1 month), however, the negative predictive value of ultrasound is high, being less than 90% in males with lesions of lateral menisci and in sequelae of sports injuries.

Imaging gene expression in gene therapy

International Nuclear Information System (INIS)

Wiebe, Leonard I.

1997-01-01

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

Association of MRI findings and expert diagnosis of symptomatic meniscal tear among middle-aged and older adults with knee pain.

Science.gov (United States)

Deshpande, Bhushan R; Losina, Elena; Smith, Savannah R; Martin, Scott D; Wright, R John; Katz, Jeffrey N

2016-04-11

Our aim was to examine the association between an expert clinician's impression of symptomatic meniscal tears and subsequent MRI in the context of middle-aged and older adults with knee pain. Patients older than 45 were eligible for this IRB-approved substudy if they had knee pain, had not undergone MRI and saw one of two orthopaedic surgeons experienced in the diagnosis of meniscal tear. The surgeon rated their confidence that the patient's symptoms were due to meniscal tear. The patient subsequently had a 1.5 or 3.0 T MRI within 6 months. We examined the association between presence of meniscal tear on MRI and the surgeon's confidence that the knee pain was due to meniscal tear using a χ(2) test for trend. Of 84 eligible patients, 63% were female, with a mean age of 64 years and a mean BMI of 27. The surgeon was confident that symptoms emanated from a tear among 39%. The prevalence of meniscal tear on MRI overall was 74%. Among subjects whose surgeon indicated high confidence that symptoms were due to meniscal tear, the prevalence was 80% (95% CI 63-90%). Similarly, the prevalence was 87% (95% CI 62-96%) among those whose surgeon had medium confidence and 64% (95% CI 48-77%) among those whose surgeon had low confidence (p = 0.12). Meniscal tears were frequently found on MRI even when an expert clinician was confident that a patient's knee symptoms were not due to a meniscal tear, indicating that providers should use MRI sparingly and cautiously to confirm or rule out the attribution of knee pain to meniscal tear.

Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data

OpenAIRE

Ezer, Daphne; Moignard, Victoria; G?ttgens, Berthold; Adryan, Boris

2016-01-01

Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete ...

Imaging gene expression in gene therapy

Energy Technology Data Exchange (ETDEWEB)

Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

1997-12-31

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

Usefulness of turbo spin-echo MR imaging in meniscal tears of the knee

International Nuclear Information System (INIS)

Jeong, Gun Young; Choi, Chang Lak; Chung, Jin Young; Han, Tae Il; Jang, Hong Im; Kim, Ji Min; Han, Hyun Young; Song, Mun Kab; Yang, Chang Kyu

1998-01-01

To evaluate the usefulness and diagnostic accuracy of turbo spin-echo(TSE) proton-density and T2-weighted images of meniscal tears of the knee. We retrospectively evaluated the sensitivity, specificity, and accuracy of TSE proton density and T2-weighted images of meniscal tears confirmed arthroscopically or surgically in 47 patients(98 menisci). The routine TSE parameters used in all patients were the dual echo sequence with sagittal proton density and T2-weighed images(4000/16, 90/5/2 [TR/effectiveTE/ETL/NEX]), and fat-suppressed coronal proton density and T2-weighted images. The chi-square test was used for statistical analysis. The sensitivity, specificity, and accuracy of TSE proton density images for the detection of meniscal tears were 93.9%, 93.8%, and 93.9%, respectively, in the medial meniscus, and 92.9%, 91.4%, and 91.8% in the lateral. On T2-weighted images the corresponding figures were 87.9%, 8%, and 89.8%, respectively, in the medial meniscus, and 64.3%, 91.4%, and 83.7% in the lateral. With regard to sensitivity and accuracy, TSE proton density images of meniscal tears were superior to TSE T2-weighted images.=20

MRI diagnosis in meniscal tears: a Meta analysis

International Nuclear Information System (INIS)

Liu Xiaosheng; Xu Jianrong; Hua Jia; Wang Baisong

2007-01-01

Objective: To perform a Meta-analysis to evaluate the overall diagnostic value of magnetic resonance imaging (MRI) in patients with suspected meniscal tears. Methods: All the papers concerning the diagnosis of meniscal tears using MRI in both English and Chinese published from 1998 to 2004 had been searched and reviewed, and the studies with the arthroscopy as the gold standard were adopted as eligible. Statistical analysis was performed employing SAS 8.0. Heterogeneity of the included articles was tested, which was used to select proper effect model to calculate pooled weighted sensitivity, specificity and accuracy. Summary receiver operating characteristic (SROC) analyses were performed for tears of both menisci. Finally, subgroup analysis on magnetic field strength was performed. Results: Totally 11 studies were met the inclusion criteria with a total of 1221 patients. The pooled indexes of diagnostic performance and SROC demonstrated a high discriminatory power for detecting tears of the medial and lateral menisci. The value of TPR * for medial and lateral menisci showed no significant difference (0.90, 0.86, respectively, Z=0.11, P>0.05). Subgroup analysis demonstrated no statistically significant difference on diagnostic performance for various magnetic field strength (P>0.05). Conclusion: MRI is a highly accurate diagnostic tool for detecting tears of the medial and lateral menisci. At present, there is no evidence to ascertain that higher magnetic field strength improves discriminatory power for meniscal tears. (authors)

An anatomical study of normal meniscal roots with isotropic 3D MRI at 3 T

International Nuclear Information System (INIS)

Ren Ahong; Zheng Zhuozhao; Shang Yao; Tian Chunyan

2012-01-01

Objectives: To clarify the morphological features of normal meniscal roots on magnetic resonance (MR) imaging with an isotropic 3D proton density-weighted (PDW) sequence. Materials: 3D PDW MR was performed in sixty-two patients at 3 T before knee arthroscopy. MR images of 34 normal medial menisci and 33 intact lateral menisci confirmed by arthroscopy were retrospectively evaluated. MR signals, insertion sites, dimensions and courses of four meniscal roots were recorded. Results: The anterior root of medial meniscus (ARMM) was typically hypointense, while the posterior root of medial meniscus (PRMM) and the anterior root of lateral meniscus (ARLM) were prone to be hyperintense or showing a comblike signal, and the posterior root of lateral meniscus (PRLM) was usually hypointense or comblike on PDW MR images. ARMM and PRLM had more complex and diverse insertion patterns than ARLM and PRMM. There were significant statistical differences of the lengths, widths, heights and course angles among four meniscal roots (all P < 0.001). Conclusions: The signal intensity of each meniscal root can be hypointense, hyperintense, or comblike on 3D PDW MR images. ARMM and PRLM have more complex and diverse insertion patterns than ARLM and PRMM. The dimensions and courses of four meniscal roots all differ.

Evaluation of meniscal subluxation of the knee with MR imaging

International Nuclear Information System (INIS)

Kim, Hyun Chul; Park, Jin Gyoon; Kang, Heoung Keun; Kim, Jae Kyu; Seo, Jeong Jin; Kim, Yun Hyeon; Chung, Tae Woong

2000-01-01

The purpose of this study was to determine the normal meniscal position and meniscal subluxation by means of MR imaging. The normal position of the meniscus was determined by measuring the distance between the peripheral meniscal borders and the tibial plateau, as seen on coronal, sagittal and oblique MR images of 40 normal knees. For 33 abnormal knees in which outward subluxation of the meniscus from the tibial plateau was noted, the involved site, the predisposing factor, and the frequency of meniscus tearing were analyzed. In normal knees, the peripheral border of the meniscus extruded 3mm or less from the peripheral border of the tibial plateau. Among 33 abnormal knees, in which 5mm or more outward subluxation of the meniscus was seen, 19 menisci were medial and 14 were lateral. Among the 19, the body was involved in 12, the anterior horn in six, and the posterior horn in one. With regard to the 14 lateral subluxations, involvement of the posterior horn occurred in ten, of both the body and posterior horn in two, of the anterior horn in one, and of the body in one. The common predisposing factor in medial meniscus subluxation was osteoarthritis, seen in 89% of such cases, and in lateral subluxation, anterior cruciate ligament tear, which occurred in 79% of cases. Medial meniscus tear was noted in 89% of medial meniscus subluxations and lateral meniscus tear in 43% of lateral subluxations. Meniscal subluxation was easily detected by MR imaging of the knee. The common predisposing factor in medial meniscus subluxation was osteoarthritis, and in lateral meniscus subluxation, anterior cruciate ligament tear. A torn meniscus frequently co-occurred

Longitudinal follow-up of patients with conservatively treated and arthroscopically repaired peripheral meniscal tears

International Nuclear Information System (INIS)

Deutsch, A.L.; Mink, J.H.; Rothman, B.J.

1989-01-01

Tears involving the peripheral third of the meniscus represent an important subgroup of meniscal injuries due to their unique ability to heal by synovial ingrowth and vascular proliferation. Serial MR images were obtained in 14 patients with arthroscopically proved peripheral meniscal tears to assess changes in MR appearance associated with meniscal healing. Six patients were treated conservatively, and eight underwent arthroscopic repair. All patients were considered clinically stable and presumably healed based on commonly accepted orthopedic criteria. Persistent grade 3 signal was seen in all patients up to 6 months after injury. In two patients more than 14 months after repair, grade 3 signal was present but decreased. In no patient did the signal entirely resolve. The authors concluded that signal from conservatively treated and repaired meniscal tears may persist long after the tear has become asymptomatic and presumable healed. This likely reflects known histologic differences between the native meniscus and reparative fibrocartilage. Persistence of grade 3 signal should not be interpreted as reflective of nonhealing in patients with persistent symptoms or as evidence of another tear in those with recurrent symptoms

Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

DEFF Research Database (Denmark)

Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje

2016-01-01

Objective To determine if exercise therapy is superior to arthroscopic partial meniscectomy for knee function in middle aged patients with degenerative meniscal tears. Design Randomised controlled superiority trial. Setting Orthopaedic departments at two public hospitals and two physiotherapy...... clinics in Norway. Participants 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. Interventions 12 week supervised exercise therapy alone or arthroscopic partial....... Our results should encourage clinicians and middle aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option. Trial registration www.clinicaltrials.gov (NCT01002794)....

Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients

DEFF Research Database (Denmark)

Kise, Nina Jullum; Risberg, May Arna; Stensrud, Silje

2016-01-01

OBJECTIVE: To determine if exercise therapy is superior to arthroscopic partial meniscectomy for knee function in middle aged patients with degenerative meniscal tears. DESIGN: Randomised controlled superiority trial. SETTING: Orthopaedic departments at two public hospitals and two physiotherapy...... clinics in Norway. PARTICIPANTS: 140 adults, mean age 49.5 years (range 35.7-59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis. INTERVENTIONS: 12 week supervised exercise therapy alone or arthroscopic partial....... Our results should encourage clinicians and middle aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option.Trial registration www.clinicaltrials.gov (NCT01002794)....

MRI imaging of displaced meniscal tears: Report of a case highlighting new potential pitfalls of the MRI signs

International Nuclear Information System (INIS)

Prasad, Abhishek; Brar, Rahat; Rana, Shaleen

2014-01-01

Magnetic resonance imaging (MRI) has been found to be an excellent imaging tool for meniscal injuries. Various MRI signs have been described to detect displaced meniscal injuries, specifically the bucket-handle tears. Although these signs are quite helpful in diagnosing meniscal tears, various pitfalls have also been reported for these signs. Double anterior cruciate ligament (ACL) sign refers to presence of a linear hypointense soft tissue anterior to the ACL, which represented the flipped bucket-handle tear of the meniscus. Disproportional posterior horn and flipped meniscus signs represent asymmetrically thickened horns of the menisci due to overlying displaced meniscal fragments. We report a case wherein MRI of the knee showed tear and displacement of the medial patellofemoral ligament (MPFL) and vastus medialis complex, medial collateral ligament (MCL), and posterior cruciate ligament (PCL) mimicking these signs. To our knowledge, internally displaced MPFL and MCLs have not been described as mimics for displaced meniscal fragments

Middle-aged patients with an MRI-verified medial meniscal tear report symptoms commonly associated with knee osteoarthritis

DEFF Research Database (Denmark)

Hare, Kristoffer B.; Stefan Lohmander, L.; Kise, Nina Jullum

2017-01-01

Background and purpose — No consensus exists on when to perform arthroscopic partial meniscectomy in patients with a degenerative meniscal tear. Since MRI and clinical tests are not accurate in detecting a symptomatic meniscal lesion, the patient’s symptoms often play a large role when deciding...... when to perform surgery. We determined the prevalence and severity of self-reported knee symptoms in patients eligible for arthroscopic partial meniscectomy due to a degenerative meniscal tear. We investigated whether symptoms commonly considered to be related to meniscus injury were associated...... with early radiographic signs of knee osteoarthritis. Patients and methods — We included individual baseline items from the Knee injury and Osteoarthritis Outcome Score collected in 2 randomized controlled trials evaluating treatment for an MRI-verified degenerative medial meniscal tears in 199 patients aged...

Biological knee reconstruction for combined malalignment, meniscal deficiency, and articular cartilage disease.

Science.gov (United States)

Harris, Joshua D; Hussey, Kristen; Wilson, Hillary; Pilz, Kyle; Gupta, Anil K; Gomoll, Andreas; Cole, Brian J

2015-02-01

The aim of this study was to analyze patient-reported outcomes in those undergoing the triad of simultaneous osteotomy, meniscal transplantation, and articular cartilage repair. Patients undergoing simultaneous meniscal transplantation, distal femoral or proximal tibial osteotomy, and articular cartilage surgery by a single surgeon (B.J.C.) were analyzed. Meniscal transplantation was performed using bone-in-slot techniques. Distal femoral and high tibial osteotomies were performed for valgus and varus malalignment, respectively. Microfracture, autologous chondrocyte implantation, and osteochondral autograft or allograft were performed for articular cartilage disease. Validated patient-reported and surgeon-measured outcomes were collected. Preoperative and postoperative outcomes and medial versus lateral disease were compared using Student t tests. Eighteen participants (mean age, 34 ± 7.8 years; symptomatic patients, 7.4 ± 5.6 years; 2.4 ± 1.0 surgical procedures before study enrollment; mean follow-up, 6.5 ± 3.2 years) were analyzed. Two thirds of participants had medial compartment pathologic conditions and one third had lateral compartment pathologic processes. At final follow-up, there were statistically significant clinically meaningful improvements in International Knee Documentation Committee (IKDC) subjective classification, Lysholm score, and 4 Knee Injury and Osteoarthritis Outcome Score (KOOS) subscores. Postoperative 12-item short form (SF-12) physical and mental component scores were not significantly different from preoperative scores. The Kellgren-Lawrence classification grade was 1.5 ± 1.1 at 2.5 ± 3.0 years after surgery. There was a significantly higher preoperative SF-12 physical composite score (PCS) in participants with lateral compartment pathologic conditions (v medial compartment conditions) (P = .011). Although there were 13 reoperations in 10 patients (55.5% reoperation rate), only one patient was converted to knee arthroplasty (5

Meniscal tears: comparison of half-Fourier technique and conventional MR imaging

International Nuclear Information System (INIS)

Shabana, Wael; Maeseneer, Michel de; Machiels, Freddy; Ridder, Filip de; Osteaux, Michel

2003-01-01

Purpose: To determine whether half-Fourier MR image acquisition technique can provide similar information to that of conventional MR acquisition technique for evaluation of meniscal tears. Materials and methods: We studied 101 menisci in 52 patients who were referred for evaluation of meniscal tears. Sagittal MR images of the knee were obtained for all patients by using proton density and T2-weighted SE sequences on a 1-T clinical system. The half-Fourier technique and conventional technique were used for all patients. All other imaging parameters were identical for both sequences (TR/TE=2400/20,70; 3 mm slice thickness; 200x256 matrix; field of view, 200; one signal acquired). Both sets of images were filmed with standard window and level settings. Images were randomised and interpreted independently by two radiologists for the presence of meniscal tears. Images were also subjectively assessed for image quality using a five-point grading scale. Results: On half-Fourier images, Reader 1 interpreted 23 menisci as torn, compared to 28 for Reader 2. On conventional images, Reader 1 interpreted 24 menisci as torn, compared to 26 for Reader 2. Agreement between interpretation of the conventional and that of the half-Fourier images was 99% for Reader 1, and 98% for Reader 2. Agreement between readers for the half-Fourier images was 95%, and for the conventional images 96%. No statistically significant difference was found in the subjective evaluation of image quality between the conventional and half-Fourier images. Conclusion: The half-Fourier acquisition technique compares favourably with the conventional technique for the evaluation of meniscal tears

Trajectory of self-reported pain and function and knee extensor muscle strength in young patients undergoing arthroscopic surgery for meniscal tears

DEFF Research Database (Denmark)

Thorlund, Jonas Bloch; Østengaard, Lasse; Cardy, Nathan

2017-01-01

. PATIENTS AND INTERVENTION: People aged 30 years or younger undergoing surgery for a meniscal tear. OUTCOMES: and comparator: (1) Self-reported pain and function in patients undergoing meniscal surgery compared to a non-operative control group (2). Knee extensor strength in the leg undergoing surgery...... the trajectory of self-reported pain and function in patients undergoing arthroscopic surgery compared with non-operative treatments for young patients with meniscal tears. Knee extensor strength seemed to be impaired up to 12 months after surgery in young patients undergoing surgery for meniscal tears...

FARO server: Meta-analysis of gene expression by matching gene expression signatures to a compendium of public gene expression data

DEFF Research Database (Denmark)

Manijak, Mieszko P.; Nielsen, Henrik Bjørn

2011-01-01

circumvented by instead matching gene expression signatures to signatures of other experiments. FINDINGS: To facilitate this we present the Functional Association Response by Overlap (FARO) server, that match input signatures to a compendium of 242 gene expression signatures, extracted from more than 1700...... Arabidopsis microarray experiments. CONCLUSIONS: Hereby we present a publicly available tool for robust characterization of Arabidopsis gene expression experiments which can point to similar experimental factors in other experiments. The server is available at http://www.cbs.dtu.dk/services/faro/....

Digital gene expression analysis of gene expression differences within Brassica diploids and allopolyploids.

Science.gov (United States)

Jiang, Jinjin; Wang, Yue; Zhu, Bao; Fang, Tingting; Fang, Yujie; Wang, Youping

2015-01-27

Brassica includes many successfully cultivated crop species of polyploid origin, either by ancestral genome triplication or by hybridization between two diploid progenitors, displaying complex repetitive sequences and transposons. The U's triangle, which consists of three diploids and three amphidiploids, is optimal for the analysis of complicated genomes after polyploidization. Next-generation sequencing enables the transcriptome profiling of polyploids on a global scale. We examined the gene expression patterns of three diploids (Brassica rapa, B. nigra, and B. oleracea) and three amphidiploids (B. napus, B. juncea, and B. carinata) via digital gene expression analysis. In total, the libraries generated between 5.7 and 6.1 million raw reads, and the clean tags of each library were mapped to 18547-21995 genes of B. rapa genome. The unambiguous tag-mapped genes in the libraries were compared. Moreover, the majority of differentially expressed genes (DEGs) were explored among diploids as well as between diploids and amphidiploids. Gene ontological analysis was performed to functionally categorize these DEGs into different classes. The Kyoto Encyclopedia of Genes and Genomes analysis was performed to assign these DEGs into approximately 120 pathways, among which the metabolic pathway, biosynthesis of secondary metabolites, and peroxisomal pathway were enriched. The non-additive genes in Brassica amphidiploids were analyzed, and the results indicated that orthologous genes in polyploids are frequently expressed in a non-additive pattern. Methyltransferase genes showed differential expression pattern in Brassica species. Our results provided an understanding of the transcriptome complexity of natural Brassica species. The gene expression changes in diploids and allopolyploids may help elucidate the morphological and physiological differences among Brassica species.

A biomechanical evaluation of all-inside 2-stitch meniscal repair devices with matched inside-out suture repair.

Science.gov (United States)

Ramappa, Arun J; Chen, Alvin; Hertz, Benjamin; Wexler, Michael; Grimaldi Bournissaint, Leandro; DeAngelis, Joseph P; Nazarian, Ara

2014-01-01

Many all-inside suture-based devices are currently available, including the Meniscal Cinch, FasT-Fix, Ultra FasT-Fix, RapidLoc, MaxFire, and CrossFix System. These different devices have been compared in various configurations, but to our knowledge, the Sequent meniscal repair device, which applies running sutures, has not been compared with the Ultra FasT-Fix, nor has it been compared with its suture, No. 0 Hi-Fi, using an inside-out repair technique. To assess the quality of the meniscal repair, all new devices should be compared with the gold standard: the inside-out repair. To that end, this study aims to compare the biomechanical characteristics of running sutures delivered by the Sequent meniscal repair device with 2 vertical mattress sutures applied using the Ultra FasT-Fix device and with 2 vertical mattress sutures using an inside-out repair technique with No. 0 Hi-Fi suture. Controlled laboratory study. Paired (medial and lateral), fresh-frozen porcine menisci were randomly assigned to 1 of 3 groups: Sequent (n = 17), Ultra FasT-Fix (n = 19), and No. 0 Hi-Fi inside-out repair (n = 20). Bucket-handle tears were created in all menisci and were subjected to repair according to their grouping. Once repaired, the specimens were subjected to cyclic loading (100, 300, and 500 cycles), followed by loading to failure. The Sequent and Ultra FasT-Fix device repairs and the suture repair exhibited low initial displacements. The Sequent meniscal repair device demonstrated the lowest displacement in response to cyclic loading. No. 0 Hi-Fi suture yielded the highest load to failure. With the development of the next generation of all-inside meniscal repair devices, surgeons may use these findings to select the method best suited for their patients. The Sequent meniscal repair device displays the least amount of displacement during cyclic loading but has a similar failure load to other devices.

Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

Science.gov (United States)

Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

2014-05-01

Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Meniscal position on routine MR imaging of the knee

International Nuclear Information System (INIS)

Miller, T.T.; Staron, R.B.; Feldman, F.; Cepel, E.

1997-01-01

Objective. To determine the prevalence of meniscal protrusion (i.e. location of the outer edge of a meniscus beyond the tibial articular surface), and to determine its relationship with internal derangement, joint effusion, and degenerative arthropathy. Design and patients. Sagittal and coronal MR images of 111 abnormal and 46 normal knees were evaluated for the presence of meniscal protrusion. We set 25% as the minimum amount of displacement considered abnormal because this was the smallest amount of displacement we could confidently discern. Presence of meniscal tear, anterior cruciate ligament (ACL) injury, joint effusion, or osteophytosis was also recorded. Results and conclusion. Normal examinations demonstrated protrusion of the medial meniscus in 6.5% of sagittal images and 15% of coronal images, and of the lateral meniscus in 2% and 13%, respectively. Fisher's exact test demonstrated a statistically significant difference between the normal and abnormal groups for the medial meniscus on both sagittal (P 0.2). A protruding medial meniscus was associated with effusion and osteophytosis (P 0.1). Posterior protrusion of the lateral meniscus was only associated with ACL injury (P<0.0001); protruding anterior horns and bodies of lateral menisci were not associated with any of the four abnormalities. It is concluded that the medial meniscus may occasionally protrude more than 25% of its width, but protrusion is more often due to effusion and osteophytes. Protrusion of the posterior horn of the lateral meniscus is associated with ACL insufficiency, while protrusion of the body and anterior horn of the lateral meniscus is a normal variant. (orig.). With 4 figs

Comparison of CT and MRI in patients with tibial plateau fracture: can CT findings predict ligament tear or meniscal injury?

International Nuclear Information System (INIS)

Mui, Leonora W.; Engelsohn, Eliyahu; Umans, Hilary

2007-01-01

(1) To determine the accuracy of computed tomography (CT) in the evaluation of ligament tear and avulsion in patients with tibial plateau fracture. (2) To evaluate whether the presence or severity of fracture gap and articular depression can predict meniscal injury. A fellowship-trained musculoskeletal radiologist retrospectively reviewed knee CT and MRI examinations of 41 consecutive patients presenting to a level 1 trauma center with tibial plateau fractures. Fracture gap, articular depression, ligament tear and footprint avulsions were assessed on CT examinations. The MRI studies were examined for osseous and soft tissue injuries, including meniscal tear, meniscal displacement, ligament tear, and ligament avulsion. CT demonstrated torn ligaments with 80% sensitivity and 98% specificity. Only 2% of ligaments deemed intact on careful CT evaluation had partial or complete tears on MRI. Although the degree of fracture gap and articular depression was significantly greater in patients with meniscal injury compared with those without meniscal injury, ROC analysis demonstrated no clear threshold for gap or depression that yielded a combination of high sensitivity and specificity. In the acute setting, CT offers high sensitivity and specificity for depicting osseous avulsions, as well as high negative predictive value for excluding ligament injury. However, MRI remains necessary for the preoperative detection of meniscal injury. (orig.)

The association between reduced knee joint proprioception and medial meniscal abnormalities using MRI in knee osteoarthritis: results from the Amsterdam osteoarthritis cohort.

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van der Esch, M; Knoop, J; Hunter, D J; Klein, J-P; van der Leeden, M; Knol, D L; Reiding, D; Voorneman, R E; Gerritsen, M; Roorda, L D; Lems, W F; Dekker, J

2013-05-01

Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly prevalent in knee OA, have been suggested to play an important role. No study has focussed on the association between proprioceptive accuracy and meniscal abnormalities in knee OA. To explore the association between reduced proprioceptive accuracy and medial meniscal abnormalities in a clinical sample of knee OA subjects. Cross-sectional study in 105 subjects with knee OA. Knee proprioceptive accuracy was assessed by determining the joint motion detection threshold in the knee extension direction. The knee was imaged with a 3.0 T magnetic resonance (MR) scanner. Number of regions with medial meniscal abnormalities and the extent of abnormality in the anterior and posterior horn and body were scored according to the Boston-Leeds Osteoarthritis Knee Score (BLOKS) method. Multiple regression analyzes were used to examine whether reduced proprioceptive accuracy was associated with medial meniscal abnormalities in knee OA subjects. Mean proprioceptive accuracy was 2.9° ± 1.9°. Magnetic resonance imaging (MRI)-detected medial meniscal abnormalities were found in the anterior horn (78%), body (80%) and posterior horn (90%). Reduced proprioceptive accuracy was associated with both the number of regions with meniscal abnormalities (P knee complaints. This is the first study showing that reduced proprioceptive accuracy is associated with medial meniscal abnormalities in knee OA. The study highlights the importance of meniscal abnormalities in understanding reduced proprioceptive accuracy in persons with knee OA. Copyright © 2013 Osteoarthritis Research Society International. All rights reserved.

Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

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Benjamin Mayne

2016-10-01

Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

[SPECIFIC DIAGNOSTIC SIGNIFICANCE OF "RIPPLE SIGN" OF MEDIAL FEMORAL CONDYLE UNDER ARTHROSCOPE IN MEDIAL LONGITUDINAL MENISCAL TEARS].

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Ren Shiyou; Sun, Limang; Chen, Guofei; Jiang, Changqing; Zhang, Xintao; Zhang Wentao

2015-01-01

To investigate the reliability of the "ripple sign" on the upper surface of the medial femoral condyle in the diagnosis of medial longitudinal meniscal tears under arthroscope. Between June 2013 and June 2014, 56 patients with knee injuries were included. There were 35 males and 21 females with an average age of 22.2 years (range, 12-38 years). The causes of injury were sports in 40 cases, falling in 10 cases, and traffic accident in 6 cases. The injury was located at the left knee in 22 cases and at the right knee in 34 cases. The disease duration was 10-40 days (mean, 20.2 days). Of 56 patients, 15 cases had simple medial meniscal injury; 41 cases had combined injuries, including anterior cruciate ligament injury in 38 cases, posterior cruciate ligament injury in 2 cases, and patellar dislocation in 1 case. The "ripple sign" was observed under arthroscope before operation. Repair of medial meniscal injury and reconstruction of cruciate ligament were performed. The positive "ripple sign" was seen under arthroscope in all patients, who were diagnosed to have longitudinal meniscal tears, including 23 cases of mild "ripple sign" , 28 cases of moderate "ripple sign", and 5 cases of severe "ripple sign". The "ripple sign" on the upper surface of the medial femoral condyle is a reliable diagnostic evidence of medial longitudinal meniscal tears.

Differential Gene Expression and Aging

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Laurent Seroude

2002-01-01

Full Text Available It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.

Polycistronic gene expression in Aspergillus niger.

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Schuetze, Tabea; Meyer, Vera

2017-09-25

Genome mining approaches predict dozens of biosynthetic gene clusters in each of the filamentous fungal genomes sequenced so far. However, the majority of these gene clusters still remain cryptic because they are not expressed in their natural host. Simultaneous expression of all genes belonging to a biosynthetic pathway in a heterologous host is one approach to activate biosynthetic gene clusters and to screen the metabolites produced for bioactivities. Polycistronic expression of all pathway genes under control of a single and tunable promoter would be the method of choice, as this does not only simplify cloning procedures, but also offers control on timing and strength of expression. However, polycistronic gene expression is a feature not commonly found in eukaryotic host systems, such as Aspergillus niger. In this study, we tested the suitability of the viral P2A peptide for co-expression of three genes in A. niger. Two genes descend from Fusarium oxysporum and are essential to produce the secondary metabolite enniatin (esyn1, ekivR). The third gene (luc) encodes the reporter luciferase which was included to study position effects. Expression of the polycistronic gene cassette was put under control of the Tet-On system to ensure tunable gene expression in A. niger. In total, three polycistronic expression cassettes which differed in the position of luc were constructed and targeted to the pyrG locus in A. niger. This allowed direct comparison of the luciferase activity based on the position of the luciferase gene. Doxycycline-mediated induction of the Tet-On expression cassettes resulted in the production of one long polycistronic mRNA as proven by Northern analyses, and ensured comparable production of enniatin in all three strains. Notably, gene position within the polycistronic expression cassette matters, as, luciferase activity was lowest at position one and had a comparable activity at positions two and three. The P2A peptide can be used to express at

A Cohort Study on Meniscal Lesions among Airport Baggage Handlers

DEFF Research Database (Denmark)

Mikkelsen, Sigurd; Brauer, Charlotte; Pedersen, Ellen Bøtker

2016-01-01

socioeconomic background and less knee-straining work. Baggage handlers lifted suitcases with an average weight of approximately 15 kg, in total approximately five tonnes during a 9-hour workday. The cohort was followed in the National Patient Register and Civil Registration System. The outcome was a first time......Meniscal lesions are common and may contribute to the development of knee arthrosis. A few case-control and cross-sectional studies have identified knee-straining work as risk factors for meniscal lesions, but exposure-response relations and the role of specific exposures are uncertain...... of unskilled men employed at Copenhagen Airport or in other companies in the metropolitan Copenhagen area from 1990 to 2012 (the Copenhagen Airport Cohort). The cohort at risk included 3,307 airport baggage handlers with heavy lifting and kneeling or squatting work tasks and 63,934 referents with a similar...

Human meniscal proteoglycan metabolism in long-term tissue culture

NARCIS (Netherlands)

Verbruggen, G.; Verdonk, R.; Veys, E. M.; van Daele, P.; de Smet, P.; van den Abbeele, K.; Claus, B.; Baeten, D.

1996-01-01

For the purpose of human meniscal allografting, menisci have been maintained viable in in vitro culture. The influence of long-term tissue culture on the extracellular matrix metabolism of the meniscus has been studied. Fetal calf serum (FCS) was used as a supplement for the growth factors necessary

Meniscectomy versus meniscal repair: 10 years radiological and clinical results in vertical lesions in stable knee.

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Lutz, C; Dalmay, F; Ehkirch, F P; Cucurulo, T; Laporte, C; Le Henaff, G; Potel, J F; Pujol, N; Rochcongar, G; Salledechou, E; Seil, R; Gunepin, F-X; Sonnery-Cottet, B

2015-12-01

Surgical management of meniscal lesion consists of either a meniscectomy or meniscal repair. Although repair offers immediate recovery after surgery, it is also associated with higher rates of revision. A meniscectomy, on the other hand is known to be associated with an early onset of osteoarthritis. The present study compared clinical and radiological results at 10 years between meniscectomy and meniscal repair in isolated vertical lesion in an otherwise stable knee. The hypothesis was that repair shows functional and radiological benefit over meniscectomy. A multi-centric retrospective comparative study of 32 patients (24 male, 8 female). Mean follow-up was 10.6 years (range, 10-13 years). There were 10 meniscal repairs (group R) and 22 meniscectomies (group M), in 17 right and 15 left knees. Mean age at surgery was 33.45±12.3 years (range, 9-47 years). There were 28 medial and 4 lateral meniscal lesions; 26 were in the red-red zone and 6 in red-white zone. Functional score: KOOS score was significantly higher in group R than M on almost all parameters: 98±4.69 versus 77.38±21.97 for symptoms (P=0.0043), 96.89±7.20 versus 78.57±18.9 for pain (P=0.0052), 99.89±0.33 versus 80.88±19.6 for daily life activities (P=0.0002), 96.11±9.83 versus 54.05±32.85 for sport and leisure (P=0.0005), but 91±16.87 versus 68.15±37.7 for quality of life (P=0.1048). Radiology score: in group R, 7 patients had no features of osteoarthritis, and 2 had grade 1 osteoarthritis. In group M, 5 patients had grade 1 osteoarthritis, 10 grade 2, 3 grade 3 and 3 grade 4. Mean quantitative score was 0 (mean, 0.22±0.44) in-group R and 2 (mean, 2.19±0.98) in group M (P<0.0001). At more than 10year's follow-up, functional scores were significantly better with meniscal repair than meniscectomy on all parameters of the KOOS scale except quality of life. Functional and radiological scores correlated closely. These results show that meniscal repair for vertical lesions in stable knees

Gene expression inference with deep learning.

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Chen, Yifei; Li, Yi; Narayan, Rajiv; Subramanian, Aravind; Xie, Xiaohui

2016-06-15

Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. D-GEX is available at https://github.com/uci-cbcl/D-GEX CONTACT: xhx@ics.uci.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Reliability and Validity of the IKDC, KOOS, and WOMAC for Patients With Meniscal Injuries.

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van de Graaf, Victor A; Wolterbeek, Nienke; Scholtes, Vanessa A B; Mutsaerts, Eduard L A R; Poolman, Rudolf W

2014-06-01

Several patient-reported outcome measurements are used to measure functional outcome after treatment of meniscal injuries. However, for comparison of study results, there is a need for a uniform and standardized approach of measuring functional outcome. Selection of the instrument should be based on the quality of its measurement properties, and only the best instrument can be justified to be used. This study aimed to determine and compare the measurement properties of the Dutch-language versions of the International Knee Documentation Committee (IKDC) Subjective Knee Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) in a homogeneous group of patients with meniscal tears. Cohort study (design); Level of evidence, 2. Patients on the waiting list for meniscal surgery and patients between 6 weeks and 6 months after meniscal surgery were included (n = 75). Patients were excluded if they received an arthroplasty or had surgery on the anterior cruciate ligament. Internal consistency (Cronbach alpha), test-retest reliability (intraclass correlation coefficient [ICC]), measurement error (SEM), smallest detectable difference (SDD), content validity, construct validity (factor analysis and hypothesis testing), and floor and ceiling effects were determined. Results for the IKDC, KOOS dimensions, and WOMAC dimensions, respectively, were as follows: Cronbach alpha = .90, .72-.95, and .84-.95; ICC = 0.93, 0.84-0.89, and 0.77-0.89; SEM = 5.3, 7.0-12.6, and 7.3-12.2; SDD = 14.6, 19.4-35.0, and 20.2-33.9; hypotheses testing confirmation = 100%, 86%, and 85%. Floor effects within the SDD from the minimum score were found for the KOOS Sports/Recreation and Quality of Life dimensions. Ceiling effects within the SDD from the maximum score were found for the KOOS Activities of Daily Living and for all WOMAC dimensions. The IKDC showed the best performance on all measurement properties, implying that the IKDC

Scaling of gene expression data allowing the comparison of different gene expression platforms

NARCIS (Netherlands)

van Ruissen, Fred; Schaaf, Gerben J.; Kool, Marcel; Baas, Frank; Ruijter, Jan M.

2008-01-01

Serial analysis of gene expression (SAGE) and microarrays have found a widespread application, but much ambiguity exists regarding the amalgamation of the data resulting from these technologies. Cross-platform utilization of gene expression data from the SAGE and microarray technology could reduce

cis sequence effects on gene expression

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Jacobs Kevin

2007-08-01

Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

Extracting gene expression patterns and identifying co-expressed genes from microarray data reveals biologically responsive processes

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Paules Richard S

2007-11-01

Full Text Available Abstract Background A common observation in the analysis of gene expression data is that many genes display similarity in their expression patterns and therefore appear to be co-regulated. However, the variation associated with microarray data and the complexity of the experimental designs make the acquisition of co-expressed genes a challenge. We developed a novel method for Extracting microarray gene expression Patterns and Identifying co-expressed Genes, designated as EPIG. The approach utilizes the underlying structure of gene expression data to extract patterns and identify co-expressed genes that are responsive to experimental conditions. Results Through evaluation of the correlations among profiles, the magnitude of variation in gene expression profiles, and profile signal-to-noise ratio's, EPIG extracts a set of patterns representing co-expressed genes. The method is shown to work well with a simulated data set and microarray data obtained from time-series studies of dauer recovery and L1 starvation in C. elegans and after ultraviolet (UV or ionizing radiation (IR-induced DNA damage in diploid human fibroblasts. With the simulated data set, EPIG extracted the appropriate number of patterns which were more stable and homogeneous than the set of patterns that were determined using the CLICK or CAST clustering algorithms. However, CLICK performed better than EPIG and CAST with respect to the average correlation between clusters/patterns of the simulated data. With real biological data, EPIG extracted more dauer-specific patterns than CLICK. Furthermore, analysis of the IR/UV data revealed 18 unique patterns and 2661 genes out of approximately 17,000 that were identified as significantly expressed and categorized to the patterns by EPIG. The time-dependent patterns displayed similar and dissimilar responses between IR and UV treatments. Gene Ontology analysis applied to each pattern-related subset of co-expressed genes revealed underlying

What is the best way to fix a polyurethane meniscal scaffold? A biomechanical evaluation of different fixation modes.

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Hardeman, Francois; Corten, Kristoff; Mylle, Michiel; Van Herck, Bert; Verdonk, René; Verdonk, Peter; Bellemans, Johan

2015-01-01

Ingrowth of meniscal tissue into a meniscal scaffold can be optimized by securely fixing the scaffold into the meniscal remnants. The purpose of this research was to test and compare commonly used suture types and suture materials to fix a meniscal scaffold. Forty fresh porcine menisci were used. All tests used the same polyurethane-based scaffold. The load to failure of horizontal, vertical and diagonal sutures with PDS 0 and with Ethibond 0, and diagonal sutures with Ultra Fast-Fix(®) and Sequent(®) to fix a meniscal scaffold were tested. Five tests were conducted for each configuration. All constructs failed in the scaffold at a mean pullout force of 50.6 N (SD 12.7). Inferior results were noted for vertical sutures (40.1 N, SD 6.3) compared to horizontal (49.8 N, SD 5.5, p = 0.0007) and diagonal (51.7 N, SD 15.6, p = 0.024) sutures and for Ethibond 0 (41.4 N, SD 6.2) compared to PDS 0 (51.3 N, SD 12.9, p = 0.001). When comparing the diagonal suture placements, only Ethibond 0 (42.9 N, SD 5.4) showed significantly inferior results compared to PDS 0 (60.1 N, SD 16.9, p = 0.03), Ultra Fast-Fix(®) (60.1 N, SD 9.3, p = 0.004) and Sequent(®) (65.8 N, SD 4.4, p < 0.0001). The most common failure mode when fixing a polyurethane-based meniscal scaffold is suture pull-through of the scaffold in the distraction mode. This happens at a rather low pullout force and might preclude the use of this scaffold clinically. Vertical sutures and Ethibond 0 multifilament braided sutures fail at lower forces, and the tested commercial devices show promising results.

Occupational kneeling and meniscal tears: a magnetic resonance imaging study in floor layers

DEFF Research Database (Denmark)

Rytter, Søren; Jensen, Lilli Kirkeskov; Bonde, Jens Peter

2009-01-01

OBJECTIVE: To evaluate the association between occupational kneeling and degenerative meniscal tears. METHODS: Magnetic resonance imaging (MRI) of both knees was conducted in 92 male floor layers and 49 male graphic designers (referents), with a mean age of 55.6 years (range 42-70 yrs). The prese......OBJECTIVE: To evaluate the association between occupational kneeling and degenerative meniscal tears. METHODS: Magnetic resonance imaging (MRI) of both knees was conducted in 92 male floor layers and 49 male graphic designers (referents), with a mean age of 55.6 years (range 42-70 yrs......). The presence of grade 3 MRI signal intensities indicating degenerative tears of the anterior, middle, and posterior one-third of the lateral and medial menisci was assessed on 1.5-Tesla MRI scans. The odds ratio (OR) of meniscal tears was determined among floor layers compared to graphic designers. Using...... logistic regression, models were adjusted for age, body mass index, and knee-straining sports. RESULTS: Degenerative tears were significantly more prevalent in the medial meniscus among floor layers than among graphic designers [OR 2.28, 95% confidence interval (CI) 1.10-4.98] and significantly more floor...

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

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Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

Science.gov (United States)

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

Comparison of osmotic swelling influences on meniscal fibrocartilage and articular cartilage tissue mechanics in compression and shear.

Science.gov (United States)

Nguyen, An M; Levenston, Marc E

2012-01-01

Although the contribution of the circumferential collagen bundles to the anisotropic tensile stiffness of meniscal tissue has been well described, the implications of interactions between tissue components for other mechanical properties have not been as widely examined. This study compared the effects of the proteoglycan-associated osmotic swelling stress on meniscal fibrocartilage and articular cartilage (AC) mechanics by manipulating the osmotic environment and tissue compressive offset. Cylindrical samples were obtained from the menisci and AC of bovine stifles, equilibrated in phosphate-buffered saline solutions ranging from 0.1× to 10×, and tested in oscillatory torsional shear and unconfined compression. Biochemical analysis indicated that treatments and testing did not substantially alter tissue composition. Mechanical testing revealed tissue-specific responses to both increasing compressive offset and decreasing bath salinity. Most notably, reduced salinity dramatically increased the shear modulus of both axially and circumferentially oriented meniscal tissue explants to a much greater extent than for cartilage samples. Combined with previous studies, these findings suggest that meniscal proteoglycans have a distinct structural role, stabilizing, and stiffening the matrix surrounding the primary circumferential collagen bundles. Copyright © 2011 Orthopaedic Research Society.

Modulation of gene expression made easy

DEFF Research Database (Denmark)

Solem, Christian; Jensen, Peter Ruhdal

2002-01-01

A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

Performance of PROMIS for Healthy Patients Undergoing Meniscal Surgery.

Science.gov (United States)

Hancock, Kyle J; Glass, Natalie; Anthony, Chris A; Hettrich, Carolyn M; Albright, John; Amendola, Annunziato; Wolf, Brian R; Bollier, Matthew

2017-06-07

The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed as an extensive question bank with multiple health domains that could be utilized for computerized adaptive testing (CAT). In the present study, we investigated the use of the PROMIS Physical Function CAT (PROMIS PF CAT) in an otherwise healthy population scheduled to undergo surgery for meniscal injury with the hypotheses that (1) the PROMIS PF CAT would correlate strongly with patient-reported outcome instruments that measure physical function and would not correlate strongly with those that measure other health domains, (2) there would be no ceiling effects, and (3) the test burden would be significantly less than that of the traditional measures. Patients scheduled to undergo meniscal surgery completed the PROMIS PF CAT, Knee injury and Osteoarthritis Outcome Score (KOOS), Marx Knee Activity Rating Scale, Short Form-36 (SF-36), and EuroQol-5 Dimension (EQ-5D) questionnaires. Correlations were defined as high (≥0.7), high-moderate (0.61 to 0.69), moderate (0.4 to 0.6), moderate-weak (0.31 to 0.39), or weak (≤0.3). If ≥15% respondents to a patient-reported outcome measure obtained the highest or lowest possible score, the instrument was determined to have a significant ceiling or floor effect. A total of 107 participants were analyzed. The PROMIS PF CAT had a high correlation with the SF-36 Physical Functioning (PF) (r = 0.82, p ceiling effects, with 0% of the participants achieving the lowest and highest score, respectively. The PROMIS PF CAT correlates strongly with currently used patient-reported outcome measures of physical function and demonstrates no ceiling effects for patients with meniscal injury requiring surgery. It may be a reasonable alternative to more burdensome patient-reported outcome measures.

Using gene expression noise to understand gene regulation

NARCIS (Netherlands)

Munsky, B.; Neuert, G.; van Oudenaarden, A.

2012-01-01

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus.

Science.gov (United States)

Cucchiarini, M; McNulty, A L; Mauck, R L; Setton, L A; Guilak, F; Madry, H

2016-08-01

Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis (OA). Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The role of meniscal tissue in joint protection in early osteoarthritis.

Science.gov (United States)

Verdonk, Rene; Madry, Henning; Shabshin, Nogah; Dirisamer, Florian; Peretti, Giuseppe M; Pujol, Nicolas; Spalding, Tim; Verdonk, Peter; Seil, Romain; Condello, Vincenzo; Di Matteo, Berardo; Zellner, Johannes; Angele, Peter

2016-06-01

It is widely accepted that partial meniscectomy leads to early onset of osteoarthritis (OA). A strong correlation exists between the amount and location of the resected meniscus and the development of degenerative changes in the knee. On the other hand, osteoarthritic changes of the joint alter the structural and functional integrity of meniscal tissue. These alterations might additionally compromise the limited healing capacity of the meniscus. In young, active patients without cartilage damage, meniscus therapy including partial meniscectomy, meniscus suture, and meniscus replacement has proven beneficial effects in long-term studies. Even in an early osteoarthritic milieu, there is a relevant regenerative potential of the meniscus and the surrounding cartilage. This potential should be taken into account, and meniscal surgery can be performed with the correct timing and the proper indication even in the presence of early OA.

Implantation of autogenous meniscal fragments wrapped with a fascia sheath enhances fibrocartilage regeneration in vivo in a large harvest site defect.

Science.gov (United States)

Kobayashi, Yasukazu; Yasuda, Kazunori; Kondo, Eiji; Katsura, Taro; Tanabe, Yoshie; Kimura, Masashi; Tohyama, Harukazu

2010-04-01

Concerning meniscal tissue regeneration, many investigators have studied the development of a tissue-engineered meniscus. However, the utility still remains unknown. Implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect may significantly enhance fibrocartilage regeneration in vivo in the defect. Controlled laboratory study. Seventy-five mature rabbits were used in this study. In each animal, an anterior one-third of the right medial meniscus was resected. Then, the animals were divided into the following 3 groups of 25 rabbits each: In group 1, no treatment was applied to the meniscal defect. In group 2, the defect was covered with a fascia sheath. In group 3, after the resected meniscus was fragmented into small pieces, the fragments were grafted into the defect. Then, the defect with the meniscal fragments was covered with a fascia sheath. In each group, 5 rabbits were used for histological evaluation at 3, 6, and 12 weeks after surgery, and 5 rabbits were used for biomechanical evaluation at 6 and 12 weeks after surgery. Histologically, large round cells in group 3 were scattered in the core portion of the meniscus-shaped tissue, and the matrix around these cells was positively stained by safranin O and toluisin blue at 12 weeks. The histological score of group 3 was significantly higher than that of group 1 and group 2. Biomechanically, the maximal load and stiffness of group 3 were significantly greater than those of groups 1 and 2. This study clearly demonstrated that implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect significantly enhanced fibrocartilage regeneration in vivo in the defect at 12 weeks after implantation in the rabbit. This study proposed a novel strategy to treat a large defect after a meniscectomy.

A Cohort Study on Meniscal Lesions among Airport Baggage Handlers

DEFF Research Database (Denmark)

Mikkelsen, Sigurd; Brauer, Charlotte; Pedersen, Ellen Bøtker

2016-01-01

and then decreased slowly to reach unity after approximately 30 years, adjusted for effects of potential confounders. This relation between baggage handling and meniscal lesions was present for work on the apron which involves lifting in a kneeling or squatting position, but not in the baggage hall, which only...

Characterization of differentially expressed genes using high-dimensional co-expression networks

DEFF Research Database (Denmark)

Coelho Goncalves de Abreu, Gabriel; Labouriau, Rodrigo S.

2010-01-01

We present a technique to characterize differentially expressed genes in terms of their position in a high-dimensional co-expression network. The set-up of Gaussian graphical models is used to construct representations of the co-expression network in such a way that redundancy and the propagation...... that allow to make effective inference in problems with high degree of complexity (e.g. several thousands of genes) and small number of observations (e.g. 10-100) as typically occurs in high throughput gene expression studies. Taking advantage of the internal structure of decomposable graphical models, we...... construct a compact representation of the co-expression network that allows to identify the regions with high concentration of differentially expressed genes. It is argued that differentially expressed genes located in highly interconnected regions of the co-expression network are less informative than...

Regulation of eucaryotic gene expression

Energy Technology Data Exchange (ETDEWEB)

Brent, R.; Ptashne, M.S

1989-05-23

This patent describes a method of regulating the expression of a gene in a eucaryotic cell. The method consists of: providing in the eucaryotic cell, a peptide, derived from or substantially similar to a peptide of a procaryotic cell able to bind to DNA upstream from or within the gene, the amount of the peptide being sufficient to bind to the gene and thereby control expression of the gene.

Anterior cruciate ligament and meniscal injuries in sports: incidence, time of practice until injury, and limitations caused after trauma.

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Astur, Diego Costa; Xerez, Marcos; Rozas, João; Debieux, Pedro Vargas; Franciozi, Carlos Eduardo; Cohen, Moises

2016-01-01

To analyze the incidence of ACL and meniscal injuries in a population of recreational and elite athletes from Brazil and the relation of these injuries with their sports activities. This was a prospective observational study of 240 patients with ACL and/or meniscal injuries submitted to surgical treatment. Data of patients and sport modality, as well as Tegner score were registered in the first clinical evaluation. The patients were divided into three groups: (1) isolated rupture of the ACL; (2) ACL injury associated with meniscal injury; (3) isolated menisci injury. The majority of the patients belonged to group 1 (44.58%), followed by group 2 (30.2%) and 3 (25%). Most patients were soccer players. The mean time from sport practice to injury in group 1 was 17.81 years. In group 2, it was 17.3 years, and in group 3, 26.91 years. Soccer athletes presented ACL injury in 0.523/1000 h of practice and meniscal injury in 0.448/1000 h of practice. Before the injury, the mean Tegner score obtained for groups 1, 2, and 3 were 7.18, 7.34, and 6.53, respectively. After knee injury, those values were 3.07, 3.18, and 2.87, respectively. Soccer was the sport that caused the majority of lesions, regardless the group. Furthermore, patients from groups 1 and 2 had less time of practice prior to the injury (17.81 and 17.3 years) than the patients of group 3 (26.91 years). Women presented a higher risk to develop ACL and meniscal injuries in 1000 h of game/practice. Running, volleyball, and weightlifting are in ascending order of risk for ACL and/or meniscal injury. Regarding the return to sport practice, the efficiency of all athletes was impaired because of the injury.

Anterior cruciate ligament and meniscal injuries in sports: incidence, time of practice until injury, and limitations caused after trauma

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Diego Costa Astur

Full Text Available ABSTRACT OBJECTIVE: To analyze the incidence of ACL and meniscal injuries in a population of recreational and elite athletes from Brazil and the relation of these injuries with their sports activities. METHODS: This was a prospective observational study of 240 patients with ACL and/or meniscal injuries submitted to surgical treatment. Data of patients and sport modality, as well as Tegner score were registered in the first clinical evaluation. The patients were divided into three groups: (1 isolated rupture of the ACL; (2 ACL injury associated with meniscal injury; (3 isolated menisci injury. RESULTS: The majority of the patients belonged to group 1 (44.58%, followed by group 2 (30.2% and 3 (25%. Most patients were soccer players. The mean time from sport practice to injury in group 1 was 17.81 years. In group 2, it was 17.3 years, and in group 3, 26.91 years. Soccer athletes presented ACL injury in 0.523/1000 h of practice and meniscal injury in 0.448/1000 h of practice. Before the injury, the mean Tegner score obtained for groups 1, 2, and 3 were 7.18, 7.34, and 6.53, respectively. After knee injury, those values were 3.07, 3.18, and 2.87, respectively. CONCLUSION: Soccer was the sport that caused the majority of lesions, regardless the group. Furthermore, patients from groups 1 and 2 had less time of practice prior to the injury (17.81 and 17.3 years than the patients of group 3 (26.91 years. Women presented a higher risk to develop ACL and meniscal injuries in 1000 h of game/practice. Running, volleyball, and weightlifting are in ascending order of risk for ACL and/or meniscal injury. Regarding the return to sport practice, the efficiency of all athletes was impaired because of the injury.

Usefulness of meniscal width to transverse diameter ratio on coronal MRI in the diagnosis of incomplete discoid lateral meniscus

International Nuclear Information System (INIS)

Park, H.J.; Lee, S.Y.; Park, N.-H.; Chung, E.C.; Park, J.Y.; Kim, M.S.; Lee, E.J.

2014-01-01

Aim: To evaluate the clinical utility of the meniscal width to transverse diameter ratio (L/M ratio) of the lateral meniscus in the diagnosis of incomplete discoid lateral meniscus (IDLM) as compared with the arthroscopic diagnosis, meniscal width to tibial diameter ratio (L/T ratio) and conventional lateral meniscus width criteria. Materials and methods: This retrospective study sample included 41 patients with IDLM who underwent knee magnetic resonance imaging (MRI) and arthroscopy, as well as 50 controls with normal lateral menisci. MRI examinations were interpreted independently by two radiologists, both of whom were blinded to clinical information and radiological reports. Assessment of meniscal width (L), maximal transverse diameter of the lateral meniscus (M), and transverse diameter of the tibia (T) was carried out on central coronal sections that were observed to pass through the medial collateral ligament. L/M and L/T ratios were calculated. These results were correlated with arthroscopic findings and analysed statistically using categorical regression analysis and non-parametric correlation analysis. Using arthroscopic findings as the standard of reference, sensitivity and specificity were calculated for: (1) 12, 13, 14, and 15 mm meniscal width thresholds; (2) 40%, 50%, 60%, and 70% L/M ratio thresholds; and (3) 15%, 18%, 20%, and 25% L/T ratio thresholds. Results: The mean L/M ratio of the IDLM was approximately 67% and was statistically significantly higher than the control (44%). The best diagnostic discrimination was achieved using a threshold of 50%. The mean L/T ratio of the IDLM was approximately 23% and was statistically significant. The best diagnostic discrimination was achieved using a threshold of 18%. The threshold of 13 mm of meniscal width also showed high sensitivity and high specificity. Conclusion: The use of the L/M ratio or L/T ratio in combination with meniscal width criteria may be a useful method for evaluating IDLM

Identification, Characterization, and Utilization of Adult Meniscal Progenitor Cells

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2017-11-01

meniscal findings on knee MRI in middle-aged and elderly persons. N. Engl. J. Med. 359, 1108–1115.802 Stem Cell Reports j Vol. 3 j 789–803 j November 11...PBS, pH¼7.4) with protease inhibitors (Pierce Protease Inhibitor Tablets 88266, Thermo Fisher Scientific, Rockford, IL) at 4 1C for less than 24 h

Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden.

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Mattila, Ville M; Sihvonen, Raine; Paloneva, Juha; Felländer-Tsai, Li

2016-02-01

Knee arthroscopy is commonly performed to treat degenerative knee disease symptoms and traumatic meniscal tears. We evaluated whether the recent high-quality randomized control trials not favoring arthroscopic surgery for degenerative knee disease affected the procedure incidence and trends in Finland and Sweden. We conducted a bi-national registry-based study including all adult (aged ≥18 years) inpatient and outpatient arthroscopic surgeries performed for degenerative knee disease (osteoarthritis (OA) and degenerative meniscal tears) and traumatic meniscal tears in Finland between 1997 and 2012, and in Sweden between 2001 and 2012. In Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 10(5) person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 10(5) person-years in 1997 to 97 per 10(5) person-years in 2012, but not in Sweden. The incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries.

Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden

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Mattila, Ville M; Sihvonen, Raine; Paloneva, Juha; Felländer-Tsai, Li

2016-01-01

Background and purpose Knee arthroscopy is commonly performed to treat degenerative knee disease symptoms and traumatic meniscal tears. We evaluated whether the recent high-quality randomized control trials not favoring arthroscopic surgery for degenerative knee disease affected the procedure incidence and trends in Finland and Sweden. Patients and methods We conducted a bi-national registry-based study including all adult (aged ≥18 years) inpatient and outpatient arthroscopic surgeries performed for degenerative knee disease (osteoarthritis (OA) and degenerative meniscal tears) and traumatic meniscal tears in Finland between 1997 and 2012, and in Sweden between 2001 and 2012. Results In Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 105 person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 105 person-years in 1997 to 97 per 105 person-years in 2012, but not in Sweden. Interpretation The incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries. PMID:26122621

Value of Fat-Suppressed Proton-Density-Weighted Turbo Spin-Echo Sequences in Detecting Meniscal Lesions: Comparison with Arthroscopy

International Nuclear Information System (INIS)

Schaefer, F.K.W.; Schaefer, P.J.; Brossmann, J.; Frahm, C.; Hilgert, R.E.; Heller, M.; Jahnke, T.

2006-01-01

Purpose: To evaluate fat-suppressed (FS) proton-density-weighted (PDw) turbo spin-echo (TSE) magnetic resonance imaging (MRI) compared to arthroscopy in the detection of meniscal lesions. Material and Methods: In a prospective study, 31 knee joints were imaged on a 1.5T MR scanner before arthroscopy using the following sequences: (a) coronal and sagittal FS-PDw TSE (TR/TE: 4009/15 ms); (b) coronal T1w SE (TR/TE: 722/20 ms), and sagittal PDw TSE (TR/TE: 3800/15 ms). Other imaging parameters were: slice thickness 3 mm, FOV 160 mm, matrix 256x256. A total of 186 meniscal regions (62 menisci; anterior horn, body, posterior horn) were evaluated. Standard of reference was arthroscopy. Sensitivity, specificity, negative predictive value (npv), positive predictive value (ppv), and accuracy were calculated. Results: Arthroscopically, meniscal lesions were detected in 55/186 segments (35 medial and 20 lateral meniscal lesions). Sensitivity, specificity, npv, ppv, and accuracy for combination of coronal and sagittal FS PDw TSE were 91.4%, 98.3%, 95%, 97%, and 93.5% for the medial meniscus, and 90%, 98.6%, 97.3%, 94.7%, and 96.8% for the lateral. The results were comparable to the combination of coronal T1w SE and sagittal PDw TSE for the medial (88.6%, 98.3%, 93.4%, 96.9%, 91.4%) and the lateral (90%, 95.9%, 97.2%, 85.7%, 92.5%) meniscus. Conclusion: FS PDw TSE-MR sequences are an excellent alternative for the detection of meniscal lesions in comparison with diagnostic arthroscopy

Inferring gene expression dynamics via functional regression analysis

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Leng Xiaoyan

2008-01-01

Full Text Available Abstract Background Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene expression associated with different developmental stages to each other to study patterns of long-term developmental gene regulation. We use tools from functional data analysis to study dynamic changes by relating temporal gene expression profiles of different developmental stages to each other. Results We demonstrate that functional regression methodology can pinpoint relationships that exist between temporary gene expression profiles for different life cycle phases and incorporates dimension reduction as needed for these high-dimensional data. By applying these tools, gene expression profiles for pupa and adult phases are found to be strongly related to the profiles of the same genes obtained during the embryo phase. Moreover, one can distinguish between gene groups that exhibit relationships with positive and others with negative associations between later life and embryonal expression profiles. Specifically, we find a positive relationship in expression for muscle development related genes, and a negative relationship for strictly maternal genes for Drosophila, using temporal gene expression profiles. Conclusion Our findings point to specific reactivation patterns of gene expression during the Drosophila life cycle which differ in characteristic ways between various gene groups. Functional regression emerges as a useful tool for relating gene expression patterns from different developmental stages, and avoids the problems with large numbers of parameters and multiple testing that affect alternative approaches.

Synthetic promoter libraries- tuning of gene expression

DEFF Research Database (Denmark)

Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal

2006-01-01

knockout and strong overexpression. However, applications such as metabolic optimization and control analysis necessitate a continuous set of expression levels with only slight increments in strength to cover a specific window around the wildtype expression level of the studied gene; this requirement can......The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene...

Adaptive Evolution of Gene Expression in Drosophila.

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Nourmohammad, Armita; Rambeau, Joachim; Held, Torsten; Kovacova, Viera; Berg, Johannes; Lässig, Michael

2017-08-08

Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Adaptive Evolution of Gene Expression in Drosophila

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Armita Nourmohammad

2017-08-01

Full Text Available Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.

Patient-reported outcome measures for patients with meniscal tears: a systematic review of measurement properties and evaluation with the COSMIN checklist

Science.gov (United States)

Middleton, Robert; Beard, David J; Price, Andrew J; Hopewell, Sally

2017-01-01

Objective Meniscal tears occur frequently in the population and the most common surgical treatment, arthroscopic partial meniscectomy, is performed in approximately two million cases worldwide each year. The purpose of this systematic review is to summarise and critically appraise the evidence for the use of patient-reported outcome measures (PROMs) in patients with meniscal tears. Design A systematic review was undertaken. Data on reported measurement properties were extracted and the quality of the studies appraised according to Consensus-based Standards for the Selection of Health Measurement Instruments. Data sources A search of MEDLINE, Embase, AMED and PsycINFO, unlimited by language or publication date (last search 20 February 2017). Eligibility criteria for selecting studies Development and validation studies reporting the measurement properties of PROMs in patients with meniscal tears were included. Results 11 studies and 10 PROMs were included. The overall quality of studies was poor. For measurement of symptoms and functional status, there is only very limited evidence supporting the selection of either the Lysholm Knee Scale, International Knee Documentation Committee Subjective Knee Form or the Dutch version of the Knee injury and Osteoarthritis Outcome Score. For measuring health-related quality of life, only limited evidence supports the selection of the Western Ontario Meniscal Evaluation Tool (WOMET). Of all the PROMs evaluated, WOMET has the strongest evidence for content validity. Conclusion For patients with meniscal tears, there is poor quality and incomplete evidence regarding the validity of the currently available PROMs. Further research is required to ensure these PROMs truly reflect the symptoms, function and quality of life of patients with meniscal tears. PROSPERO registration number CRD42017056847. PMID:29030413

Identifying potential maternal genes of Bombyx mori using digital gene expression profiling

Science.gov (United States)

Xu, Pingzhen

2018-01-01

Maternal genes present in mature oocytes play a crucial role in the early development of silkworm. Although maternal genes have been widely studied in many other species, there has been limited research in Bombyx mori. High-throughput next generation sequencing provides a practical method for gene discovery on a genome-wide level. Herein, a transcriptome study was used to identify maternal-related genes from silkworm eggs. Unfertilized eggs from five different stages of early development were used to detect the changing situation of gene expression. The expressed genes showed different patterns over time. Seventy-six maternal genes were annotated according to homology analysis with Drosophila melanogaster. More than half of the differentially expressed maternal genes fell into four expression patterns, while the expression patterns showed a downward trend over time. The functional annotation of these material genes was mainly related to transcription factor activity, growth factor activity, nucleic acid binding, RNA binding, ATP binding, and ion binding. Additionally, twenty-two gene clusters including maternal genes were identified from 18 scaffolds. Altogether, we plotted a profile for the maternal genes of Bombyx mori using a digital gene expression profiling method. This will provide the basis for maternal-specific signature research and improve the understanding of the early development of silkworm. PMID:29462160

Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

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Boris P Hejblum

2015-06-01

Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

The rules of gene expression in plants: Organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana

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Gutiérrez Rodrigo A

2008-09-01

Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant

The functional landscape of mouse gene expression

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Zhang Wen

2004-12-01

Full Text Available Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

Expression of Sox genes in tooth development.

Science.gov (United States)

Kawasaki, Katsushige; Kawasaki, Maiko; Watanabe, Momoko; Idrus, Erik; Nagai, Takahiro; Oommen, Shelly; Maeda, Takeyasu; Hagiwara, Nobuko; Que, Jianwen; Sharpe, Paul T; Ohazama, Atsushi

2015-01-01

Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

Profiling Gene Expression in Germinating Brassica Roots.

Science.gov (United States)

Park, Myoung Ryoul; Wang, Yi-Hong; Hasenstein, Karl H

2014-01-01

Based on previously developed solid-phase gene extraction (SPGE) we examined the mRNA profile in primary roots of Brassica rapa seedlings for highly expressed genes like ACT7 (actin7), TUB (tubulin1), UBQ (ubiquitin), and low expressed GLK (glucokinase) during the first day post-germination. The assessment was based on the mRNA load of the SPGE probe of about 2.1 ng. The number of copies of the investigated genes changed spatially along the length of primary roots. The expression level of all genes differed significantly at each sample position. Among the examined genes ACT7 expression was most even along the root. UBQ was highest at the tip and root-shoot junction (RS). TUB and GLK showed a basipetal gradient. The temporal expression of UBQ was highest in the MZ 9 h after primary root emergence and higher than at any other sample position. Expressions of GLK in EZ and RS increased gradually over time. SPGE extraction is the result of oligo-dT and oligo-dA hybridization and the results illustrate that SPGE can be used for gene expression profiling at high spatial and temporal resolution. SPGE needles can be used within two weeks when stored at 4 °C. Our data indicate that gene expression studies that are based on the entire root miss important differences in gene expression that SPGE is able to resolve for example growth adjustments during gravitropism.

Unstable Expression of Commonly Used Reference Genes in Rat Pancreatic Islets Early after Isolation Affects Results of Gene Expression Studies.

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Lucie Kosinová

Full Text Available The use of RT-qPCR provides a powerful tool for gene expression studies; however, the proper interpretation of the obtained data is crucially dependent on accurate normalization based on stable reference genes. Recently, strong evidence has been shown indicating that the expression of many commonly used reference genes may vary significantly due to diverse experimental conditions. The isolation of pancreatic islets is a complicated procedure which creates severe mechanical and metabolic stress leading possibly to cellular damage and alteration of gene expression. Despite of this, freshly isolated islets frequently serve as a control in various gene expression and intervention studies. The aim of our study was to determine expression of 16 candidate reference genes and one gene of interest (F3 in isolated rat pancreatic islets during short-term cultivation in order to find a suitable endogenous control for gene expression studies. We compared the expression stability of the most commonly used reference genes and evaluated the reliability of relative and absolute quantification using RT-qPCR during 0-120 hrs after isolation. In freshly isolated islets, the expression of all tested genes was markedly depressed and it increased several times throughout the first 48 hrs of cultivation. We observed significant variability among samples at 0 and 24 hrs but substantial stabilization from 48 hrs onwards. During the first 48 hrs, relative quantification failed to reflect the real changes in respective mRNA concentrations while in the interval 48-120 hrs, the relative expression generally paralleled the results determined by absolute quantification. Thus, our data call into question the suitability of relative quantification for gene expression analysis in pancreatic islets during the first 48 hrs of cultivation, as the results may be significantly affected by unstable expression of reference genes. However, this method could provide reliable information

Evaluation of Meniscal Mechanics and Proteoglycan Content in a Modified Anterior Cruciate Ligament Transection Model

Science.gov (United States)

Fischenich, Kristine M.; Coatney, Garrett A.; Haverkamp, John H.; Button, Keith D.; DeCamp, Charlie; Haut, Roger C.; Haut Donahue, Tammy L.

2014-01-01

Post-traumatic osteoarthritis (PTOA) develops as a result of traumatic loading that causes tears of the soft tissues in the knee. A modified transection model, where the anterior cruciate ligament (ACL) and both menisci were transected, was used on skeletally mature Flemish Giant rabbits. Gross morphological assessments, elastic moduli, and glycosaminoglycan (GAG) coverage of the menisci were determined to quantify the amount of tissue damage 12 weeks post injury. This study is one of the first to monitor meniscal changes after inducing combined meniscal and ACL transections. A decrease in elastic moduli as well as a decrease in GAG coverage was seen. PMID:24749144

Comprehensive analysis of gene expression patterns of hedgehog-related genes

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Baillie David

2006-10-01

Full Text Available Abstract Background The Caenorhabditis elegans genome encodes ten proteins that share sequence similarity with the Hedgehog signaling molecule through their C-terminal autoprocessing Hint/Hog domain. These proteins contain novel N-terminal domains, and C. elegans encodes dozens of additional proteins containing only these N-terminal domains. These gene families are called warthog, groundhog, ground-like and quahog, collectively called hedgehog (hh-related genes. Previously, the expression pattern of seventeen genes was examined, which showed that they are primarily expressed in the ectoderm. Results With the completion of the C. elegans genome sequence in November 2002, we reexamined and identified 61 hh-related ORFs. Further, we identified 49 hh-related ORFs in C. briggsae. ORF analysis revealed that 30% of the genes still had errors in their predictions and we improved these predictions here. We performed a comprehensive expression analysis using GFP fusions of the putative intergenic regulatory sequence with one or two transgenic lines for most genes. The hh-related genes are expressed in one or a few of the following tissues: hypodermis, seam cells, excretory duct and pore cells, vulval epithelial cells, rectal epithelial cells, pharyngeal muscle or marginal cells, arcade cells, support cells of sensory organs, and neuronal cells. Using time-lapse recordings, we discovered that some hh-related genes are expressed in a cyclical fashion in phase with molting during larval development. We also generated several translational GFP fusions, but they did not show any subcellular localization. In addition, we also studied the expression patterns of two genes with similarity to Drosophila frizzled, T23D8.1 and F27E11.3A, and the ortholog of the Drosophila gene dally-like, gpn-1, which is a heparan sulfate proteoglycan. The two frizzled homologs are expressed in a few neurons in the head, and gpn-1 is expressed in the pharynx. Finally, we compare the

Development of a Micronized Meniscus Extracellular Matrix Scaffold for Potential Augmentation of Meniscal Repair and Regeneration.

Science.gov (United States)

Monibi, Farrah A; Bozynski, Chantelle C; Kuroki, Keiichi; Stoker, Aaron M; Pfeiffer, Ferris M; Sherman, Seth L; Cook, James L

2016-12-01

Decellularized scaffolds composed of extracellular matrix (ECM) hold promise for repair and regeneration of the meniscus, given the potential for ECM-based biomaterials to aid in stem cell recruitment, infiltration, and differentiation. The objectives of this study were to decellularize canine menisci to fabricate a micronized, ECM-derived scaffold and to determine the cytocompatibility and repair potential of the scaffold ex vivo. Menisci were decellularized with a combination of physical agitation and chemical treatments. For scaffold fabrication, decellularized menisci were cryoground into a powder and the size and morphology of the ECM particles were evaluated using scanning electron microscopy. Histologic and biochemical analyses of the scaffold confirmed effective decellularization with loss of proteoglycan from the tissue but no significant reduction in collagen content. When washed effectively, the decellularized scaffold was cytocompatible to meniscal fibrochondrocytes, synoviocytes, and whole meniscal tissue based on the resazurin reduction assay and histologic evaluation. In an ex vivo model for meniscal repair, radial tears were augmented with the scaffold delivered with platelet-rich plasma as a carrier, and compared to nonaugmented (standard-of-care) suture techniques. Histologically, there was no evidence of cellular migration or proliferation noted in any of the untreated or standard-of-care treatment groups after 40 days of culture. Conversely, cellular infiltration and proliferation were noted in scaffold-augmented repairs. These data suggest the potential for the scaffold to promote cellular survival, migration, and proliferation ex vivo. Further investigations are necessary to examine the potential for the scaffold to induce cellular differentiation and functional meniscal fibrochondrogenesis.

Simple Comparative Analyses of Differentially Expressed Gene Lists May Overestimate Gene Overlap.

Science.gov (United States)

Lawhorn, Chelsea M; Schomaker, Rachel; Rowell, Jonathan T; Rueppell, Olav

2018-04-16

Comparing the overlap between sets of differentially expressed genes (DEGs) within or between transcriptome studies is regularly used to infer similarities between biological processes. Significant overlap between two sets of DEGs is usually determined by a simple test. The number of potentially overlapping genes is compared to the number of genes that actually occur in both lists, treating every gene as equal. However, gene expression is controlled by transcription factors that bind to a variable number of transcription factor binding sites, leading to variation among genes in general variability of their expression. Neglecting this variability could therefore lead to inflated estimates of significant overlap between DEG lists. With computer simulations, we demonstrate that such biases arise from variation in the control of gene expression. Significant overlap commonly arises between two lists of DEGs that are randomly generated, assuming that the control of gene expression is variable among genes but consistent between corresponding experiments. More overlap is observed when transcription factors are specific to their binding sites and when the number of genes is considerably higher than the number of different transcription factors. In contrast, overlap between two DEG lists is always lower than expected when the genetic architecture of expression is independent between the two experiments. Thus, the current methods for determining significant overlap between DEGs are potentially confounding biologically meaningful overlap with overlap that arises due to variability in control of expression among genes, and more sophisticated approaches are needed.

Cell-Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath

Science.gov (United States)

2016-07-01

Engineering . Overlap: None Title: “Development of Novel Bioartificial Ligament Using Autologous Biological Scaffold and Cells” Grant#: W81XWH-13-2-0030...patient to rapid joint degeneration (i.e., osteoarthritis). Tissue engineering approaches, including the combination of cells, scaffolds, and...electrospun nano/microfibers comprising engineered scaffolds can mimic the ultrastructure of the native meniscal extracellular matrix (ECM); when seeded with

Methods for monitoring multiple gene expression

Energy Technology Data Exchange (ETDEWEB)

Berka, Randy [Davis, CA; Bachkirova, Elena [Davis, CA; Rey, Michael [Davis, CA

2012-05-01

The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

Methods for monitoring multiple gene expression

Energy Technology Data Exchange (ETDEWEB)

Berka, Randy; Bachkirova, Elena; Rey, Michael

2013-10-01

The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

Determinants of human adipose tissue gene expression

DEFF Research Database (Denmark)

Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

2012-01-01

weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong...... interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index...... on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently...

LINE FUSION GENES: a database of LINE expression in human genes

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Park Hong-Seog

2006-06-01

Full Text Available Abstract Background Long Interspersed Nuclear Elements (LINEs are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. Description We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. Conclusion We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. Availability http://www.primate.or.kr/line

Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko

2015-12-23

Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

Social Regulation of Gene Expression in Threespine Sticklebacks.

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Anna K Greenwood

Full Text Available Identifying genes that are differentially expressed in response to social interactions is informative for understanding the molecular basis of social behavior. To address this question, we described changes in gene expression as a result of differences in the extent of social interactions. We housed threespine stickleback (Gasterosteus aculeatus females in either group conditions or individually for one week, then measured levels of gene expression in three brain regions using RNA-sequencing. We found that numerous genes in the hindbrain/cerebellum had altered expression in response to group or individual housing. However, relatively few genes were differentially expressed in either the diencephalon or telencephalon. The list of genes upregulated in fish from social groups included many genes related to neural development and cell adhesion as well as genes with functions in sensory signaling, stress, and social and reproductive behavior. The list of genes expressed at higher levels in individually-housed fish included several genes previously identified as regulated by social interactions in other animals. The identified genes are interesting targets for future research on the molecular mechanisms of normal social interactions.

A constructive approach to gene expression dynamics

International Nuclear Information System (INIS)

Ochiai, T.; Nacher, J.C.; Akutsu, T.

2004-01-01

Recently, experiments on mRNA abundance (gene expression) have revealed that gene expression shows a stationary organization described by a scale-free distribution. Here we propose a constructive approach to gene expression dynamics which restores the scale-free exponent and describes the intermediate state dynamics. This approach requires only one assumption: Markov property

Stably Expressed Genes Involved in Basic Cellular Functions.

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Kejian Wang

Full Text Available Stably Expressed Genes (SEGs whose expression varies within a narrow range may be involved in core cellular processes necessary for basic functions. To identify such genes, we re-analyzed existing RNA-Seq gene expression profiles across 11 organs at 4 developmental stages (from immature to old age in both sexes of F344 rats (n = 4/group; 320 samples. Expression changes (calculated as the maximum expression / minimum expression for each gene of >19000 genes across organs, ages, and sexes ranged from 2.35 to >109-fold, with a median of 165-fold. The expression of 278 SEGs was found to vary ≤4-fold and these genes were significantly involved in protein catabolism (proteasome and ubiquitination, RNA transport, protein processing, and the spliceosome. Such stability of expression was further validated in human samples where the expression variability of the homologous human SEGs was significantly lower than that of other genes in the human genome. It was also found that the homologous human SEGs were generally less subject to non-synonymous mutation than other genes, as would be expected of stably expressed genes. We also found that knockout of SEG homologs in mouse models was more likely to cause complete preweaning lethality than non-SEG homologs, corroborating the fundamental roles played by SEGs in biological development. Such stably expressed genes and pathways across life-stages suggest that tight control of these processes is important in basic cellular functions and that perturbation by endogenous (e.g., genetics or exogenous agents (e.g., drugs, environmental factors may cause serious adverse effects.

Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

NARCIS (Netherlands)

Peters, Dorien J.M.; Lookeren Campagne, Michiel M. van; Haastert, Peter J.M. van; Spek, Wouter; Schaap, Pauline

1989-01-01

We investigated the effect of Li+ on two types of cyclic AMP-regulated gene expression and on basal and cyclic AMP-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Li+ effectively inhibits cyclic AMP-induced prespore gene expression, half-maximal inhibition occurring at about 2mM-LiCl.

Validation of commonly used reference genes for sleep-related gene expression studies

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Castro Rosa MRPS

2009-05-01

Full Text Available Abstract Background Sleep is a restorative process and is essential for maintenance of mental and physical health. In an attempt to understand the complexity of sleep, multidisciplinary strategies, including genetic approaches, have been applied to sleep research. Although quantitative real time PCR has been used in previous sleep-related gene expression studies, proper validation of reference genes is currently lacking. Thus, we examined the effect of total or paradoxical sleep deprivation (TSD or PSD on the expression stability of the following frequently used reference genes in brain and blood: beta-actin (b-actin, beta-2-microglobulin (B2M, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, and hypoxanthine guanine phosphoribosyl transferase (HPRT. Results Neither TSD nor PSD affected the expression stability of all tested genes in both tissues indicating that b-actin, B2M, GAPDH and HPRT are appropriate reference genes for the sleep-related gene expression studies. In order to further verify these results, the relative expression of brain derived neurotrophic factor (BDNF and glycerol-3-phosphate dehydrogenase1 (GPD1 was evaluated in brain and blood, respectively. The normalization with each of four reference genes produced similar pattern of expression in control and sleep deprived rats, but subtle differences in the magnitude of expression fold change were observed which might affect the statistical significance. Conclusion This study demonstrated that sleep deprivation does not alter the expression stability of commonly used reference genes in brain and blood. Nonetheless, the use of multiple reference genes in quantitative RT-PCR is required for the accurate results.

Risk factors, diagnosis and non-surgical treatment for meniscal tears: evidence and recommendations: a statement paper commissioned by the Danish Society of Sports Physical Therapy (DSSF).

Science.gov (United States)

Thorlund, Jonas Bloch; Juhl, Carsten Bogh; Ingelsrud, Lina Holm; Skou, Søren Thorgaard

2018-05-01

This statement aimed at summarising and appraising the available evidence for risk factors, diagnostic tools and non-surgical treatments for patients with meniscal tears. We systematically searched electronic databases using a pragmatic search strategy approach. Included studies were synthesised quantitatively or qualitatively, as appropriate. Strength of evidence was determined according to the Grading of Recommendations Assessment Development and Evaluation framework. Low-quality evidence suggested that overweight (degenerative tears, k=3), male sex (k=4), contact and pivoting sports (k=2), and frequent occupational kneeling/squatting (k=3) were risk factors for meniscal tears. There was low to moderate quality evidence for low to high positive and negative predictive values, depending on the underlying prevalence of meniscal tears for four common diagnostic tests (k=15, n=2474). Seven trials investigated exercise versus surgery (k=2) or the effect of surgery in addition to exercise (k=5) for degenerative meniscal tears. There was moderate level of evidence for exercise improving self-reported pain (Effect Size (ES)-0.51, 95% CI -1.16 to 0.13) and function (ES -0.06, 95% CI -0.23 to 0.11) to the same extent as surgery, and improving muscle strength to a greater extent than surgery (ES -0.45, 95% CI -0.62 to -0.29). High-quality evidence showed no clinically relevant effect of surgery in addition to exercise on pain (ES 0.18, 95% 0.05 to 0.32) and function (ES, 0.13 95% CI -0.03 to 0.28) for patients with degenerative meniscal tears. No randomised trials comparing non-surgical treatments with surgery in patients younger than 40 years of age or patients with traumatic meniscal tears were identified. Diagnosis of meniscal tears is challenging as all clinical diagnostic tests have high risk of misclassification. Exercise therapy should be recommended as the treatment of choice for middle-aged and older patients with degenerative meniscal lesions. Evidence on

Stochastic gene expression in Arabidopsis thaliana.

Science.gov (United States)

Araújo, Ilka Schultheiß; Pietsch, Jessica Magdalena; Keizer, Emma Mathilde; Greese, Bettina; Balkunde, Rachappa; Fleck, Christian; Hülskamp, Martin

2017-12-14

Although plant development is highly reproducible, some stochasticity exists. This developmental stochasticity may be caused by noisy gene expression. Here we analyze the fluctuation of protein expression in Arabidopsis thaliana. Using the photoconvertible KikGR marker, we show that the protein expressions of individual cells fluctuate over time. A dual reporter system was used to study extrinsic and intrinsic noise of marker gene expression. We report that extrinsic noise is higher than intrinsic noise and that extrinsic noise in stomata is clearly lower in comparison to several other tissues/cell types. Finally, we show that cells are coupled with respect to stochastic protein expression in young leaves, hypocotyls and roots but not in mature leaves. Our data indicate that stochasticity of gene expression can vary between tissues/cell types and that it can be coupled in a non-cell-autonomous manner.

Deriving Trading Rules Using Gene Expression Programming

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Adrian VISOIU

2011-01-01

Full Text Available This paper presents how buy and sell trading rules are generated using gene expression programming with special setup. Market concepts are presented and market analysis is discussed with emphasis on technical analysis and quantitative methods. The use of genetic algorithms in deriving trading rules is presented. Gene expression programming is applied in a form where multiple types of operators and operands are used. This gives birth to multiple gene contexts and references between genes in order to keep the linear structure of the gene expression programming chromosome. The setup of multiple gene contexts is presented. The case study shows how to use the proposed gene setup to derive trading rules encoded by Boolean expressions, using a dataset with the reference exchange rates between the Euro and the Romanian leu. The conclusions highlight the positive results obtained in deriving useful trading rules.

Using PCR to Target Misconceptions about Gene Expression

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Leslie K. Wright

2013-02-01

Full Text Available We present a PCR-based laboratory exercise that can be used with first- or second-year biology students to help overcome common misconceptions about gene expression. Biology students typically do not have a clear understanding of the difference between genes (DNA and gene expression (mRNA/protein and often believe that genes exist in an organism or cell only when they are expressed. This laboratory exercise allows students to carry out a PCR-based experiment designed to challenge their misunderstanding of the difference between genes and gene expression. Students first transform E. coli with an inducible GFP gene containing plasmid and observe induced and un-induced colonies. The following exercise creates cognitive dissonance when actual PCR results contradict their initial (incorrect predictions of the presence of the GFP gene in transformed cells. Field testing of this laboratory exercise resulted in learning gains on both knowledge and application questions on concepts related to genes and gene expression.

Differential gene expression during Trypanosoma cruzi metacyclogenesis

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Marco Aurelio Krieger

1999-09-01

Full Text Available The transformation of epimastigotes into metacyclic trypomastigotes involves changes in the pattern of expressed genes, resulting in important morphological and functional differences between these developmental forms of Trypanosoma cruzi. In order to identify and characterize genes involved in triggering the metacyclogenesis process and in conferring to metacyclic trypomastigotes their stage specific biological properties, we have developed a method allowing the isolation of genes specifically expressed when comparing two close related cell populations (representation of differential expression or RDE. The method is based on the PCR amplification of gene sequences selected by hybridizing and subtracting the populations in such a way that after some cycles of hybridization-amplification genes specific to a given population are highly enriched. The use of this method in the analysis of differential gene expression during T. cruzi metacyclogenesis (6 hr and 24 hr of differentiation and metacyclic trypomastigotes resulted in the isolation of several clones from each time point. Northern blot analysis showed that some genes are transiently expressed (6 hr and 24 hr differentiating cells, while others are present in differentiating cells and in metacyclic trypomastigotes. Nucleotide sequencing of six clones characterized so far showed that they do not display any homology to gene sequences available in the GeneBank.

Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon

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Hackett Perry B

2006-06-01

Full Text Available Abstract Background Insertional mutagenesis techniques with transposable elements have been popular among geneticists studying model organisms from E. coli to Drosophila and, more recently, the mouse. One such element is the Sleeping Beauty (SB transposon that has been shown in several studies to be an effective insertional mutagen in the mouse germline. SB transposon vector studies have employed different functional elements and reporter molecules to disrupt and report the expression of endogenous mouse genes. We sought to generate a transposon system that would be capable of reporting the expression pattern of a mouse gene while allowing for conditional expression of a gene of interest in a tissue- or temporal-specific pattern. Results Here we report the systematic development and testing of a transposon-based gene-trap system incorporating the doxycycline-repressible Tet-Off (tTA system that is capable of activating the expression of genes under control of a Tet response element (TRE promoter. We demonstrate that the gene trap system is fully functional in vitro by introducing the "gene-trap tTA" vector into human cells by transposition and identifying clones that activate expression of a TRE-luciferase transgene in a doxycycline-dependent manner. In transgenic mice, we mobilize gene-trap tTA vectors, discover parameters that can affect germline mobilization rates, and identify candidate gene insertions to demonstrate the in vivo functionality of the vector system. We further demonstrate that the gene-trap can act as a reporter of endogenous gene expression and it can be coupled with bioluminescent imaging to identify genes with tissue-specific expression patterns. Conclusion Akin to the GAL4/UAS system used in the fly, we have made progress developing a tool for mutating and revealing the expression of mouse genes by generating the tTA transactivator in the presence of a secondary TRE-regulated reporter molecule. A vector like the gene

Analysis of multiplex gene expression maps obtained by voxelation

Directory of Open Access Journals (Sweden)

Smith Desmond J

2009-04-01

Full Text Available Abstract Background Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological disease. Researchers have previously used voxelation in combination with microarrays for acquisition of genome-wide atlases of expression patterns in the mouse brain. On the other hand, some work has been performed on studying gene functions, without taking into account the location information of a gene's expression in a mouse brain. In this paper, we present an approach for identifying the relation between gene expression maps obtained by voxelation and gene functions. Results To analyze the dataset, we chose typical genes as queries and aimed at discovering similar gene groups. Gene similarity was determined by using the wavelet features extracted from the left and right hemispheres averaged gene expression maps, and by the Euclidean distance between each pair of feature vectors. We also performed a multiple clustering approach on the gene expression maps, combined with hierarchical clustering. Among each group of similar genes and clusters, the gene function similarity was measured by calculating the average gene function distances in the gene ontology structure. By applying our methodology to find similar genes to certain target genes we were able to improve our understanding of gene expression patterns and gene functions. By applying the clustering analysis method, we obtained significant clusters, which have both very similar gene expression maps and very similar gene functions respectively to their corresponding gene ontologies. The cellular component ontology resulted in prominent clusters expressed in cortex and corpus callosum. The molecular function ontology gave prominent clusters in cortex, corpus callosum and hypothalamus. The biological process ontology resulted in clusters in cortex, hypothalamus and choroid plexus. Clusters from all three ontologies combined were most prominently expressed in

Analysis of multiplex gene expression maps obtained by voxelation.

Science.gov (United States)

An, Li; Xie, Hongbo; Chin, Mark H; Obradovic, Zoran; Smith, Desmond J; Megalooikonomou, Vasileios

2009-04-29

Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological disease. Researchers have previously used voxelation in combination with microarrays for acquisition of genome-wide atlases of expression patterns in the mouse brain. On the other hand, some work has been performed on studying gene functions, without taking into account the location information of a gene's expression in a mouse brain. In this paper, we present an approach for identifying the relation between gene expression maps obtained by voxelation and gene functions. To analyze the dataset, we chose typical genes as queries and aimed at discovering similar gene groups. Gene similarity was determined by using the wavelet features extracted from the left and right hemispheres averaged gene expression maps, and by the Euclidean distance between each pair of feature vectors. We also performed a multiple clustering approach on the gene expression maps, combined with hierarchical clustering. Among each group of similar genes and clusters, the gene function similarity was measured by calculating the average gene function distances in the gene ontology structure. By applying our methodology to find similar genes to certain target genes we were able to improve our understanding of gene expression patterns and gene functions. By applying the clustering analysis method, we obtained significant clusters, which have both very similar gene expression maps and very similar gene functions respectively to their corresponding gene ontologies. The cellular component ontology resulted in prominent clusters expressed in cortex and corpus callosum. The molecular function ontology gave prominent clusters in cortex, corpus callosum and hypothalamus. The biological process ontology resulted in clusters in cortex, hypothalamus and choroid plexus. Clusters from all three ontologies combined were most prominently expressed in cortex and corpus callosum. The experimental

A comparative gene expression database for invertebrates

Directory of Open Access Journals (Sweden)

Ormestad Mattias

2011-08-01

Full Text Available Abstract Background As whole genome and transcriptome sequencing gets cheaper and faster, a great number of 'exotic' animal models are emerging, rapidly adding valuable data to the ever-expanding Evo-Devo field. All these new organisms serve as a fantastic resource for the research community, but the sheer amount of data, some published, some not, makes detailed comparison of gene expression patterns very difficult to summarize - a problem sometimes even noticeable within a single lab. The need to merge existing data with new information in an organized manner that is publicly available to the research community is now more necessary than ever. Description In order to offer a homogenous way of storing and handling gene expression patterns from a variety of organisms, we have developed the first web-based comparative gene expression database for invertebrates that allows species-specific as well as cross-species gene expression comparisons. The database can be queried by gene name, developmental stage and/or expression domains. Conclusions This database provides a unique tool for the Evo-Devo research community that allows the retrieval, analysis and comparison of gene expression patterns within or among species. In addition, this database enables a quick identification of putative syn-expression groups that can be used to initiate, among other things, gene regulatory network (GRN projects.

Genetic Variants Contribute to Gene Expression Variability in Humans

Science.gov (United States)

Hulse, Amanda M.; Cai, James J.

2013-01-01

Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

Correction of gene expression data

DEFF Research Database (Denmark)

Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

2014-01-01

This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

Gene expression in colorectal cancer

DEFF Research Database (Denmark)

Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

2002-01-01

Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

Multiscale Embedded Gene Co-expression Network Analysis.

Directory of Open Access Journals (Sweden)

Won-Min Song

2015-11-01

Full Text Available Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3, the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA by: i introducing quality control of co-expression similarities, ii parallelizing embedded network construction, and iii developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs. We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA. MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

Multiscale Embedded Gene Co-expression Network Analysis.

Science.gov (United States)

Song, Won-Min; Zhang, Bin

2015-11-01

Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

Evaluation of changes in vertical ground reaction forces as indicators of meniscal damage after transection of the cranial cruciate ligament in dogs.

Science.gov (United States)

Trumble, Troy N; Billinghurst, R Clark; Bendele, Alison M; McIlwraith, C Wayne

2005-01-01

To determine whether decreases in peak vertical force of the hind limb after transection of the cranial cruciate ligament (CrCL) would be indicative of medial meniscal damage in dogs. 39 purpose-bred adult male Walker Hounds. The right CrCL was transected arthroscopically. Force plate measurements of the right hind limb were made prior to and 2, 4, 10, and 18 weeks after transection of the CrCL. Only dogs with > or =10% decreases in peak vertical force after week 2 were considered to have potential meniscal damage. Dogs that did not have > or =10% decreases in peak vertical force at any time point after week 2 were assigned to group 1. Group 2 dogs had > or =10% decreases in peak vertical force from weeks 2 to 4 only. Group 3 and 4 dogs had > or =10% decreases in peak vertical force from weeks 4 to 10 only or from weeks 10 to 18 only, respectively. Damage to menisci and articular cartilage was graded at week 18, and grades for groups 2 to 4 were compared with those of group 1. The percentage change in peak vertical force and impulse area was significantly different in groups 2 (n = 4), 3 (4), and 4 (4) at the end of each measurement period (weeks 4, 10, and 18, respectively) than in group 1 (27). The meniscal grade for groups 2 to 4 was significantly higher than for group 1. A > or =10% decrease in peak vertical force had sensitivity of 52% and accuracy of 72% for identifying dogs with moderate to severe medial meniscal damage. In dogs with transected or ruptured CrCLs, force plate analysis can detect acute exacerbation of lameness, which may be the result of secondary meniscal damage, and provide an objective noninvasive technique that delineates the temporal pattern of medial meniscal injury.

Meniscal replacement using a porous polymer prosthesis : A preliminary study in the dog

NARCIS (Netherlands)

Veth, RPH; Jansen, HWB; Nielsen, HKL; deGroot, JH; Pennings, AJ

A porous polyurethane prosthesis was used to replace the lateral meniscus in the dog. After an initial ingrowth of fibrous tissue, the prostheses became filled with tissue strongly resembling normal meniscal fibrocartilage. Although less severe than seen after total meniscectomy, cartilage

Vascular Gene Expression: A Hypothesis

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Angélica Concepción eMartínez-Navarro

2013-07-01

Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

GSEH: A Novel Approach to Select Prostate Cancer-Associated Genes Using Gene Expression Heterogeneity.

Science.gov (United States)

Kim, Hyunjin; Choi, Sang-Min; Park, Sanghyun

2018-01-01

When a gene shows varying levels of expression among normal people but similar levels in disease patients or shows similar levels of expression among normal people but different levels in disease patients, we can assume that the gene is associated with the disease. By utilizing this gene expression heterogeneity, we can obtain additional information that abets discovery of disease-associated genes. In this study, we used collaborative filtering to calculate the degree of gene expression heterogeneity between classes and then scored the genes on the basis of the degree of gene expression heterogeneity to find "differentially predicted" genes. Through the proposed method, we discovered more prostate cancer-associated genes than 10 comparable methods. The genes prioritized by the proposed method are potentially significant to biological processes of a disease and can provide insight into them.

The evolution of gene expression in primates

OpenAIRE

Tashakkori Ghanbarian, Avazeh

2015-01-01

The evolution of a gene’s expression profile is commonly assumed to be independent of its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between expression of neighboring genes in extant taxa. Indeed, in all eukaryotic genomes, genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their e...

Development of a Chinese version of the Western Ontario Meniscal Evaluation Tool: cross-cultural adaptation and psychometric evaluation.

Science.gov (United States)

Tong, W W; Wang, W; Xu, W D

2016-08-15

The Western Ontario Meniscal Evaluation Tool (WOMET) is a questionnaire designed to evaluate the health-related quality of life (HRQOL) of patients with meniscal pathology. Our study aims to culturally adapt and validate the WOMET into a Chinese version. We translated the WOMET into Chinese. Then, a total of 121 patients with meniscal pathology were invited to participate in this study. To assess the test-retest reliability, the Chinese version WOMET was completed twice at 7-day intervals by the participants. The construct validity was assessed using Pearson's correlation coefficient or Spearman's correlation to test for correlations among the Chinese version WOMET and the eight domains of Short Form-36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the International Knee Documentation Committee (IKDC) score. Responsiveness was tested by comparison of the preoperative and postoperative scores of the Chinese version WOMET. The test-retest reliability of the overall scale and different domains were all found to be excellent. The Cronbach's α was 0.90. The Chinese version WOMET correlated well with other questionnaires which suggested good construct validity. We observed no ceiling and floor effects of the Chinese version WOMET. We also found good responsiveness for the effect size, and the standardized response mean values were 0.86 and 1.11. The Chinese version of the WOMET appears to be reliable and valid in evaluating patients with meniscal pathology.

Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

International Nuclear Information System (INIS)

Salem, Tamer Z.; Zhang, Fengrui; Thiem, Suzanne M.

2013-01-01

Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

Energy Technology Data Exchange (ETDEWEB)

Salem, Tamer Z. [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbial Molecular Biology, AGERI, Agricultural Research Center, Giza 12619 (Egypt); Division of Biomedical Sciences, Zewail University, Zewail City of Science and Technology, Giza 12588 (Egypt); Zhang, Fengrui [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Thiem, Suzanne M., E-mail: smthiem@msu.edu [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

2013-01-20

Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

Meniscal tissue regeneration in porous 50/50 copoly(L-lactide/epsilon-caprolactone) implants

NARCIS (Netherlands)

de Groot, J. H.; Zijlstra, F. M.; Kuipers, HW; Pennings, A. J.; Veth, RPH; Jansen, HWB

Porous materials of a high-molecular-weight 50/50 copolymer of L-lactide and epsilon-caprolactone with different compression moduli were used for meniscal repair. In contrast to the previously used 4,4'-diphenylmethane and 1,6-trans-cyclohexane diisocyanates containing polyurethanes, degradation

Treatment of Painful, Irreparable Partial Meniscal Defects With a Polyurethane Scaffold: Midterm Clinical Outcomes and Survival Analysis.

Science.gov (United States)

Dhollander, Aad; Verdonk, Peter; Verdonk, René

2016-10-01

A biodegradable polyurethane scaffold was designed to fulfill a challenging clinical need in the treatment of patients with painful, irreparable partial meniscal defects. The use of an acellular polyurethane scaffold for new tissue generation in irreparable, partial meniscal defects provides both midterm pain relief and improved functionality. Case series; Level of evidence, 4. A total of 44 patients with irreparable, partial meniscal defects (29 medial and 15 lateral) were implanted with a polyurethane scaffold in a prospective, single-arm proof-of-principle study with a minimum 5-year follow-up. Clinical outcomes were measured with the visual analog scale (VAS) for pain, International Knee Documentation Committee (IKDC), and Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline and at 2- and 5-year follow-up. Magnetic resonance imaging (MRI) was used to evaluate the meniscal implant and cartilage status of the index compartment. Kaplan-Meier time-to-treatment failure distributions were also performed. Removal of the scaffold, conversion to a meniscal transplant, or unicompartmental/total knee arthroplasty was used as endpoints. Seven patients were lost to follow-up (15.9%). The patients who participated in this study showed significant clinical improvement after surgery (mean [±SD] at baseline, 2 years, and 5 years: 56.2 ± 21.6, 24.6 ± 22.7, and 19.3 ± 26.9, respectively [VAS]; 206.5 ± 79.7, 329.8 ± 108.9, and 333.6 ± 112.2, respectively [total KOOS]). MRI of the scaffolds showed a smaller sized implant when compared with the native meniscus with an irregular surface at 2- and 5-year follow-up. A stable cartilage status of the index compartment at 5-year follow-up was demonstrated in 46.7% of patients compared with the baseline status. During the follow-up period, 62.2% of the implants survived. At final follow-up, 66.7% of the medial scaffolds were still functioning versus 53.8% of the lateral scaffolds. A polyurethane meniscal implant can

Widespread ectopic expression of olfactory receptor genes

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Yanai Itai

2006-05-01

Full Text Available Abstract Background Olfactory receptors (ORs are the largest gene family in the human genome. Although they are expected to be expressed specifically in olfactory tissues, some ectopic expression has been reported, with special emphasis on sperm and testis. The present study systematically explores the expression patterns of OR genes in a large number of tissues and assesses the potential functional implication of such ectopic expression. Results We analyzed the expression of hundreds of human and mouse OR transcripts, via EST and microarray data, in several dozens of human and mouse tissues. Different tissues had specific, relatively small OR gene subsets which had particularly high expression levels. In testis, average expression was not particularly high, and very few highly expressed genes were found, none corresponding to ORs previously implicated in sperm chemotaxis. Higher expression levels were more common for genes with a non-OR genomic neighbor. Importantly, no correlation in expression levels was detected for human-mouse orthologous pairs. Also, no significant difference in expression levels was seen between intact and pseudogenized ORs, except for the pseudogenes of subfamily 7E which has undergone a human-specific expansion. Conclusion The OR superfamily as a whole, show widespread, locus-dependent and heterogeneous expression, in agreement with a neutral or near neutral evolutionary model for transcription control. These results cannot reject the possibility that small OR subsets might play functional roles in different tissues, however considerable care should be exerted when offering a functional interpretation for ectopic OR expression based only on transcription information.

Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

Science.gov (United States)

Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

2013-01-01

The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

Knee function and knee muscle strength in middle-aged patients with degenerative meniscal tears eligible for arthroscopic partial meniscectomy

DEFF Research Database (Denmark)

Stensrud, Silje; Risberg, May Arna; Roos, Ewa M.

2014-01-01

BACKGROUND: Functional limitations exist postmeniscectomy, but preoperative data are scarce. PURPOSE: To examine knee function, knee muscle strength and performance in middle-aged patients with degenerative meniscal tears, eligible for arthroscopic partial meniscectomy. STUDY DESIGN: Cross......-sectional study. METHODS: Eighty-two participants with MRI verified degenerative meniscal tear (35% women, mean age 49 years) answered the Knee injury and Osteoarthritis Outcome Score (KOOS) and were tested for isokinetic knee muscle strength and lower extremity performance (one-leg hop for distance, 6 m timed...

Dynamic association rules for gene expression data analysis.

Science.gov (United States)

Chen, Shu-Chuan; Tsai, Tsung-Hsien; Chung, Cheng-Han; Li, Wen-Hsiung

2015-10-14

The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed

Gene expression in periodontal tissues following treatment

Directory of Open Access Journals (Sweden)

Eisenacher Martin

2008-07-01

Full Text Available Abstract Background In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of immune and inflammatory genes in periodontal tissues from sites with severe chronic periodontitis following periodontal therapy in order to identify genes involved in tissue homeostasis. Gingival biopsies from 12 patients with severe chronic periodontitis were taken six to eight weeks following non-surgical periodontal therapy, and from 11 healthy controls. As internal standard, RNA of an immortalized human keratinocyte line (HaCaT was used. Total RNA was subjected to gene expression profiling using a commercially available microarray system focusing on inflammation-related genes. Post-hoc confirmation of selected genes was done by Realtime-PCR. Results Out of the 136 genes analyzed, the 5% most strongly expressed genes compared to healthy controls were Interleukin-12A (IL-12A, Versican (CSPG-2, Matrixmetalloproteinase-1 (MMP-1, Down syndrome critical region protein-1 (DSCR-1, Macrophage inflammatory protein-2β (Cxcl-3, Inhibitor of apoptosis protein-1 (BIRC-1, Cluster of differentiation antigen 38 (CD38, Regulator of G-protein signalling-1 (RGS-1, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene (C-FOS; the 5% least strongly expressed genes were Receptor-interacting Serine/Threonine Kinase-2 (RIP-2, Complement component 3 (C3, Prostaglandin-endoperoxide synthase-2 (COX-2, Interleukin-8 (IL-8, Endothelin-1 (EDN-1, Plasminogen activator inhibitor type-2 (PAI-2, Matrix-metalloproteinase-14 (MMP-14, and Interferon regulating factor-7 (IRF-7. Conclusion Gene expression profiles found in periodontal tissues following

Gene expression profiles in skeletal muscle after gene electrotransfer

DEFF Research Database (Denmark)

Hojman, Pernille; Zibert, John R; Gissel, Hanne

2007-01-01

BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

Comparative gene expression between two yeast species

Directory of Open Access Journals (Sweden)

Guan Yuanfang

2013-01-01

Full Text Available Abstract Background Comparative genomics brings insight into sequence evolution, but even more may be learned by coupling sequence analyses with experimental tests of gene function and regulation. However, the reliability of such comparisons is often limited by biased sampling of expression conditions and incomplete knowledge of gene functions across species. To address these challenges, we previously systematically generated expression profiles in Saccharomyces bayanus to maximize functional coverage as compared to an existing Saccharomyces cerevisiae data repository. Results In this paper, we take advantage of these two data repositories to compare patterns of ortholog expression in a wide variety of conditions. First, we developed a scalable metric for expression divergence that enabled us to detect a significant correlation between sequence and expression conservation on the global level, which previous smaller-scale expression studies failed to detect. Despite this global conservation trend, between-species gene expression neighborhoods were less well-conserved than within-species comparisons across different environmental perturbations, and approximately 4% of orthologs exhibited a significant change in co-expression partners. Furthermore, our analysis of matched perturbations collected in both species (such as diauxic shift and cell cycle synchrony demonstrated that approximately a quarter of orthologs exhibit condition-specific expression pattern differences. Conclusions Taken together, these analyses provide a global view of gene expression patterns between two species, both in terms of the conditions and timing of a gene's expression as well as co-expression partners. Our results provide testable hypotheses that will direct future experiments to determine how these changes may be specified in the genome.

Interactive visualization of gene regulatory networks with associated gene expression time series data

NARCIS (Netherlands)

Westenberg, M.A.; Hijum, van S.A.F.T.; Lulko, A.T.; Kuipers, O.P.; Roerdink, J.B.T.M.; Linsen, L.; Hagen, H.; Hamann, B.

2008-01-01

We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

Kissing contusion between the posterolateral tibial plateau and lateral femoral condyle: associated ligament and meniscal tears

International Nuclear Information System (INIS)

Hong, Hyun Pyo; Lee, Jae Gue; Park, Ji Seon; Ryu, Kyung Nam

2004-01-01

Kissing contusion between the posterolateral tibial plateau and lateral femoral condyle is frequently found in association with a tear of the anterior cruciate liagment (ACL). The purpose of this study was to determine which ligamentous and meniscal tears are associated with kissing contusion. We retrospectively reviewed the findings depicted by 323 consecutive MR images of the knee and confirmed at arthroscopy. For the diagnosis of disruption, ligaments, medial menisci (MM) and lateral menisci (LM) were evaluated using accepted criteria. We compared the prevalence and location of meniscal and ligamentous tears between group I (44 knees with kissing contusion) and group II (279 knees without kissing contusion). For statistical analysis the chi-square test was used. ACLs were torn in all 44 knees (100%) with kissing contusion, and 78 (28%) of 279 without kissing contusion. There were ten medial collateral ligament (MCL) tears (23%) in group I, and 17 MCL tears (6%), five lateral collateral ligament (LCL) tears (2%) and ten posterior cruciate ligament (PCL) tears (4%) in group II. In group I, meniscal tears were found in 22 MM (50%) and in 19 LM (43%), while in group II, they occurred in 128 MM (46%) and 128 LM (46%), In group I, 17 (77%) of 22 MM tears and 13 (68%) of 19 LM tears were located in the posterior horn, while in group II, the corresponding figures were 97/128 (76%) and 60 of 128 (47%). The differing prevalence of ACL and MCL tears between the groups was statistically significant (p 0.05). Although kissing contusion was a highly specific sign of ACL tears, its presence was also significant among MCL tears. There was no significant difference in meniscal tears with or without kissing contusion

Serial analysis of gene expression (SAGE)

NARCIS (Netherlands)

van Ruissen, Fred; Baas, Frank

2007-01-01

In 1995, serial analysis of gene expression (SAGE) was developed as a versatile tool for gene expression studies. SAGE technology does not require pre-existing knowledge of the genome that is being examined and therefore SAGE can be applied to many different model systems. In this chapter, the SAGE

An Interactive Database of Cocaine-Responsive Gene Expression

Directory of Open Access Journals (Sweden)

Willard M. Freeman

2002-01-01

Full Text Available The postgenomic era of large-scale gene expression studies is inundating drug abuse researchers and many other scientists with findings related to gene expression. This information is distributed across many different journals, and requires laborious literature searches. Here, we present an interactive database that combines existing information related to cocaine-mediated changes in gene expression in an easy-to-use format. The database is limited to statistically significant changes in mRNA or protein expression after cocaine administration. The Flash-based program is integrated into a Web page, and organizes changes in gene expression based on neuroanatomical region, general function, and gene name. Accompanying each gene is a description of the gene, links to the original publications, and a link to the appropriate OMIM (Online Mendelian Inheritance in Man entry. The nature of this review allows for timely modifications and rapid inclusion of new publications, and should help researchers build second-generation hypotheses on the role of gene expression changes in the physiology and behavior of cocaine abuse. Furthermore, this method of organizing large volumes of scientific information can easily be adapted to assist researchers in fields outside of drug abuse.

CDX2 gene expression in acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Arnaoaut, H.H.; Mokhtar, D.A.; Samy, R.M.; Omar, Sh.A.; Khames, S.A.

2014-01-01

CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR) to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL) at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD) on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

Identification of reference genes in human myelomonocytic cells for gene expression studies in altered gravity.

Science.gov (United States)

Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver

2015-01-01

Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.

Inferring gene networks from discrete expression data

KAUST Repository

Zhang, L.

2013-07-18

The modeling of gene networks from transcriptional expression data is an important tool in biomedical research to reveal signaling pathways and to identify treatment targets. Current gene network modeling is primarily based on the use of Gaussian graphical models applied to continuous data, which give a closedformmarginal likelihood. In this paper,we extend network modeling to discrete data, specifically data from serial analysis of gene expression, and RNA-sequencing experiments, both of which generate counts of mRNAtranscripts in cell samples.We propose a generalized linear model to fit the discrete gene expression data and assume that the log ratios of the mean expression levels follow a Gaussian distribution.We restrict the gene network structures to decomposable graphs and derive the graphs by selecting the covariance matrix of the Gaussian distribution with the hyper-inverse Wishart priors. Furthermore, we incorporate prior network models based on gene ontology information, which avails existing biological information on the genes of interest. We conduct simulation studies to examine the performance of our discrete graphical model and apply the method to two real datasets for gene network inference. © The Author 2013. Published by Oxford University Press. All rights reserved.

Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

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Yu Zhang

2013-12-01

Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

Studying the Complex Expression Dependences between Sets of Coexpressed Genes

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Mario Huerta

2014-01-01

Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

Radiographic joint space narrowing in osteoarthritis of the knee: relationship to meniscal tears and duration of pain

International Nuclear Information System (INIS)

Chan, Wing P.; Huang, Guo-Shu; Hsu, Shu-Mei; Chang, Yue-Cune; Ho, Wei-Pin

2008-01-01

The objective of this study was to assess, with knee radiography, joint space narrowing (JSN) and its relationship to meniscal tears, anterior cruciate ligament (ACL) ruptures, articular cartilage erosion, and duration of pain in patients with knee osteoarthritis. A total of 140 patients who had knee osteoarthritis and underwent primary total knee replacement (TKR) surgery, with unicompartmental medial tibiofemoral JSN (grade 1 or greater) and normal lateral compartments, were recruited. Polytomous logistic regression was used to assess the relationship between JSN and risk factors. All patients with JSN were categorized as grade 1 (n=14, 10.0%), grade 2 (n=64, 45.7%), or grade 3 (n=62, 44.3%). Women presented with indications for a TKR at a younger age than men (mean age, 69 vs 73 years, P<0.05). There were 123 (87.9%) meniscal tears and 58 (41.4%) partial (insufficient or attenuated ACL fibers) and 10 (7.1%) complete ACL ruptures; 115 of 134 (85.8%) patients had moderate to severe cartilage erosion. A higher grade of JSN was correlated with a higher frequency of meniscal tears [odds ratio (OR) 6.00, 95% CI 1.29-27.96 for grade 2 vs grade 1 JSN] and duration of knee pain (OR 1.25, 95% CI 1.01-1.53 for grade 3 vs grade 1 JSN). A higher grade of JSN was not correlated with a higher frequency of ACL rupture or articular cartilage erosion. A higher grade of JSN is associated with a higher frequency of meniscal tears and long duration of knee pain in patients with knee osteoarthritis. (orig.)

Radiographic joint space narrowing in osteoarthritis of the knee: relationship to meniscal tears and duration of pain

Energy Technology Data Exchange (ETDEWEB)

Chan, Wing P. [Taipei Medical University, Department of Radiology, School of Medicine, Taipei (China); Taipei Medical University-Wan Fang Hospital, Department of Radiology, Taipei (China); Huang, Guo-Shu [Tri-Service General Hospital, National Defense Medical Center, Department of Radiology, Taipei (China); Hsu, Shu-Mei [Taipei Medical University, Department of Radiology, School of Medicine, Taipei (China); National Taiwan University, Department of Public Health, Taipei (China); Chang, Yue-Cune [Tamkang University, Department of Mathematics, Taipei County (China); Ho, Wei-Pin [Taipei Medical University-Wan Fang Hospital, Department of Orthopedic Surgery, Taipei (China)

2008-10-15

The objective of this study was to assess, with knee radiography, joint space narrowing (JSN) and its relationship to meniscal tears, anterior cruciate ligament (ACL) ruptures, articular cartilage erosion, and duration of pain in patients with knee osteoarthritis. A total of 140 patients who had knee osteoarthritis and underwent primary total knee replacement (TKR) surgery, with unicompartmental medial tibiofemoral JSN (grade 1 or greater) and normal lateral compartments, were recruited. Polytomous logistic regression was used to assess the relationship between JSN and risk factors. All patients with JSN were categorized as grade 1 (n=14, 10.0%), grade 2 (n=64, 45.7%), or grade 3 (n=62, 44.3%). Women presented with indications for a TKR at a younger age than men (mean age, 69 vs 73 years, P<0.05). There were 123 (87.9%) meniscal tears and 58 (41.4%) partial (insufficient or attenuated ACL fibers) and 10 (7.1%) complete ACL ruptures; 115 of 134 (85.8%) patients had moderate to severe cartilage erosion. A higher grade of JSN was correlated with a higher frequency of meniscal tears [odds ratio (OR) 6.00, 95% CI 1.29-27.96 for grade 2 vs grade 1 JSN] and duration of knee pain (OR 1.25, 95% CI 1.01-1.53 for grade 3 vs grade 1 JSN). A higher grade of JSN was not correlated with a higher frequency of ACL rupture or articular cartilage erosion. A higher grade of JSN is associated with a higher frequency of meniscal tears and long duration of knee pain in patients with knee osteoarthritis. (orig.)

Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer

DEFF Research Database (Denmark)

Jensen, Lars Henrik; Kuramochi, Hidekazu; Crüger, Dorthe Gylling

2011-01-01

promoter was only detected in 14 samples and only at a low level with no correlation to gene expression. MSH2 gene expression was not a prognostic factor for overall survival in univariate or multivariate analysis. The gene expression of MSH2 is a potential quantitative marker ready for further clinical...

Readability of Online Sources Regarding Meniscal Tears.

Science.gov (United States)

Hodax, Jonathan D; Baird, Grayson L; McBride, Trevor; Owens, Brett D

2017-09-01

Meniscal injuries are extremely common, with an incidence of 8.3 per 1,000 person/years in young, active individuals. Patients often turn to the internet to glean information about their injuries, and even to guide decision making about treatment. Much research has been done demonstrating that a reading level of eighth grade or lower is appropriate for accurately communicating written information to patients, yet medical practitioners often fail to meet this requirement. To better examine the information patients receive about meniscal injuries, we set out to evaluate the reading level and content of three commonly used search terms on the three search engines with the largest market share. The authors examined the keywords "meniscus tear," "meniscus tear treatment," and "knee pain meniscus" on the three highest market share search engines. The top 10 results from each search were included, and redundancies identified. Unique Web sites were evaluated for source, word count, reading level, and content including advertisements, diagrams, photographs, nonoperative and operative options, and accurate medical information. A total of 23 unique Web sites were identified in our search, including 13 public education sources, 6 academic institutions, and 4 private physicians/groups. Average grade levels of articles ranged from 9.4 to 14.2 (mean, 11.14; standard deviation [SD] 1.46), and Flesch-Kincaid reading ease scores ranged from 23.9 to 68.7 (mean, 55.31; SD, 10.11). Pages from public sources required the highest level of readability (11.6, 95% confidence interval [CI]: 9.8-13.2), which was significantly higher than private (11.0, 95% CI: 9.3, 12.7]) and academic (10.9, 95% CI: 8.9-12.9), p  = 0.007 and p  = 0.002, respectively. Further efforts to make appropriate health information available to patients are needed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial Periarticular Bursitis in Patients with Osteoarthritis.

Science.gov (United States)

Resorlu, Mustafa; Doner, Davut; Karatag, Ozan; Toprak, Canan Akgun

2017-12-01

This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia patella and medial meniscal tears. Radiological findings of 100 patients undergoing magnetic resonance imaging with a preliminary diagnosis of knee pain were retrospectively evaluated by two radiologists. The first radiologist assessed all patients in terms of osteoarthritis, chondromalacia patella and medial meniscal tear. The second radiologist was blinded to these results and assessed the presence of bursitis in all patients. Mild osteoarthritis (grade I and II) was determined in 55 patients and severe osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed with mild chondromalacia patella (grade I and II) and 46 with severe chondromalacia patella (grade III and IV). Medial meniscus tear was determined in 51 patients. Severe osteoarthritis and chondromalacia patella were positively correlated with meniscal tear (p chondromalacia patella (p = 0.023 and p = 0.479, respectively). Evaluation of lateral compartment bursae revealed lateral collateral ligament bursitis in 2 patients and iliotibial bursitis in 5 patients. We observed a greater prevalence of bursitis in the medial compartment of the knee in patients with severe osteoarthritis and medial meniscus tear.

The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution.

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Jean-François Gout

2010-05-01

Full Text Available The understanding of selective constraints affecting genes is a major issue in biology. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated. Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: the rate of gene losses after whole genome duplications in the Paramecium lineage is negatively correlated to the level of gene expression, and this relationship is not a byproduct of other factors known to affect the fate of gene duplicates. This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: in yeast, we find a clear relationship between gene expression level and the fitness impact of reduction in gene dosage. To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression. This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.

Noise minimization in eukaryotic gene expression.

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Hunter B Fraser

2004-06-01

Full Text Available All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or "noise." Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

Noise minimization in eukaryotic gene expression

Energy Technology Data Exchange (ETDEWEB)

Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

2004-01-15

All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

Noise minimization in eukaryotic gene expression

International Nuclear Information System (INIS)

Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

2004-01-01

All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection

Comparison of SPECT bone scintigraphy with MRI for diagnosis of meniscal tears

International Nuclear Information System (INIS)

Tahmasebi, Mohammad-naghi; Saghari, Mohsen; Moslehi, Masoud; Gholamrezanezhad, Ali

2005-01-01

Scintigraphy has been considered as competitive to MRI, but limited data are available on the accuracy of single photon emission tomography (SPECT) compared with MRI for the assessment of meniscal tears. Our objective was to assess the value of SPECT in comparison to MRI. Between January 2003 and March 2004, sixteen patients were studied with both modalities and the accuracy rates of SPECT scan results, and MRI findings in the diagnosis of meniscal tears were compared. Arthroscopy was the gold standard. The respective sensitivity rate, specificity rate, and positive and negative predictive accuracies of MRI were 89%, 94%, 93%, and 79% and for SPECT those were 78%, 94%, 94%, and 88%. There was good agreement on the presence or absence of tears between two modalities (κ statistic = 0.699). SPECT and MRI are both valuable imaging techniques. SPECT is a useful alternative when MRI is unavailable or unsuitable and it is beneficial when more possible accuracy is desired (such as when MRI results are either inconclusive or conflict with other clinical data)

Positive selection on gene expression in the human brain

DEFF Research Database (Denmark)

Khaitovich, Philipp; Tang, Kun; Franz, Henriette

2006-01-01

Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

Meniscal T1rho and T2 measured with 3.0T MRI increases directly after running a marathon

Energy Technology Data Exchange (ETDEWEB)

Stehling, Christoph [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of Muenster, Department of Clinical Radiology, Muenster (Germany); Luke, Anthony [University of California, Department of Orthopedic Surgery, San Francisco, CA (United States); Stahl, Robert [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Ludwig Maximilians University of Munich, Department of Clinical Radiology, Munich (Germany); Baum, Thomas; Joseph, Gabby; Pan, Judong; Link, Thomas M. [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

2011-06-15

To prospectively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects. Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before, 48-72 h after, and 3 months after competition. Ten controls were examined at baseline and after 3 months. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous. and other knee abnormalities with WORMS scores. Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments. No differences in morphological knee abnormalities were found before and after the marathon. However, all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments (p < 0.0001), which may indicate changes in the biochemical composition of meniscal tissue. While T2 values decreased after 3 months T1rho values remained at a high level, indicating persisting changes in the meniscal matrix composition after a marathon. T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage. T1rho values need further study, but may be a valuable marker for diagnosing early, degenerative changes in the menisci following exercise. (orig.)

A stochastic approach to multi-gene expression dynamics

International Nuclear Information System (INIS)

Ochiai, T.; Nacher, J.C.; Akutsu, T.

2005-01-01

In the last years, tens of thousands gene expression profiles for cells of several organisms have been monitored. Gene expression is a complex transcriptional process where mRNA molecules are translated into proteins, which control most of the cell functions. In this process, the correlation among genes is crucial to determine the specific functions of genes. Here, we propose a novel multi-dimensional stochastic approach to deal with the gene correlation phenomena. Interestingly, our stochastic framework suggests that the study of the gene correlation requires only one theoretical assumption-Markov property-and the experimental transition probability, which characterizes the gene correlation system. Finally, a gene expression experiment is proposed for future applications of the model

Assays for noninvasive imaging of reporter gene expression

International Nuclear Information System (INIS)

Gambhir, S.S.; Barrio, J.R.; Herschman, H.R.; Phelps, M.E.

1999-01-01

Repeated, noninvasive imaging of reporter gene expression is emerging as a valuable tool for monitoring the expression of genes in animals and humans. Monitoring of organ/cell transplantation in living animals and humans, and the assessment of environmental, behavioral, and pharmacologic modulation of gene expression in transgenic animals should soon be possible. The earliest clinical application is likely to be monitoring human gene therapy in tumors transduced with the herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene. Several candidate assays for imaging reporter gene expression have been studied, utilizing cytosine deaminase (CD), HSV1-tk, and dopamine 2 receptor (D2R) as reporter genes. For the HSV1-tk reporter gene, both uracil nucleoside derivatives (e.g., 5-iodo-2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil [FIAU] labeled with 124 I, 131 I ) and acycloguanosine derivatives {e.g., 8-[ 18 F]fluoro-9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (8-[ 18 F]-fluoroganciclovir) ([ 18 F]FGCV), 9-[(3-[ 18 F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG)} have been investigated as reporter probes. For the D2R reporter gene, a derivative of spiperone {3-(2'-[ 18 F]-Fluoroethyl)spiperone ([ 18 F]FESP)} has been used with positron emission tomography (PET) imaging. In this review, the principles and specific assays for imaging reporter gene expression are presented and discussed. Specific examples utilizing adenoviral-mediated delivery of a reporter gene as well as tumors expressing reporter genes are discussed

PRAME gene expression profile in medulloblastoma

Directory of Open Access Journals (Sweden)

Tânia Maria Vulcani-Freitas

2011-02-01

Full Text Available Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84% samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

Systematic identification of human housekeeping genes possibly useful as references in gene expression studies.

Science.gov (United States)

Caracausi, Maria; Piovesan, Allison; Antonaros, Francesca; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara

2017-09-01

The ideal reference, or control, gene for the study of gene expression in a given organism should be expressed at a medium‑high level for easy detection, should be expressed at a constant/stable level throughout different cell types and within the same cell type undergoing different treatments, and should maintain these features through as many different tissues of the organism. From a biological point of view, these theoretical requirements of an ideal reference gene appear to be best suited to housekeeping (HK) genes. Recent advancements in the quality and completeness of human expression microarray data and in their statistical analysis may provide new clues toward the quantitative standardization of human gene expression studies in biology and medicine, both cross‑ and within‑tissue. The systematic approach used by the present study is based on the Transcriptome Mapper tool and exploits the automated reassignment of probes to corresponding genes, intra‑ and inter‑sample normalization, elaboration and representation of gene expression values in linear form within an indexed and searchable database with a graphical interface recording quantitative levels of expression, expression variability and cross‑tissue width of expression for more than 31,000 transcripts. The present study conducted a meta‑analysis of a pool of 646 expression profile data sets from 54 different human tissues and identified actin γ 1 as the HK gene that best fits the combination of all the traditional criteria to be used as a reference gene for general use; two ribosomal protein genes, RPS18 and RPS27, and one aquaporin gene, POM121 transmembrane nucleporin C, were also identified. The present study provided a list of tissue‑ and organ‑specific genes that may be most suited for the following individual tissues/organs: Adipose tissue, bone marrow, brain, heart, kidney, liver, lung, ovary, skeletal muscle and testis; and also provides in these cases a representative

SIGNATURE: A workbench for gene expression signature analysis

Directory of Open Access Journals (Sweden)

Chang Jeffrey T

2011-11-01

Full Text Available Abstract Background The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise. Results We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses Bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access. Conclusions SIGNATURE is available for public use at http://genepattern.genome.duke.edu/signature/.

Mining gene expression data of multiple sclerosis.

Directory of Open Access Journals (Sweden)

Pi Guo

Full Text Available Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example.Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models' performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined.An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score.The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases.

Plasticity-Related Gene Expression During Eszopiclone-Induced Sleep.

Science.gov (United States)

Gerashchenko, Dmitry; Pasumarthi, Ravi K; Kilduff, Thomas S

2017-07-01

Experimental evidence suggests that restorative processes depend on synaptic plasticity changes in the brain during sleep. We used the expression of plasticity-related genes to assess synaptic plasticity changes during drug-induced sleep. We first characterized sleep induced by eszopiclone in mice during baseline conditions and during the recovery from sleep deprivation. We then compared the expression of 18 genes and two miRNAs critically involved in synaptic plasticity in these mice. Gene expression was assessed in the cerebral cortex and hippocampus by the TaqMan reverse transcription polymerase chain reaction and correlated with sleep parameters. Eszopiclone reduced the latency to nonrapid eye movement (NREM) sleep and increased NREM sleep amounts. Eszopiclone had no effect on slow wave activity (SWA) during baseline conditions but reduced the SWA increase during recovery sleep (RS) after sleep deprivation. Gene expression analyses revealed three distinct patterns: (1) four genes had higher expression either in the cortex or hippocampus in the group of mice with increased amounts of wakefulness; (2) a large proportion of plasticity-related genes (7 out of 18 genes) had higher expression during RS in the cortex but not in the hippocampus; and (3) six genes and the two miRNAs showed no significant changes across conditions. Even at a relatively high dose (20 mg/kg), eszopiclone did not reduce the expression of plasticity-related genes during RS period in the cortex. These results indicate that gene expression associated with synaptic plasticity occurs in the cortex in the presence of a hypnotic medication. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Evaluation of suitable reference genes for gene expression studies in bovine muscular tissue

Directory of Open Access Journals (Sweden)

Dunner Susana

2008-09-01

Full Text Available Abstract Background Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RTqPCR is a technique used to measure mRNA species copy number as a way to determine key genes involved in different biological processes. However, the expression level of these key genes may vary among tissues or cells not only as a consequence of differential expression but also due to different factors, including choice of reference genes to normalize the expression levels of the target genes; thus the selection of reference genes is critical for expression studies. For this purpose, ten candidate reference genes were investigated in bovine muscular tissue. Results The value of stability of ten candidate reference genes included in three groups was estimated: the so called 'classical housekeeping' genes (18S, GAPDH and ACTB, a second set of genes used in expression studies conducted on other tissues (B2M, RPII, UBC and HMBS and a third set of novel genes (SF3A1, EEF1A2 and CASC3. Three different statistical algorithms were used to rank the genes by their stability measures as produced by geNorm, NormFinder and Bestkeeper. The three methods tend to agree on the most stably expressed genes and the least in muscular tissue. EEF1A2 and HMBS followed by SF3A1, ACTB, and CASC3 can be considered as stable reference genes, and B2M, RPII, UBC and GAPDH would not be appropriate. Although the rRNA-18S stability measure seems to be within the range of acceptance, its use is not recommended because its synthesis regulation is not representative of mRNA levels. Conclusion Based on geNorm algorithm, we propose the use of three genes SF3A1, EEF1A2 and HMBS as references for normalization of real-time RTqPCR in muscle expression studies.

Expression profiling identifies genes involved in emphysema severity

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Bowman Rayleen V

2009-09-01

Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients. Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples. Class comparison identified 98 differentially expressed genes (p p Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.

Decoupling Linear and Nonlinear Associations of Gene Expression

KAUST Repository

Itakura, Alan

2013-05-01

The FANTOM consortium has generated a large gene expression dataset of different cell lines and tissue cultures using the single-molecule sequencing technology of HeliscopeCAGE. This provides a unique opportunity to investigate novel associations between gene expression over time and different cell types. Here, we create a MatLab wrapper for a powerful and computationally intensive set of statistics known as Maximal Information Coefficient, and then calculate this statistic for a large, comprehensive dataset containing gene expression of a variety of differentiating tissues. We then distinguish between linear and nonlinear associations, and then create gene association networks. Following this analysis, we are then able to identify clusters of linear gene associations that then associate nonlinearly with other clusters of linearity, providing insight to much more complex connections between gene expression patterns than previously anticipated.

Decoupling Linear and Nonlinear Associations of Gene Expression

KAUST Repository

Itakura, Alan

2013-01-01

The FANTOM consortium has generated a large gene expression dataset of different cell lines and tissue cultures using the single-molecule sequencing technology of HeliscopeCAGE. This provides a unique opportunity to investigate novel associations between gene expression over time and different cell types. Here, we create a MatLab wrapper for a powerful and computationally intensive set of statistics known as Maximal Information Coefficient, and then calculate this statistic for a large, comprehensive dataset containing gene expression of a variety of differentiating tissues. We then distinguish between linear and nonlinear associations, and then create gene association networks. Following this analysis, we are then able to identify clusters of linear gene associations that then associate nonlinearly with other clusters of linearity, providing insight to much more complex connections between gene expression patterns than previously anticipated.

Genetic architecture of gene expression in the chicken

Directory of Open Access Journals (Sweden)

Stanley Dragana

2013-01-01

Full Text Available Abstract Background The annotation of many genomes is limited, with a large proportion of identified genes lacking functional assignments. The construction of gene co-expression networks is a powerful approach that presents a way of integrating information from diverse gene expression datasets into a unified analysis which allows inferences to be drawn about the role of previously uncharacterised genes. Using this approach, we generated a condition-free gene co-expression network for the chicken using data from 1,043 publically available Affymetrix GeneChip Chicken Genome Arrays. This data was generated from a diverse range of experiments, including different tissues and experimental conditions. Our aim was to identify gene co-expression modules and generate a tool to facilitate exploration of the functional chicken genome. Results Fifteen modules, containing between 24 and 473 genes, were identified in the condition-free network. Most of the modules showed strong functional enrichment for particular Gene Ontology categories. However, a few showed no enrichment. Transcription factor binding site enrichment was also noted. Conclusions We have demonstrated that this chicken gene co-expression network is a useful tool in gene function prediction and the identification of putative novel transcription factors and binding sites. This work highlights the relevance of this methodology for functional prediction in poorly annotated genomes such as the chicken.

Biomechanical testing of new meniscal repair techniques containing ultra high-molecular weight polyethylene suture.

Science.gov (United States)

Barber, F Alan; Herbert, Morley A; Schroeder, F Alexander; Aziz-Jacobo, Jorge; Sutker, Michael J

2009-09-01

To evaluate the biomechanical characteristics of current meniscal repair techniques containing ultra high-molecular weight polyethylene (UHMWPE) suture with and without cyclic loading. Vertical longitudinal cuts made in porcine menisci were secured with a single repair device. Noncycled and cycled (500 cycles) biomechanical tests were performed on the following groups: group 1, No. 2-0 Mersilene vertical suture (Ethicon, Somerville, NJ); group 2, No. 2-0 Orthocord vertical suture (DePuy Mitek, Westwood, MA); group 3, No. 0 Ultrabraid vertical suture (Smith & Nephew Endoscopy, Andover, MA); group 4, No. 2-0 FiberWire vertical suture (Arthrex, Naples, FL); group 5, vertically oriented mattress suture by use of an Ultra FasT-Fix device (Smith & Nephew Endoscopy) with No. 0 Ultrabraid; group 6, vertically oriented mattress suture by use of a RapidLoc A2 device (DePuy Mitek) with No. 2-0 Orthocord suture; group 7, vertically oriented stitch by use of a MaxFire device with MaxBraid PE suture (Biomet Sports Medicine, Warsaw, IN); and group 8, an obliquely oriented stitch of No. 0 UHMWPE suture inserted by use of a CrossFix device (Cayenne Medical, Scottsdale, AZ). Endpoints were failure loads, failure modes, stiffness, and cyclic displacement. Mean single-pull loads were calculated for Ultra FasT-Fix (121 N), FiberWire (110 N), MaxFire (130 N), Mersilene (84 N), Orthocord (124 N), RapidLoc A2 (86 N), CrossFix (77 N), and Ultrabraid (109 N). After 500 cyclic loads, the Orthocord (222 N) repair was stronger than the others: Ultra FasT-Fix (110 N), FiberWire (117 N), MaxFire (132 N), Mersilene (89 N), RapidLoc A2 (108 N), CrossFix (95 N), and Ultrabraid (126 N) (P Fix, RapidLoc A2, and MaxFire) were comparable to the isolated UHMWPE-containing suture repairs on single-failure load testing. UHMWPE-containing suture repairs are stronger than braided polyester suture repairs, but pure UHMWPE suture (Ultrabraid) elongated more during cycling. Orthocord suture is significantly

Bayesian assignment of gene ontology terms to gene expression experiments

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Sykacek, P.

2012-01-01

Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

Bayesian assignment of gene ontology terms to gene expression experiments.

Science.gov (United States)

Sykacek, P

2012-09-15

Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.

Gene expression profile data for mouse facial development

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Sonia M. Leach

2017-08-01

Full Text Available This article contains data related to the research articles "Spatial and Temporal Analysis of Gene Expression during Growth and Fusion of the Mouse Facial Prominences" (Feng et al., 2009 [1] and “Systems Biology of facial development: contributions of ectoderm and mesenchyme” (Hooper et al., 2017 In press [2]. Embryonic mammalian craniofacial development is a complex process involving the growth, morphogenesis, and fusion of distinct facial prominences into a functional whole. Aberrant gene regulation during this process can lead to severe craniofacial birth defects, including orofacial clefting. As a means to understand the genes involved in facial development, we had previously dissected the embryonic mouse face into distinct prominences: the mandibular, maxillary or nasal between E10.5 and E12.5. The prominences were then processed intact, or separated into ectoderm and mesenchyme layers, prior analysis of RNA expression using microarrays (Feng et al., 2009, Hooper et al., 2017 in press [1,2]. Here, individual gene expression profiles have been built from these datasets that illustrate the timing of gene expression in whole prominences or in the separated tissue layers. The data profiles are presented as an indexed and clickable list of the genes each linked to a graphical image of that gene׳s expression profile in the ectoderm, mesenchyme, or intact prominence. These data files will enable investigators to obtain a rapid assessment of the relative expression level of any gene on the array with respect to time, tissue, prominence, and expression trajectory.

Integrated olfactory receptor and microarray gene expression databases

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Crasto Chiquito J

2007-06-01

Full Text Available Abstract Background Gene expression patterns of olfactory receptors (ORs are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD to house OR gene expression data. ORMD is integrated with the Olfactory Receptor Database (ORDB, which is a key repository of OR gene information. Both databases aim to aid experimental research related to olfaction. Description ORMD is a Web-accessible database that provides a secure data repository for OR microarray experiments. It contains both publicly available and private data; accessing the latter requires authenticated login. The ORMD is designed to allow users to not only deposit gene expression data but also manage their projects/experiments. For example, contributors can choose whether to make their datasets public. For each experiment, users can download the raw data files and view and export the gene expression data. For each OR gene being probed in a microarray experiment, a hyperlink to that gene in ORDB provides access to genomic and proteomic information related to the corresponding olfactory receptor. Individual ORs archived in ORDB are also linked to ORMD, allowing users access to the related microarray gene expression data. Conclusion ORMD serves as a data repository and project management system. It facilitates the study of microarray experiments of gene expression in the olfactory system. In conjunction with ORDB, ORMD integrates gene expression data with the genomic and functional data of ORs, and is thus a useful resource for both olfactory researchers and the public.

Gene expression analysis of flax seed development

Science.gov (United States)

2011-01-01

Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages) seed coats (globular and torpedo stages) and endosperm (pooled globular to torpedo stages) and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST) (GenBank accessions LIBEST_026995 to LIBEST_027011) were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152) had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid clones that comprise

Gene expression analysis of flax seed development

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Sharpe Andrew

2011-04-01

Full Text Available Abstract Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages seed coats (globular and torpedo stages and endosperm (pooled globular to torpedo stages and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST (GenBank accessions LIBEST_026995 to LIBEST_027011 were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152 had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid

Supplementary Material for: Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

2015-01-01

Abstract Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis

Identification of suitable reference genes for gene expression studies of shoulder instability.

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Mariana Ferreira Leal

Full Text Available Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results. In the present study, we evaluated the suitability of a set of reference genes using samples from the glenohumeral capsules of individuals with and without shoulder instability. We analyzed the expression of six commonly used reference genes (ACTB, B2M, GAPDH, HPRT1, TBP and TFRC in the antero-inferior, antero-superior and posterior portions of the glenohumeral capsules of cases and controls. The stability of the candidate reference gene expression was determined using four software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1 was the best single reference gene, and HPRT1 and B2M composed the best pair of reference genes from different analysis groups, including simultaneous analysis of all tissue samples. GenEx software was used to identify the optimal number of reference genes to be used for normalization and demonstrated that the accumulated standard deviation resulting from the use of 2 reference genes was similar to that resulting from the use of 3 or more reference genes. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1. Although the use of different reference gene combinations yielded variable normalized quantities, the relative quantities within sample groups were similar and confirmed that no obvious differences were observed when using 2, 3 or 4 reference genes. Consequently, the use of 2 stable reference genes for normalization, especially

Detecting microRNA activity from gene expression data

LENUS (Irish Health Repository)

Madden, Stephen F

2010-05-18

Abstract Background MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions. Results Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance. Conclusions We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.

Detecting microRNA activity from gene expression data.

LENUS (Irish Health Repository)

Madden, Stephen F

2010-01-01

BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions. RESULTS: Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance. CONCLUSIONS: We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.

Gene expression results in lipopolysaccharide-stimulated monocytes depend significantly on the choice of reference genes

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Øvstebø Reidun

2010-05-01

Full Text Available Abstract Background Gene expression in lipopolysaccharide (LPS-stimulated monocytes is mainly studied by quantitative real-time reverse transcription PCR (RT-qPCR using GAPDH (glyceraldehyde 3-phosphate dehydrogenase or ACTB (beta-actin as reference gene for normalization. Expression of traditional reference genes has been shown to vary substantially under certain conditions leading to invalid results. To investigate whether traditional reference genes are stably expressed in LPS-stimulated monocytes or if RT-qPCR results are dependent on the choice of reference genes, we have assessed and evaluated gene expression stability of twelve candidate reference genes in this model system. Results Twelve candidate reference genes were quantified by RT-qPCR in LPS-stimulated, human monocytes and evaluated using the programs geNorm, Normfinder and BestKeeper. geNorm ranked PPIB (cyclophilin B, B2M (beta-2-microglobulin and PPIA (cyclophilin A as the best combination for gene expression normalization in LPS-stimulated monocytes. Normfinder suggested TBP (TATA-box binding protein and B2M as the best combination. Compared to these combinations, normalization using GAPDH alone resulted in significantly higher changes of TNF-α (tumor necrosis factor-alpha and IL10 (interleukin 10 expression. Moreover, a significant difference in TNF-α expression between monocytes stimulated with equimolar concentrations of LPS from N. meningitides and E. coli, respectively, was identified when using the suggested combinations of reference genes for normalization, but stayed unrecognized when employing a single reference gene, ACTB or GAPDH. Conclusions Gene expression levels in LPS-stimulated monocytes based on RT-qPCR results differ significantly when normalized to a single gene or a combination of stably expressed reference genes. Proper evaluation of reference gene stabiliy is therefore mandatory before reporting RT-qPCR results in LPS-stimulated monocytes.

Differentially expressed genes in iron-induced prion protein conversion

International Nuclear Information System (INIS)

Kim, Minsun; Kim, Eun-hee; Choi, Bo-Ran; Woo, Hee-Jong

2016-01-01

The conversion of the cellular prion protein (PrP C ) to the protease-resistant isoform is the key event in chronic neurodegenerative diseases, including transmissible spongiform encephalopathies (TSEs). Increased iron in prion-related disease has been observed due to the prion protein-ferritin complex. Additionally, the accumulation and conversion of recombinant PrP (rPrP) is specifically derived from Fe(III) but not Fe(II). Fe(III)-mediated PK-resistant PrP (PrP res ) conversion occurs within a complex cellular environment rather than via direct contact between rPrP and Fe(III). In this study, differentially expressed genes correlated with prion degeneration by Fe(III) were identified using Affymetrix microarrays. Following Fe(III) treatment, 97 genes were differentially expressed, including 85 upregulated genes and 12 downregulated genes (≥1.5-fold change in expression). However, Fe(II) treatment produced moderate alterations in gene expression without inducing dramatic alterations in gene expression profiles. Moreover, functional grouping of identified genes indicated that the differentially regulated genes were highly associated with cell growth, cell maintenance, and intra- and extracellular transport. These findings showed that Fe(III) may influence the expression of genes involved in PrP folding by redox mechanisms. The identification of genes with altered expression patterns in neural cells may provide insights into PrP conversion mechanisms during the development and progression of prion-related diseases. - Highlights: • Differential genes correlated with prion degeneration by Fe(III) were identified. • Genes were identified in cell proliferation and intra- and extracellular transport. • In PrP degeneration, redox related genes were suggested. • Cbr2, Rsad2, Slc40a1, Amph and Mvd were expressed significantly.

Regulation of meiotic gene expression in plants

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Adele eZhou

2014-08-01

Full Text Available With the recent advances in genomics and sequencing technologies, databases of transcriptomes representing many cellular processes have been built. Meiotic transcriptomes in plants have been studied in Arabidopsis thaliana, rice (Oryza sativa, wheat (Triticum aestivum, petunia (Petunia hybrida, sunflower (Helianthus annuus, and maize (Zea mays. Studies in all organisms, but particularly in plants, indicate that a very large number of genes are expressed during meiosis, though relatively few of them seem to be required for the completion of meiosis. In this review, we focus on gene expression at the RNA level and analyze the meiotic transcriptome datasets and explore expression patterns of known meiotic genes to elucidate how gene expression could be regulated during meiosis. We also discuss mechanisms, such as chromatin organization and non-coding RNAs, that might be involved in the regulation of meiotic transcription patterns.

Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data

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Tintle Nathan L

2012-08-01

Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.

Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

Science.gov (United States)

Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

2017-08-01

This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Evaluation of Appropriate Reference Genes for Gene Expression Normalization during Watermelon Fruit Development.

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Qiusheng Kong

Full Text Available Gene expression analysis in watermelon (Citrullus lanatus fruit has drawn considerable attention with the availability of genome sequences to understand the regulatory mechanism of fruit development and to improve its quality. Real-time quantitative reverse-transcription PCR (qRT-PCR is a routine technique for gene expression analysis. However, appropriate reference genes for transcript normalization in watermelon fruits have not been well characterized. The aim of this study was to evaluate the appropriateness of 12 genes for their potential use as reference genes in watermelon fruits. Expression variations of these genes were measured in 48 samples obtained from 12 successive developmental stages of parthenocarpic and fertilized fruits of two watermelon genotypes by using qRT-PCR analysis. Considering the effects of genotype, fruit setting method, and developmental stage, geNorm determined clathrin adaptor complex subunit (ClCAC, β-actin (ClACT, and alpha tubulin 5 (ClTUA5 as the multiple reference genes in watermelon fruit. Furthermore, ClCAC alone or together with SAND family protein (ClSAND was ranked as the single or two best reference genes by NormFinder. By using the top-ranked reference genes to normalize the transcript abundance of phytoene synthase (ClPSY1, a good correlation between lycopene accumulation and ClPSY1 expression pattern was observed in ripening watermelon fruit. These validated reference genes will facilitate the accurate measurement of gene expression in the studies on watermelon fruit biology.

Evaluation of Appropriate Reference Genes for Gene Expression Normalization during Watermelon Fruit Development.

Science.gov (United States)

Kong, Qiusheng; Yuan, Jingxian; Gao, Lingyun; Zhao, Liqiang; Cheng, Fei; Huang, Yuan; Bie, Zhilong

2015-01-01

Gene expression analysis in watermelon (Citrullus lanatus) fruit has drawn considerable attention with the availability of genome sequences to understand the regulatory mechanism of fruit development and to improve its quality. Real-time quantitative reverse-transcription PCR (qRT-PCR) is a routine technique for gene expression analysis. However, appropriate reference genes for transcript normalization in watermelon fruits have not been well characterized. The aim of this study was to evaluate the appropriateness of 12 genes for their potential use as reference genes in watermelon fruits. Expression variations of these genes were measured in 48 samples obtained from 12 successive developmental stages of parthenocarpic and fertilized fruits of two watermelon genotypes by using qRT-PCR analysis. Considering the effects of genotype, fruit setting method, and developmental stage, geNorm determined clathrin adaptor complex subunit (ClCAC), β-actin (ClACT), and alpha tubulin 5 (ClTUA5) as the multiple reference genes in watermelon fruit. Furthermore, ClCAC alone or together with SAND family protein (ClSAND) was ranked as the single or two best reference genes by NormFinder. By using the top-ranked reference genes to normalize the transcript abundance of phytoene synthase (ClPSY1), a good correlation between lycopene accumulation and ClPSY1 expression pattern was observed in ripening watermelon fruit. These validated reference genes will facilitate the accurate measurement of gene expression in the studies on watermelon fruit biology.

Novel gene sets improve set-level classification of prokaryotic gene expression data.

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Holec, Matěj; Kuželka, Ondřej; Železný, Filip

2015-10-28

Set-level classification of gene expression data has received significant attention recently. In this setting, high-dimensional vectors of features corresponding to genes are converted into lower-dimensional vectors of features corresponding to biologically interpretable gene sets. The dimensionality reduction brings the promise of a decreased risk of overfitting, potentially resulting in improved accuracy of the learned classifiers. However, recent empirical research has not confirmed this expectation. Here we hypothesize that the reported unfavorable classification results in the set-level framework were due to the adoption of unsuitable gene sets defined typically on the basis of the Gene ontology and the KEGG database of metabolic networks. We explore an alternative approach to defining gene sets, based on regulatory interactions, which we expect to collect genes with more correlated expression. We hypothesize that such more correlated gene sets will enable to learn more accurate classifiers. We define two families of gene sets using information on regulatory interactions, and evaluate them on phenotype-classification tasks using public prokaryotic gene expression data sets. From each of the two gene-set families, we first select the best-performing subtype. The two selected subtypes are then evaluated on independent (testing) data sets against state-of-the-art gene sets and against the conventional gene-level approach. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. Novel gene sets defined on the basis of regulatory interactions improve set-level classification of gene expression data. The experimental scripts and other material needed to reproduce the experiments are available at http://ida.felk.cvut.cz/novelgenesets.tar.gz.

Differential neutrophil gene expression in early bovine pregnancy

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Kizaki Keiichiro

2013-02-01

Full Text Available Abstract Background In food production animals, especially cattle, the diagnosis of gestation is important because the timing of gestation directly affects the running of farms. Various methods have been used to detect gestation, but none of them are ideal because of problems with the timing of detection or the accuracy, simplicity, or cost of the method. A new method for detecting gestation, which involves assessing interferon-tau (IFNT-stimulated gene expression in peripheral blood leukocytes (PBL, was recently proposed. PBL fractionation methods were used to examine whether the expression profiles of various PBL populations could be used as reliable diagnostic markers of bovine gestation. Methods PBL were collected on days 0 (just before artificial insemination, 7, 14, 17, 21, and 28 of gestation. The gene expression levels of the PBL were assessed with microarray analysis and/or quantitative real-time reverse transcription (q PCR. PBL fractions were collected by flow cytometry or density gradient cell separation using Histopaque 1083 or Ficoll-Conray solutions. The expression levels of four IFNT-stimulated genes, interferon-stimulated protein 15 kDa (ISG15, myxovirus-resistance (MX 1 and 2, and 2′-5′-oligoadenylate synthetase (OAS1, were then analyzed in each fraction through day 28 of gestation using qPCR. Results Microarray analysis detected 72 and 28 genes in whole PBL that were significantly higher on days 14 and 21 of gestation, respectively, than on day 0. The upregulated genes included IFNT-stimulated genes. The expression levels of these genes increased with the progression of gestation until day 21. In flow cytometry experiments, on day 14 the expression levels of all of the genes were significantly higher in the granulocyte fraction than in the other fractions. Their expression gradually decreased through day 28 of gestation. Strong correlations were observed between the expression levels of the four genes in the granulocyte

Validation of suitable reference genes for quantitative gene expression analysis in Panax ginseng

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Meizhen eWang

2016-01-01

Full Text Available Reverse transcription-qPCR (RT-qPCR has become a popular method for gene expression studies. Its results require data normalization by housekeeping genes. No single gene is proved to be stably expressed under all experimental conditions. Therefore, systematic evaluation of reference genes is necessary. With the aim to identify optimum reference genes for RT-qPCR analysis of gene expression in different tissues of Panax ginseng and the seedlings grown under heat stress, we investigated the expression stability of eight candidate reference genes, including elongation factor 1-beta (EF1-β, elongation factor 1-gamma (EF1-γ, eukaryotic translation initiation factor 3G (IF3G, eukaryotic translation initiation factor 3B (IF3B, actin (ACT, actin11 (ACT11, glyceraldehyde-3-phosphate dehydrogenase (GAPDH and cyclophilin ABH-like protein (CYC, using four widely used computational programs: geNorm, Normfinder, BestKeeper, and the comparative ΔCt method. The results were then integrated using the web-based tool RefFinder. As a result, EF1-γ, IF3G and EF1-β were the three most stable genes in different tissues of P. ginseng, while IF3G, ACT11 and GAPDH were the top three-ranked genes in seedlings treated with heat. Using three better reference genes alone or in combination as internal control, we examined the expression profiles of MAR, a multiple function-associated mRNA-like non-coding RNA (mlncRNA in P. ginseng. Taken together, we recommended EF1-γ/IF3G and IF3G/ACT11 as the suitable pair of reference genes for RT-qPCR analysis of gene expression in different tissues of P. ginseng and the seedlings grown under heat stress, respectively. The results serve as a foundation for future studies on P. ginseng functional genomics.

Identification of differentially expressed genes in flax (Linum usitatissimum L.) under saline-alkaline stress by digital gene expression.

Science.gov (United States)

Yu, Ying; Huang, Wengong; Chen, Hongyu; Wu, Guangwen; Yuan, Hongmei; Song, Xixia; Kang, Qinghua; Zhao, Dongsheng; Jiang, Weidong; Liu, Yan; Wu, Jianzhong; Cheng, Lili; Yao, Yubo; Guan, Fengzhi

2014-10-01

The salinization and alkalization of soil are widespread environmental problems, and alkaline salt stress is more destructive than neutral salt stress. Therefore, understanding the mechanism of plant tolerance to saline-alkaline stress has become a major challenge. However, little attention has been paid to the mechanism of plant alkaline salt tolerance. In this study, gene expression profiling of flax was analyzed under alkaline-salt stress (AS2), neutral salt stress (NSS) and alkaline stress (AS) by digital gene expression. Three-week-old flax seedlings were placed in 25 mM Na2CO3 (pH11.6) (AS2), 50mM NaCl (NSS) and NaOH (pH11.6) (AS) for 18 h. There were 7736, 1566 and 454 differentially expressed genes in AS2, NSS and AS compared to CK, respectively. The GO category gene enrichment analysis revealed that photosynthesis was particularly affected in AS2, carbohydrate metabolism was particularly affected in NSS, and the response to biotic stimulus was particularly affected in AS. We also analyzed the expression pattern of five categories of genes including transcription factors, signaling transduction proteins, phytohormones, reactive oxygen species proteins and transporters under these three stresses. Some key regulatory gene families involved in abiotic stress, such as WRKY, MAPKKK, ABA, PrxR and ion channels, were differentially expressed. Compared with NSS and AS, AS2 triggered more differentially expressed genes and special pathways, indicating that the mechanism of AS2 was more complex than NSS and AS. To the best of our knowledge, this was the first transcriptome analysis of flax in response to saline-alkaline stress. These data indicate that common and diverse features of saline-alkaline stress provide novel insights into the molecular mechanisms of plant saline-alkaline tolerance and offer a number of candidate genes as potential markers of tolerance to saline-alkaline stress. Copyright © 2014 Elsevier B.V. All rights reserved.

The contribution of 3D quantitative meniscal and cartilage measures to variation in normal radiographic joint space width—Data from the Osteoarthritis Initiative healthy reference cohort

International Nuclear Information System (INIS)

Roth, Melanie; Wirth, Wolfgang; Emmanuel, Katja; Culvenor, Adam G.; Eckstein, Felix

2017-01-01

Objective: To explore to what extent three-dimensional measures of the meniscus and femorotibial cartilage explain the variation in medial and lateral femorotibial radiographic joint space width (JSW), in healthy men and women. Methods: The right knees of 87 Osteoarthritis Initiative healthy reference participants (no symptoms, radiographic signs or risk factors of osteoarthritis; 37 men, 50 women; age 55.0 ± 7.6; BMI 24.4 ± 3.1) were assessed. Quantitative measures of subregional femorotibial cartilage thickness and meniscal position and morphology were computed from segmented magnetic resonance images. Minimal and medial/lateral fixed-location JSW were determined from fixed-flexion radiographs. Correlation and regression analyses were used to explore the contribution of demographic, cartilage and meniscal parameters to JSW in healthy subjects. Results: The correlation with (medial) minimal JSW was somewhat stronger for cartilage thickness (0.54 ≤ r ≤ 0.67) than for meniscal (−0.31 ≤ r ≤ 0.50) or demographic measures (−0.15 ≤ r ≤ 0.48), in particular in men. In women, in contrast, the strength of the correlations of cartilage thickness and meniscal measures with minimal JSW were in the same range. Fixed-location JSW measures showed stronger correlations with cartilage thickness (r ≥ 0.68 medially; r ≥ 0.59 laterally) than with meniscal measures (r ≤ |0.32| medially; r ≤ |0.32| laterally). Stepwise regression models revealed that meniscal measures added significant independent information to the total variance explained in minimal JSW (adjusted multiple r 2 = 58%) but not in medial or lateral fixed-location JSW (r 2 = 60/51%, respectively). Conclusions: In healthy subjects, minimal JSW was observed to reflect a combination of cartilage and meniscal measures, particularly in women. Fixed-location JSW, in contrast, was found to be dominated by variance in cartilage thickness in both men and women, with somewhat higher correlations between

Improved gene expression signature of testicular carcinoma in situ

DEFF Research Database (Denmark)

Almstrup, Kristian; Leffers, Henrik; Lothe, Ragnhild A

2007-01-01

on global gene expression in testicular CIS have been previously published. We have merged the two data sets on CIS samples (n = 6) and identified the shared gene expression signature in relation to expression in normal testis. Among the top-20 highest expressed genes, one-third was transcription factors...... development' were significantly altered and could collectively affect cellular pathways like the WNT signalling cascade, which thus may be disrupted in testicular CIS. The merged CIS data from two different microarray platforms, to our knowledge, provide the most precise CIS gene expression signature to date....

The gsdf gene locus harbors evolutionary conserved and clustered genes preferentially expressed in fish previtellogenic oocytes.

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Gautier, Aude; Le Gac, Florence; Lareyre, Jean-Jacques

2011-02-01

The gonadal soma-derived factor (GSDF) belongs to the transforming growth factor-β superfamily and is conserved in teleostean fish species. Gsdf is specifically expressed in the gonads, and gene expression is restricted to the granulosa and Sertoli cells in trout and medaka. The gsdf gene expression is correlated to early testis differentiation in medaka and was shown to stimulate primordial germ cell and spermatogonia proliferation in trout. In the present study, we show that the gsdf gene localizes to a syntenic chromosomal fragment conserved among vertebrates although no gsdf-related gene is detected on the corresponding genomic region in tetrapods. We demonstrate using quantitative RT-PCR that most of the genes localized in the synteny are specifically expressed in medaka gonads. Gsdf is the only gene of the synteny with a much higher expression in the testis compared to the ovary. In contrast, gene expression pattern analysis of the gsdf surrounding genes (nup54, aff1, klhl8, sdad1, and ptpn13) indicates that these genes are preferentially expressed in the female gonads. The tissue distribution of these genes is highly similar in medaka and zebrafish, two teleostean species that have diverged more than 110 million years ago. The cellular localization of these genes was determined in medaka gonads using the whole-mount in situ hybridization technique. We confirm that gsdf gene expression is restricted to Sertoli and granulosa cells in contact with the premeiotic and meiotic cells. The nup54 gene is expressed in spermatocytes and previtellogenic oocytes. Transcripts corresponding to the ovary-specific genes (aff1, klhl8, and sdad1) are detected only in previtellogenic oocytes. No expression was detected in the gonocytes in 10 dpf embryos. In conclusion, we show that the gsdf gene localizes to a syntenic chromosomal fragment harboring evolutionary conserved genes in vertebrates. These genes are preferentially expressed in previtelloogenic oocytes, and thus, they

Selection of reference genes for quantitative gene expression normalization in flax (Linum usitatissimum L.

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Neutelings Godfrey

2010-04-01

Full Text Available Abstract Background Quantitative real-time PCR (qRT-PCR is currently the most accurate method for detecting differential gene expression. Such an approach depends on the identification of uniformly expressed 'housekeeping genes' (HKGs. Extensive transcriptomic data mining and experimental validation in different model plants have shown that the reliability of these endogenous controls can be influenced by the plant species, growth conditions and organs/tissues examined. It is therefore important to identify the best reference genes to use in each biological system before using qRT-PCR to investigate differential gene expression. In this paper we evaluate different candidate HKGs for developmental transcriptomic studies in the economically-important flax fiber- and oil-crop (Linum usitatissimum L. Results Specific primers were designed in order to quantify the expression levels of 20 different potential housekeeping genes in flax roots, internal- and external-stem tissues, leaves and flowers at different developmental stages. After calculations of PCR efficiencies, 13 HKGs were retained and their expression stabilities evaluated by the computer algorithms geNorm and NormFinder. According to geNorm, 2 Transcriptional Elongation Factors (TEFs and 1 Ubiquitin gene are necessary for normalizing gene expression when all studied samples are considered. However, only 2 TEFs are required for normalizing expression in stem tissues. In contrast, NormFinder identified glyceraldehyde-3-phosphate dehydrogenase (GADPH as the most stably expressed gene when all samples were grouped together, as well as when samples were classed into different sub-groups. qRT-PCR was then used to investigate the relative expression levels of two splice variants of the flax LuMYB1 gene (homologue of AtMYB59. LuMYB1-1 and LuMYB1-2 were highly expressed in the internal stem tissues as compared to outer stem tissues and other samples. This result was confirmed with both ge

Selection of reference genes for quantitative gene expression normalization in flax (Linum usitatissimum L.).

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Huis, Rudy; Hawkins, Simon; Neutelings, Godfrey

2010-04-19

Quantitative real-time PCR (qRT-PCR) is currently the most accurate method for detecting differential gene expression. Such an approach depends on the identification of uniformly expressed 'housekeeping genes' (HKGs). Extensive transcriptomic data mining and experimental validation in different model plants have shown that the reliability of these endogenous controls can be influenced by the plant species, growth conditions and organs/tissues examined. It is therefore important to identify the best reference genes to use in each biological system before using qRT-PCR to investigate differential gene expression. In this paper we evaluate different candidate HKGs for developmental transcriptomic studies in the economically-important flax fiber- and oil-crop (Linum usitatissimum L). Specific primers were designed in order to quantify the expression levels of 20 different potential housekeeping genes in flax roots, internal- and external-stem tissues, leaves and flowers at different developmental stages. After calculations of PCR efficiencies, 13 HKGs were retained and their expression stabilities evaluated by the computer algorithms geNorm and NormFinder. According to geNorm, 2 Transcriptional Elongation Factors (TEFs) and 1 Ubiquitin gene are necessary for normalizing gene expression when all studied samples are considered. However, only 2 TEFs are required for normalizing expression in stem tissues. In contrast, NormFinder identified glyceraldehyde-3-phosphate dehydrogenase (GADPH) as the most stably expressed gene when all samples were grouped together, as well as when samples were classed into different sub-groups.qRT-PCR was then used to investigate the relative expression levels of two splice variants of the flax LuMYB1 gene (homologue of AtMYB59). LuMYB1-1 and LuMYB1-2 were highly expressed in the internal stem tissues as compared to outer stem tissues and other samples. This result was confirmed with both geNorm-designated- and Norm

The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial Periarticular Bursitis in Patients with Osteoarthritis

Science.gov (United States)

Doner, Davut; Karatag, Ozan; Toprak, Canan Akgun

2017-01-01

Abstract Background This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia patella and medial meniscal tears. Patients and methods Radiological findings of 100 patients undergoing magnetic resonance imaging with a preliminary diagnosis of knee pain were retrospectively evaluated by two radiologists. The first radiologist assessed all patients in terms of osteoarthritis, chondromalacia patella and medial meniscal tear. The second radiologist was blinded to these results and assessed the presence of bursitis in all patients. Results Mild osteoarthritis (grade I and II) was determined in 55 patients and severe osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed with mild chondromalacia patella (grade I and II) and 46 with severe chondromalacia patella (grade III and IV). Medial meniscus tear was determined in 51 patients. Severe osteoarthritis and chondromalacia patella were positively correlated with meniscal tear (p chondromalacia patella (p = 0.023 and p = 0.479, respectively). Evaluation of lateral compartment bursae revealed lateral collateral ligament bursitis in 2 patients and iliotibial bursitis in 5 patients. Conclusions We observed a greater prevalence of bursitis in the medial compartment of the knee in patients with severe osteoarthritis and medial meniscus tear. PMID:29333118

The Medicago truncatula gene expression atlas web server

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Tang Yuhong

2009-12-01

Full Text Available Abstract Background Legumes (Leguminosae or Fabaceae play a major role in agriculture. Transcriptomics studies in the model legume species, Medicago truncatula, are instrumental in helping to formulate hypotheses about the role of legume genes. With the rapid growth of publically available Affymetrix GeneChip Medicago Genome Array GeneChip data from a great range of tissues, cell types, growth conditions, and stress treatments, the legume research community desires an effective bioinformatics system to aid efforts to interpret the Medicago genome through functional genomics. We developed the Medicago truncatula Gene Expression Atlas (MtGEA web server for this purpose. Description The Medicago truncatula Gene Expression Atlas (MtGEA web server is a centralized platform for analyzing the Medicago transcriptome. Currently, the web server hosts gene expression data from 156 Affymetrix GeneChip® Medicago genome arrays in 64 different experiments, covering a broad range of developmental and environmental conditions. The server enables flexible, multifaceted analyses of transcript data and provides a range of additional information about genes, including different types of annotation and links to the genome sequence, which help users formulate hypotheses about gene function. Transcript data can be accessed using Affymetrix probe identification number, DNA sequence, gene name, functional description in natural language, GO and KEGG annotation terms, and InterPro domain number. Transcripts can also be discovered through co-expression or differential expression analysis. Flexible tools to select a subset of experiments and to visualize and compare expression profiles of multiple genes have been implemented. Data can be downloaded, in part or full, in a tabular form compatible with common analytical and visualization software. The web server will be updated on a regular basis to incorporate new gene expression data and genome annotation, and is accessible

A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.

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Simone de Jong

Full Text Available Despite large-scale genome-wide association studies (GWAS, the underlying genes for schizophrenia are largely unknown. Additional approaches are therefore required to identify the genetic background of this disorder. Here we report findings from a large gene expression study in peripheral blood of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co-expression modules associated with schizophrenia. Several of these disease related modules are likely to reflect expression changes due to antipsychotic medication. However, two of the disease modules could be replicated in an independent second data set involving antipsychotic-free patients and controls. One of these robustly defined disease modules is significantly enriched with brain-expressed genes and with genetic variants that were implicated in a GWAS study, which could imply a causal role in schizophrenia etiology. The most highly connected intramodular hub gene in this module (ABCF1, is located in, and regulated by the major histocompatibility (MHC complex, which is intriguing in light of the fact that common allelic variants from the MHC region have been implicated in schizophrenia. This suggests that the MHC increases schizophrenia susceptibility via altered gene expression of regulatory genes in this network.

Clustering based gene expression feature selection method: A computational approach to enrich the classifier efficiency of differentially expressed genes

KAUST Repository

Abusamra, Heba

2016-07-20

The native nature of high dimension low sample size of gene expression data make the classification task more challenging. Therefore, feature (gene) selection become an apparent need. Selecting a meaningful and relevant genes for classifier not only decrease the computational time and cost, but also improve the classification performance. Among different approaches of feature selection methods, however most of them suffer from several problems such as lack of robustness, validation issues etc. Here, we present a new feature selection technique that takes advantage of clustering both samples and genes. Materials and methods We used leukemia gene expression dataset [1]. The effectiveness of the selected features were evaluated by four different classification methods; support vector machines, k-nearest neighbor, random forest, and linear discriminate analysis. The method evaluate the importance and relevance of each gene cluster by summing the expression level for each gene belongs to this cluster. The gene cluster consider important, if it satisfies conditions depend on thresholds and percentage otherwise eliminated. Results Initial analysis identified 7120 differentially expressed genes of leukemia (Fig. 15a), after applying our feature selection methodology we end up with specific 1117 genes discriminating two classes of leukemia (Fig. 15b). Further applying the same method with more stringent higher positive and lower negative threshold condition, number reduced to 58 genes have be tested to evaluate the effectiveness of the method (Fig. 15c). The results of the four classification methods are summarized in Table 11. Conclusions The feature selection method gave good results with minimum classification error. Our heat-map result shows distinct pattern of refines genes discriminating between two classes of leukemia.

A deep auto-encoder model for gene expression prediction.

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Xie, Rui; Wen, Jia; Quitadamo, Andrew; Cheng, Jianlin; Shi, Xinghua

2017-11-17

Gene expression is a key intermediate level that genotypes lead to a particular trait. Gene expression is affected by various factors including genotypes of genetic variants. With an aim of delineating the genetic impact on gene expression, we build a deep auto-encoder model to assess how good genetic variants will contribute to gene expression changes. This new deep learning model is a regression-based predictive model based on the MultiLayer Perceptron and Stacked Denoising Auto-encoder (MLP-SAE). The model is trained using a stacked denoising auto-encoder for feature selection and a multilayer perceptron framework for backpropagation. We further improve the model by introducing dropout to prevent overfitting and improve performance. To demonstrate the usage of this model, we apply MLP-SAE to a real genomic datasets with genotypes and gene expression profiles measured in yeast. Our results show that the MLP-SAE model with dropout outperforms other models including Lasso, Random Forests and the MLP-SAE model without dropout. Using the MLP-SAE model with dropout, we show that gene expression quantifications predicted by the model solely based on genotypes, align well with true gene expression patterns. We provide a deep auto-encoder model for predicting gene expression from SNP genotypes. This study demonstrates that deep learning is appropriate for tackling another genomic problem, i.e., building predictive models to understand genotypes' contribution to gene expression. With the emerging availability of richer genomic data, we anticipate that deep learning models play a bigger role in modeling and interpreting genomics.

Positron emission tomography imaging of gene expression

International Nuclear Information System (INIS)

Tang Ganghua

2001-01-01

The merging of molecular biology and nuclear medicine is developed into molecular nuclear medicine. Positron emission tomography (PET) of gene expression in molecular nuclear medicine has become an attractive area. Positron emission tomography imaging gene expression includes the antisense PET imaging and the reporter gene PET imaging. It is likely that the antisense PET imaging will lag behind the reporter gene PET imaging because of the numerous issues that have not yet to be resolved with this approach. The reporter gene PET imaging has wide application into animal experimental research and human applications of this approach will likely be reported soon

Understanding gene expression in coronary artery disease through ...

Indian Academy of Sciences (India)

Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes. Prathima ... Table 2. Differentially expressed genes in CAD compared to age and gender matched controls. .... Regulation of nuclear pre-mRNA domain containing 1A.

Gene expression profile of pulpitis.

Science.gov (United States)

Galicia, J C; Henson, B R; Parker, J S; Khan, A A

2016-06-01

The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

Mel-18, a mammalian Polycomb gene, regulates angiogenic gene expression of endothelial cells.

Science.gov (United States)

Jung, Ji-Hye; Choi, Hyun-Jung; Maeng, Yong-Sun; Choi, Jung-Yeon; Kim, Minhyung; Kwon, Ja-Young; Park, Yong-Won; Kim, Young-Myeong; Hwang, Daehee; Kwon, Young-Guen

2010-10-01

Mel-18 is a mammalian homolog of Polycomb group (PcG) genes. Microarray analysis revealed that Mel-18 expression was induced during endothelial progenitor cell (EPC) differentiation and correlates with the expression of EC-specific protein markers. Overexpression of Mel-18 promoted EPC differentiation and angiogenic activity of ECs. Accordingly, silencing Mel-18 inhibited EC migration and tube formation in vitro. Gene expression profiling showed that Mel-18 regulates angiogenic genes including kinase insert domain receptor (KDR), claudin 5, and angiopoietin-like 2. Our findings demonstrate, for the first time, that Mel-18 plays a significant role in the angiogenic function of ECs by regulating endothelial gene expression. Copyright © 2010 Elsevier Inc. All rights reserved.

Gene Expression Omnibus (GEO)

Data.gov (United States)

U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

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Turner Renee J

2009-08-01

Full Text Available Abstract Background Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Methods Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT, 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Results Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder. Conclusion The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

Validation of reference genes for quantifying changes in gene expression in virus-infected tobacco.

Science.gov (United States)

Baek, Eseul; Yoon, Ju-Yeon; Palukaitis, Peter

2017-10-01

To facilitate quantification of gene expression changes in virus-infected tobacco plants, eight housekeeping genes were evaluated for their stability of expression during infection by one of three systemically-infecting viruses (cucumber mosaic virus, potato virus X, potato virus Y) or a hypersensitive-response-inducing virus (tobacco mosaic virus; TMV) limited to the inoculated leaf. Five reference-gene validation programs were used to establish the order of the most stable genes for the systemically-infecting viruses as ribosomal protein L25 > β-Tubulin > Actin, and the least stable genes Ubiquitin-conjugating enzyme (UCE) genes were EF1α > Cysteine protease > Actin, and the least stable genes were GAPDH genes, three defense responsive genes were examined to compare their relative changes in gene expression caused by each virus. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression patterns in pancreatic tumors, cells and tissues.

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Anson W Lowe

2007-03-01

Full Text Available Cancers of the pancreas originate from both the endocrine and exocrine elements of the organ, and represent a major cause of cancer-related death. This study provides a comprehensive assessment of gene expression for pancreatic tumors, the normal pancreas, and nonneoplastic pancreatic disease.DNA microarrays were used to assess the gene expression for surgically derived pancreatic adenocarcinomas, islet cell tumors, and mesenchymal tumors. The addition of normal pancreata, isolated islets, isolated pancreatic ducts, and pancreatic adenocarcinoma cell lines enhanced subsequent analysis by increasing the diversity in gene expression profiles obtained. Exocrine, endocrine, and mesenchymal tumors displayed unique gene expression profiles. Similarities in gene expression support the pancreatic duct as the origin of adenocarcinomas. In addition, genes highly expressed in other cancers and associated with specific signal transduction pathways were also found in pancreatic tumors.The scope of the present work was enhanced by the inclusion of publicly available datasets that encompass a wide spectrum of human tissues and enabled the identification of candidate genes that may serve diagnostic and therapeutic goals.

MRI as an accurate tool for the diagnosis and characterization of different knee joint meniscal injuries

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Ayman F. Ahmed

2017-12-01

Conclusion: MRI of the knee will give the orthopedic surgeons ability to select suitable treatment and arthroscopic interference for their patients. MRI has high accuracy in meniscal tears diagnosis allowing accurate grading of them.

Delay in surgery predisposes to meniscal and chondral injuries in anterior cruciate ligament deficient knees

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Ravi Gupta

2016-01-01

Conclusion: Surgical delay predicts an increase in medial meniscal and lateral articular injuries justifying early rather than delayed reconstruction in ACL deficient knees. Increasing age is positively related to intraarticular injuries while females are more susceptible to lateral articular injuries.

A longitudinal study of gene expression in healthy individuals

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Tessier Michel

2009-06-01

Full Text Available Abstract Background The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22–55 years and > 55 years and gender. Methods Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR, as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays. Results Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with ~2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF, 95% of all samples profiled fell within 1.5–2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers. Conclusion This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated

Vaginal Gene Expression During Treatment With Aromatase Inhibitors.

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Kallak, Theodora Kunovac; Baumgart, Juliane; Nilsson, Kerstin; Åkerud, Helena; Poromaa, Inger Sundström; Stavreus-Evers, Anneli

2015-12-01

Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase. Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry. The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

Gene-expression profiling after exposure to C-ion beams

International Nuclear Information System (INIS)

Saegusa, Kumiko; Furuno, Aki; Ishikawa, Kenichi; Ishikawa, Atsuko; Ohtsuka, Yoshimi; Kawai, Seiko; Imai, Takashi; Nojima, Kumie

2005-01-01

It is recognized that carbon-ion beam kills cancer cells more efficiently than X-ray. In this study we have compared cellular gene expression response after carbon-ion beam exposure with that after X-ray exposure. Gene expression profiles of cultured neonatal human dermal fibroblasts (NHDF) at 0, 1, 3, 6, 12, 18, and 24 hr after exposure to 0.1, 2 and 5 Gy of X-ray or carbon-ion beam were obtained using 22K oligonucleotide microarray. N-way ANOVA analysis of whole gene expression data sets selected 960 genes for carbon-ion beam and 977 genes for X-ray, respectively. Interestingly, majority of these genes (91% for carbon-ion beam and 88% for X-ray, respectively) were down regulated. The selected genes were further classified by their dose-dependence or time-dependence of gene expression change (fold change>1.5). It was revealed that genes involved in cell proliferation had tendency to show time-dependent up regulation by carbon-ion beam. Another N-way ANOVA analysis was performed to select 510 genes, and further selection was made to find 70 genes that showed radiation species-dependent gene expression change (fold change>1.25). These genes were then categorized by the K-Mean clustering method into 4 clusters. Each cluster showed tendency to contain genes involved in cell cycle regulation, cell death, responses to stress and metabolisms, respectively. (author)

AffyMiner: mining differentially expressed genes and biological knowledge in GeneChip microarray data

Directory of Open Access Journals (Sweden)

Xia Yuannan

2006-12-01

Full Text Available Abstract Background DNA microarrays are a powerful tool for monitoring the expression of tens of thousands of genes simultaneously. With the advance of microarray technology, the challenge issue becomes how to analyze a large amount of microarray data and make biological sense of them. Affymetrix GeneChips are widely used microarrays, where a variety of statistical algorithms have been explored and used for detecting significant genes in the experiment. These methods rely solely on the quantitative data, i.e., signal intensity; however, qualitative data are also important parameters in detecting differentially expressed genes. Results AffyMiner is a tool developed for detecting differentially expressed genes in Affymetrix GeneChip microarray data and for associating gene annotation and gene ontology information with the genes detected. AffyMiner consists of the functional modules, GeneFinder for detecting significant genes in a treatment versus control experiment and GOTree for mapping genes of interest onto the Gene Ontology (GO space; and interfaces to run Cluster, a program for clustering analysis, and GenMAPP, a program for pathway analysis. AffyMiner has been used for analyzing the GeneChip data and the results were presented in several publications. Conclusion AffyMiner fills an important gap in finding differentially expressed genes in Affymetrix GeneChip microarray data. AffyMiner effectively deals with multiple replicates in the experiment and takes into account both quantitative and qualitative data in identifying significant genes. AffyMiner reduces the time and effort needed to compare data from multiple arrays and to interpret the possible biological implications associated with significant changes in a gene's expression.

Microarray gene expression profiling and analysis in renal cell carcinoma

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Sadhukhan Provash

2004-06-01

Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

The use of MRI in the investigation of lateral meniscal tear post medial unicompartmental knee replacement

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Sanil H. Ajwani, MBChB, BSc (Hons, MRCS

2015-06-01

Full Text Available The evaluation of lateral knee pain in patients with a medial unicompartmental knee replacement (UKR is complex. The native lateral compartment structures are prone to the same injuries as patients with normal knees. Historical reports of lateral meniscal injury post medial UKR have argued MRI evaluation is obsolete due to artefact caused by the prosthesis. We report a case of lateral meniscal injury in a patient two years after successful medial UKR. We identified the offending pathology via utilization of MRI scanners adopting metal artefact reduction sequences (MARS. The MARS MRI protocol helps clinicians accurately and non-invasively evaluate soft tissue structures in knees with metal prostheses. It also allows surgeons to accurately counsel patients and provides a higher degree of certainty in treating the pathology.

Regulation of Gene Expression in Protozoa Parasites

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Consuelo Gomez

2010-01-01

Full Text Available Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.

Regulation of gene expression in protozoa parasites.

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Gomez, Consuelo; Esther Ramirez, M; Calixto-Galvez, Mercedes; Medel, Olivia; Rodríguez, Mario A

2010-01-01

Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.

A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes

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de Jong, Simone; Boks, Marco P M; Fuller, Tova F

2012-01-01

Despite large-scale genome-wide association studies (GWAS), the underlying genes for schizophrenia are largely unknown. Additional approaches are therefore required to identify the genetic background of this disorder. Here we report findings from a large gene expression study in peripheral blood...... of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co......, and regulated by the major histocompatibility (MHC) complex, which is intriguing in light of the fact that common allelic variants from the MHC region have been implicated in schizophrenia. This suggests that the MHC increases schizophrenia susceptibility via altered gene expression of regulatory genes...

Divergent and nonuniform gene expression patterns in mouse brain

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Morris, John A.; Royall, Joshua J.; Bertagnolli, Darren; Boe, Andrew F.; Burnell, Josh J.; Byrnes, Emi J.; Copeland, Cathy; Desta, Tsega; Fischer, Shanna R.; Goldy, Jeff; Glattfelder, Katie J.; Kidney, Jolene M.; Lemon, Tracy; Orta, Geralyn J.; Parry, Sheana E.; Pathak, Sayan D.; Pearson, Owen C.; Reding, Melissa; Shapouri, Sheila; Smith, Kimberly A.; Soden, Chad; Solan, Beth M.; Weller, John; Takahashi, Joseph S.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hohmann, John G.; Jones, Allan R.

2010-01-01

Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs. PMID:20956311

Rethinking cell-cycle-dependent gene expression in Schizosaccharomyces pombe.

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Cooper, Stephen

2017-11-01

Three studies of gene expression during the division cycle of Schizosaccharomyces pombe led to the proposal that a large number of genes are expressed at particular times during the S. pombe cell cycle. Yet only a small fraction of genes proposed to be expressed in a cell-cycle-dependent manner are reproducible in all three published studies. In addition to reproducibility problems, questions about expression amplitudes, cell-cycle timing of expression, synchronization artifacts, and the problem with methods for synchronizing cells must be considered. These problems and complications prompt the idea that caution should be used before accepting the conclusion that there are a large number of genes expressed in a cell-cycle-dependent manner in S. pombe.

Variation-preserving normalization unveils blind spots in gene expression profiling

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Roca, Carlos P.; Gomes, Susana I. L.; Amorim, Mónica J. B.; Scott-Fordsmand, Janeck J.

2017-01-01

RNA-Seq and gene expression microarrays provide comprehensive profiles of gene activity, but lack of reproducibility has hindered their application. A key challenge in the data analysis is the normalization of gene expression levels, which is currently performed following the implicit assumption that most genes are not differentially expressed. Here, we present a mathematical approach to normalization that makes no assumption of this sort. We have found that variation in gene expression is much larger than currently believed, and that it can be measured with available assays. Our results also explain, at least partially, the reproducibility problems encountered in transcriptomics studies. We expect that this improvement in detection will help efforts to realize the full potential of gene expression profiling, especially in analyses of cellular processes involving complex modulations of gene expression. PMID:28276435

G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes

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Lemay Danielle G

2012-09-01

Full Text Available Abstract Background In previous studies, gene neighborhoods—spatial clusters of co-expressed genes in the genome—have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously. Results Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods. Conclusions Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

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Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

2017-11-13

The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly

G-NEST: A gene neighborhood scoring tool to identify co-conserved, co-expressed genes

Science.gov (United States)

In previous studies, gene neighborhoods--spatial clusters of co-expressed genes in the genome--have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Sc...

Selection for the compactness of highly expressed genes in Gallus gallus

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Zhou Ming

2010-05-01

Full Text Available Abstract Background Coding sequence (CDS length, gene size, and intron length vary within a genome and among genomes. Previous studies in diverse organisms, including human, D. Melanogaster, C. elegans, S. cerevisiae, and Arabidopsis thaliana, indicated that there are negative relationships between expression level and gene size, CDS length as well as intron length. Different models such as selection for economy model, genomic design model, and mutational bias hypotheses have been proposed to explain such observation. The debate of which model is a superior one to explain the observation has not been settled down. The chicken (Gallus gallus is an important model organism that bridges the evolutionary gap between mammals and other vertebrates. As D. Melanogaster, chicken has a larger effective population size, selection for chicken genome is expected to be more effective in increasing protein synthesis efficiency. Therefore, in this study the chicken was used as a model organism to elucidate the interaction between gene features and expression pattern upon selection pressure. Results Based on different technologies, we gathered expression data for nuclear protein coding, single-splicing genes from Gallus gallus genome and compared them with gene parameters. We found that gene size, CDS length, first intron length, average intron length, and total intron length are negatively correlated with expression level and expression breadth significantly. The tissue specificity is positively correlated with the first intron length but negatively correlated with the average intron length, and not correlated with the CDS length and protein domain numbers. Comparison analyses showed that ubiquitously expressed genes and narrowly expressed genes with the similar expression levels do not differ in compactness. Our data provided evidence that the genomic design model can not, at least in part, explain our observations. We grouped all somatic-tissue-specific genes

Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

KAUST Repository

Othoum, Ghofran K

2013-05-01

Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

KAUST Repository

Othoum, Ghofran K

2013-01-01

Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

Aging and Gene Expression in the Primate Brain

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Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

2005-02-18

It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

Aging and gene expression in the primate brain.

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Hunter B Fraser

2005-09-01

Full Text Available It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

Clock Genes Influence Gene Expression in Growth Plate and Endochondral Ossification in Mice*

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Takarada, Takeshi; Kodama, Ayumi; Hotta, Shogo; Mieda, Michihiro; Shimba, Shigeki; Hinoi, Eiichi; Yoneda, Yukio

2012-01-01

We have previously shown transient promotion by parathyroid hormone of Period-1 (Per1) expression in cultured chondrocytes. Here we show the modulation by clock genes of chondrogenic differentiation through gene transactivation of the master regulator of chondrogenesis Indian hedgehog (IHH) in chondrocytes of the growth plate. Several clock genes were expressed with oscillatory rhythmicity in cultured chondrocytes and rib growth plate in mice, whereas chondrogenesis was markedly inhibited in stable transfectants of Per1 in chondrocytic ATDC5 cells and in rib growth plate chondrocytes from mice deficient of brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1). Ihh promoter activity was regulated by different clock gene products, with clear circadian rhythmicity in expression profiles of Ihh in the growth plate. In BMAL1-null mice, a predominant decrease was seen in Ihh expression in the growth plate with a smaller body size than in wild-type mice. BMAL1 deficit led to disruption of the rhythmic expression profiles of both Per1 and Ihh in the growth plate. A clear rhythmicity was seen with Ihh expression in ATDC5 cells exposed to dexamethasone. In young mice defective of BMAL1 exclusively in chondrocytes, similar abnormalities were found in bone growth and Ihh expression. These results suggest that endochondral ossification is under the regulation of particular clock gene products expressed in chondrocytes during postnatal skeletogenesis through a mechanism relevant to the rhythmic Ihh expression. PMID:22936800

A Gene Expression Classifier of Node-Positive Colorectal Cancer

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Paul F. Meeh

2009-10-01

Full Text Available We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10-6. We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor. We analyzed the expression levels of these 12 upregulated genes in a validation panel of 23 additional tumors and developed an optimized seven-gene logistic regression classifier. The classifier discriminated between node-negative and node-positive tumors with 86% sensitivity and 80% specificity. Receiver operating characteristic analysis of the classifier revealed an area under the curve of 0.86. Experimental manipulation of the function of one classification gene, Fibronectin, caused profound effects on invasion and migration of colorectal cancer cells in vitro. These results suggest that the development of node-positive colorectal cancer occurs in part through elevated epithelial FN1 expression and suggest novel strategies for the diagnosis and treatment of advanced disease.

Morphologic characterization of meniscal root ligaments in the human knee with magnetic resonance microscopy at 11.7 and 3 T

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Chang, Eric Y.; Chung, Christine B. [VA San Diego Healthcare System, Department of Radiology, San Diego, CA (United States); University of California, San Diego Medical Center, Department of Radiology, San Diego, CA (United States); Biswas, Reni; DiCamillo, Paul; Statum, Sheronda; Tafur, Monica; Bydder, Graeme M. [University of California, San Diego Medical Center, Department of Radiology, San Diego, CA (United States)

2014-10-15

To determine the feasibility of using MR microscopy to characterize the root ligaments of the human knee at both ultra-high-field (11.7 T) and high-field (3 T) strengths. Seven fresh cadaveric knees were used for this study. Six specimens were imaged at 11.7 T and one specimen at 3 T using isotropic or near-isotropic voxels. Histologic correlation was performed on the posteromedial root ligament of one specimen. Meniscal root ligament shape, signal intensity, and ultrastructure were characterized. High-resolution, high-contrast volumetric images were generated from both MR systems. Meniscal root ligaments were predominantly oval in shape. Increased signal intensity was most evident at the posteromedial and posterolateral root ligaments. On the specimen that underwent histologic preparation, increased signal intensity corresponded to regions of enthesis fibrocartilage. Collagen fascicles were continuous between the menisci and root ligaments. Predominantly horizontal meniscal radial tie fibers continued into the root ligaments as vertical endoligaments. MR microscopy can be used to characterize and delineate the distinct ultrastructure of the root ligaments on both ultra-high-field- and high-field-strength MR systems. (orig.)

The relationship between chondromalacia patella, medial meniscal tear and medial periarticular bursitis in patients with osteoarthritis

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Resorlu Mustafa

2017-11-01

Full Text Available This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa in osteoarthritis, chondromalacia patella and medial meniscal tears.

Rhythmic diel pattern of gene expression in juvenile maize leaf.

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Maciej Jończyk

Full Text Available BACKGROUND: Numerous biochemical and physiological parameters of living organisms follow a circadian rhythm. Although such rhythmic behavior is particularly pronounced in plants, which are strictly dependent on the daily photoperiod, data on the molecular aspects of the diurnal cycle in plants is scarce and mostly concerns the model species Arabidopsis thaliana. Here we studied the leaf transcriptome in seedlings of maize, an important C4 crop only distantly related to A. thaliana, throughout a cycle of 10 h darkness and 14 h light to look for rhythmic patterns of gene expression. RESULTS: Using DNA microarrays comprising ca. 43,000 maize-specific probes we found that ca. 12% of all genes showed clear-cut diel rhythms of expression. Cluster analysis identified 35 groups containing from four to ca. 1,000 genes, each comprising genes of similar expression patterns. Perhaps unexpectedly, the most pronounced and most common (concerning the highest number of genes expression maxima were observed towards and during the dark phase. Using Gene Ontology classification several meaningful functional associations were found among genes showing similar diel expression patterns, including massive induction of expression of genes related to gene expression, translation, protein modification and folding at dusk and night. Additionally, we found a clear-cut tendency among genes belonging to individual clusters to share defined transcription factor-binding sequences. CONCLUSIONS: Co-expressed genes belonging to individual clusters are likely to be regulated by common mechanisms. The nocturnal phase of the diurnal cycle involves gross induction of fundamental biochemical processes and should be studied more thoroughly than was appreciated in most earlier physiological studies. Although some general mechanisms responsible for the diel regulation of gene expression might be shared among plants, details of the diurnal regulation of gene expression seem to differ

Molecular transformation, gene cloning, and gene expression systems for filamentous fungi

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Gold, Scott E.; Duick, John W.; Redman, Regina S.; Rodriguez, Rusty J.

2001-01-01

This chapter discusses the molecular transformation, gene cloning, and gene expression systems for filamentous fungi. Molecular transformation involves the movement of discrete amounts of DNA into cells, the expression of genes on the transported DNA, and the sustainable replication of the transforming DNA. The ability to transform fungi is dependent on the stable replication and expression of genes located on the transforming DNA. Three phenomena observed in bacteria, that is, competence, plasmids, and restriction enzymes to facilitate cloning, were responsible for the development of molecular transformation in fungi. Initial transformation success with filamentous fungi, involving the complementation of auxotrophic mutants by exposure to sheared genomic DNA or RNA from wt isolates, occurred with low transformation efficiencies. In addition, it was difficult to retrieve complementing DNA fragments and isolate genes of interest. This prompted the development of transformation vectors and methods to increase efficiencies. The physiological studies performed with fungi indicated that the cell wall could be removed to generate protoplasts. It was evident that protoplasts could be transformed with significantly greater efficiencies than walled cells.

With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies.

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Chapman, Joanne R; Waldenström, Jonas

2015-01-01

The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with β-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.

Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

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Lun Yang

Full Text Available Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

Gravity-regulated gene expression in Arabidopsis thaliana

Science.gov (United States)

Sederoff, Heike; Brown, Christopher S.; Heber, Steffen; Kajla, Jyoti D.; Kumar, Sandeep; Lomax, Terri L.; Wheeler, Benjamin; Yalamanchili, Roopa

Plant growth and development is regulated by changes in environmental signals. Plants sense environmental changes and respond to them by modifying gene expression programs to ad-just cell growth, differentiation, and metabolism. Functional expression of genes comprises many different processes including transcription, translation, post-transcriptional and post-translational modifications, as well as the degradation of RNA and proteins. Recently, it was discovered that small RNAs (sRNA, 18-24 nucleotides long), which are heritable and systemic, are key elements in regulating gene expression in response to biotic and abiotic changes. Sev-eral different classes of sRNAs have been identified that are part of a non-cell autonomous and phloem-mobile network of regulators affecting transcript stability, translational kinetics, and DNA methylation patterns responsible for heritable transcriptional silencing (epigenetics). Our research has focused on gene expression changes in response to gravistimulation of Arabidopsis roots. Using high-throughput technologies including microarrays and 454 sequencing, we iden-tified rapid changes in transcript abundance of genes as well as differential expression of small RNA in Arabidopsis root apices after minutes of reorientation. Some of the differentially regu-lated transcripts are encoded by genes that are important for the bending response. Functional mutants of those genes respond faster to reorientation than the respective wild type plants, indicating that these proteins are repressors of differential cell elongation. We compared the gravity responsive sRNAs to the changes in transcript abundances of their putative targets and identified several potential miRNA: target pairs. Currently, we are using mutant and transgenic Arabidopsis plants to characterize the function of those miRNAs and their putative targets in gravitropic and phototropic responses in Arabidopsis.

Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

Directory of Open Access Journals (Sweden)

Marta Miró-Murillo

Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

Hepatocyte specific expression of human cloned genes

Energy Technology Data Exchange (ETDEWEB)

Cortese, R

1986-01-01

A large number of proteins are specifically synthesized in the hepatocyte. Only the adult liver expresses the complete repertoire of functions which are required at various stages during development. There is therefore a complex series of regulatory mechanisms responsible for the maintenance of the differentiated state and for the developmental and physiological variations in the pattern of gene expression. Human hepatoma cell lines HepG2 and Hep3B display a pattern of gene expression similar to adult and fetal liver, respectively; in contrast, cultured fibroblasts or HeLa cells do not express most of the liver specific genes. They have used these cell lines for transfection experiments with cloned human liver specific genes. DNA segments coding for alpha1-antitrypsin and retinol binding protein (two proteins synthesized both in fetal and adult liver) are expressed in the hepatoma cell lines HepG2 and Hep3B, but not in HeLa cells or fibroblasts. A DNA segment coding for haptoglobin (a protein synthesized only after birth) is only expressed in the hepatoma cell line HepG2 but not in Hep3B nor in non hepatic cell lines. The information for tissue specific expression is located in the 5' flanking region of all three genes. In vivo competition experiments show that these DNA segments bind to a common, apparently limiting, transacting factor. Conventional techniques (Bal deletions, site directed mutagenesis, etc.) have been used to precisely identify the DNA sequences responsible for these effects. The emerging picture is complex: they have identified multiple, separate transcriptional signals, essential for maximal promoter activation and tissue specific expression. Some of these signals show a negative effect on transcription in fibroblast cell lines.

Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis

Science.gov (United States)

dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

2015-01-01

Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

Vascular Gene Expression in Nonneoplastic and Malignant Brain

Science.gov (United States)

Madden, Stephen L.; Cook, Brian P.; Nacht, Mariana; Weber, William D.; Callahan, Michelle R.; Jiang, Yide; Dufault, Michael R.; Zhang, Xiaoming; Zhang, Wen; Walter-Yohrling, Jennifer; Rouleau, Cecile; Akmaev, Viatcheslav R.; Wang, Clarence J.; Cao, Xiaohong; St. Martin, Thia B.; Roberts, Bruce L.; Teicher, Beverly A.; Klinger, Katherine W.; Stan, Radu-Virgil; Lucey, Brenden; Carson-Walter, Eleanor B.; Laterra, John; Walter, Kevin A.

2004-01-01

Malignant gliomas are uniformly lethal tumors whose morbidity is mediated in large part by the angiogenic response of the brain to the invading tumor. This profound angiogenic response leads to aggressive tumor invasion and destruction of surrounding brain tissue as well as blood-brain barrier breakdown and life-threatening cerebral edema. To investigate the molecular mechanisms governing the proliferation of abnormal microvasculature in malignant brain tumor patients, we have undertaken a cell-specific transcriptome analysis from surgically harvested nonneoplastic and tumor-associated endothelial cells. SAGE-derived endothelial cell gene expression patterns from glioma and nonneoplastic brain tissue reveal distinct gene expression patterns and consistent up-regulation of certain glioma endothelial marker genes across patient samples. We define the G-protein-coupled receptor RDC1 as a tumor endothelial marker whose expression is distinctly induced in tumor endothelial cells of both brain and peripheral vasculature. Further, we demonstrate that the glioma-induced gene, PV1, shows expression both restricted to endothelial cells and coincident with endothelial cell tube formation. As PV1 provides a framework for endothelial cell caveolar diaphragms, this protein may serve to enhance glioma-induced disruption of the blood-brain barrier and transendothelial exchange. Additional characterization of this extensive brain endothelial cell gene expression database will provide unique molecular insights into vascular gene expression. PMID:15277233

GeneCAT--novel webtools that combine BLAST and co-expression analyses

DEFF Research Database (Denmark)

Mutwil, Marek; Obro, Jens; Willats, William G T

2008-01-01

The gene co-expression analysis toolbox (GeneCAT) introduces several novel microarray data analyzing tools. First, the multigene co-expression analysis, combined with co-expressed gene networks, provides a more powerful data mining technique than standard, single-gene co-expression analysis. Second...... orthologs in the plant model organisms Arabidopsis thaliana and Hordeum vulgare (Barley). GeneCAT is equipped with expression data for the model plant A. thaliana, and first to introduce co-expression mining tools for the monocot Barley. GeneCAT is available at http://genecat.mpg.de....

Automated discovery of functional generality of human gene expression programs.

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Georg K Gerber

2007-08-01

Full Text Available An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-kappaB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal

Blood cell gene expression profiling in rheumatoid arthritis. Discriminative genes and effect of rheumatoid factor

DEFF Research Database (Denmark)

Bovin, Lone Frier; Rieneck, Klaus; Workman, Christopher

2004-01-01

To study the pathogenic importance of the rheumatoid factor (RF) in rheumatoid arthritis (RA) and to identify genes differentially expressed in patients and healthy individuals, total RNA was isolated from peripheral blood mononuclear cells (PBMC) from eight RF-positive and six RF-negative RA...... patients, and seven healthy controls. Gene expression of about 10,000 genes were examined using oligonucleotide-based DNA chip microarrays. The analyses showed no significant differences in PBMC expression patterns from RF-positive and RF-negative patients. However, comparisons of gene expression patterns...

A compendium of canine normal tissue gene expression.

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Joseph Briggs

Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

Expression of streptavidin gene in bacteria and plants

International Nuclear Information System (INIS)

Guan, Xueni; Wurtele, E.S.; Nikolau, B.J.

1990-01-01

Six biotin-containing proteins are present in plants, representing at least four different biotin enzymes. The physiological function of these biotin enzymes is not understood. Streptavidin, a protein from Streptomyces avidinii, binds tightly and specifically to biotin causing inactivation of biotin enzymes. One approach to elucidating the physiological function of biotin enzymes in plant metabolism is to create transgenic plants expressing the streptavidin gene. A plasmid containing a fused streptavidin-beta-galactosidase gene has been expressed in E. coli. We also have constructed various fusion genes that include an altered CaMV 35S promoter, signal peptides to target the streptavidin protein to specific organelles, and the streptavidin coding gene. We are examining the expression of these genes in cells of carrot

Evaluation of suitable reference genes for gene expression studies ...

Indian Academy of Sciences (India)

2011-12-14

Dec 14, 2011 ... MADS family of TFs control floral organ identity within each whorl of the flower by activating downstream genes. Measuring gene expression in different tissue types and developmental stages is of fundamental importance in TFs functional research. In last few years, quantitative real-time. PCR (qRT-PCR) ...

Identification of differentially expressed genes in cucumber (Cucumis sativus L.) root under waterlogging stress by digital gene expression profile.

Science.gov (United States)

Qi, Xiao-Hua; Xu, Xue-Wen; Lin, Xiao-Jian; Zhang, Wen-Jie; Chen, Xue-Hao

2012-03-01

High-throughput tag-sequencing (Tag-seq) analysis based on the Solexa Genome Analyzer platform was applied to analyze the gene expression profiling of cucumber plant at 5 time points over a 24h period of waterlogging treatment. Approximately 5.8 million total clean sequence tags per library were obtained with 143013 distinct clean tag sequences. Approximately 23.69%-29.61% of the distinct clean tags were mapped unambiguously to the unigene database, and 53.78%-60.66% of the distinct clean tags were mapped to the cucumber genome database. Analysis of the differentially expressed genes revealed that most of the genes were down-regulated in the waterlogging stages, and the differentially expressed genes mainly linked to carbon metabolism, photosynthesis, reactive oxygen species generation/scavenging, and hormone synthesis/signaling. Finally, quantitative real-time polymerase chain reaction using nine genes independently verified the tag-mapped results. This present study reveals the comprehensive mechanisms of waterlogging-responsive transcription in cucumber. Copyright © 2011 Elsevier Inc. All rights reserved.

Three-Dimensional Coculture of Meniscal Cells and Mesenchymal Stem Cells in Collagen Type I Hydrogel on a Small Intestinal Matrix-A Pilot Study Toward Equine Meniscus Tissue Engineering.

Science.gov (United States)

Kremer, Antje; Ribitsch, Iris; Reboredo, Jenny; Dürr, Julia; Egerbacher, Monika; Jenner, Florien; Walles, Heike

2017-05-01

Meniscal injuries are the most frequently encountered soft tissue injuries in the equine stifle joint. Due to the inherent limited repair potential of meniscal tissue, meniscal injuries do not only affect the meniscus itself but also lead to impaired joint homeostasis and secondary osteoarthritis. The presented study compares 3D coculture constructs of primary equine mesenchymal stem cells (MSC) and meniscus cells (MC) seeded on three different scaffolds-a cell-laden collagen type I hydrogel (Col I gel), a tissue-derived small intestinal matrix scaffold (SIS-muc) and a combination thereof-for their qualification to be applied for meniscus tissue engineering. To investigate cell attachment of primary MC and MSC on SIS-muc matrix SEM pictures were performed. For molecular analysis, lyophilized samples of coculture constructs with different cell ratios (100% MC, 100% MSC, and 50% MC and 50% MSC, 20% MC, and 80% MSC) were digested and analyzed for DNA and GAG content. Active matrix remodeling of 3D coculture models was indicated by matrix metalloproteinases detection. For comparison of tissue-engineered constructs with the histologic architecture of natural equine menisci, paired lateral and medial menisci of 15 horses representing different age groups were examined. A meniscus phenotype with promising similarity to native meniscus tissue in its GAG/DNA expression in addition to Col I, Col II, and Aggrecan production was achieved using a scaffold composed of Col I gel on SIS-muc combined with a coculture of MC and MSC. The results encourage further development of this scaffold-cell combination for meniscus tissue engineering.

Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression

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Cohn Zachary A

2007-06-01

Full Text Available Abstract Background Cartilage plays a fundamental role in the development of the human skeleton. Early in embryogenesis, mesenchymal cells condense and differentiate into chondrocytes to shape the early skeleton. Subsequently, the cartilage anlagen differentiate to form the growth plates, which are responsible for linear bone growth, and the articular chondrocytes, which facilitate joint function. However, despite the multiplicity of roles of cartilage during human fetal life, surprisingly little is known about its transcriptome. To address this, a whole genome microarray expression profile was generated using RNA isolated from 18–22 week human distal femur fetal cartilage and compared with a database of control normal human tissues aggregated at UCLA, termed Celsius. Results 161 cartilage-selective genes were identified, defined as genes significantly expressed in cartilage with low expression and little variation across a panel of 34 non-cartilage tissues. Among these 161 genes were cartilage-specific genes such as cartilage collagen genes and 25 genes which have been associated with skeletal phenotypes in humans and/or mice. Many of the other cartilage-selective genes do not have established roles in cartilage or are novel, unannotated genes. Quantitative RT-PCR confirmed the unique pattern of gene expression observed by microarray analysis. Conclusion Defining the gene expression pattern for cartilage has identified new genes that may contribute to human skeletogenesis as well as provided further candidate genes for skeletal dysplasias. The data suggest that fetal cartilage is a complex and transcriptionally active tissue and demonstrate that the set of genes selectively expressed in the tissue has been greatly underestimated.

The contribution of 3D quantitative meniscal and cartilage measures to variation in normal radiographic joint space width—Data from the Osteoarthritis Initiative healthy reference cohort

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Roth, Melanie, E-mail: melanie.roth@pmu.ac.at [Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg (Austria); Wirth, Wolfgang, E-mail: wolfgang.wirth@pmu.ac.at [Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg (Austria); Chondrometrics GmbH, Ulrichshöglerstrasse 23, 83404, Ainring (Germany); Emmanuel, Katja, E-mail: katja.emmanuel@icloud.com [Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg (Austria); Department of Orthopedics and Traumatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020, Salzburg (Austria); Culvenor, Adam G., E-mail: adam.culvenor@pmu.ac.at [Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg (Austria); School of Allied Health, La Trobe University, Plenty Road, Bundoora, 3086, Victoria (Australia); Eckstein, Felix, E-mail: felix.eckstein@pmu.ac.at [Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg (Austria); Chondrometrics GmbH, Ulrichshöglerstrasse 23, 83404, Ainring (Germany)

2017-02-15

Objective: To explore to what extent three-dimensional measures of the meniscus and femorotibial cartilage explain the variation in medial and lateral femorotibial radiographic joint space width (JSW), in healthy men and women. Methods: The right knees of 87 Osteoarthritis Initiative healthy reference participants (no symptoms, radiographic signs or risk factors of osteoarthritis; 37 men, 50 women; age 55.0 ± 7.6; BMI 24.4 ± 3.1) were assessed. Quantitative measures of subregional femorotibial cartilage thickness and meniscal position and morphology were computed from segmented magnetic resonance images. Minimal and medial/lateral fixed-location JSW were determined from fixed-flexion radiographs. Correlation and regression analyses were used to explore the contribution of demographic, cartilage and meniscal parameters to JSW in healthy subjects. Results: The correlation with (medial) minimal JSW was somewhat stronger for cartilage thickness (0.54 ≤ r ≤ 0.67) than for meniscal (−0.31 ≤ r ≤ 0.50) or demographic measures (−0.15 ≤ r ≤ 0.48), in particular in men. In women, in contrast, the strength of the correlations of cartilage thickness and meniscal measures with minimal JSW were in the same range. Fixed-location JSW measures showed stronger correlations with cartilage thickness (r ≥ 0.68 medially; r ≥ 0.59 laterally) than with meniscal measures (r ≤ |0.32| medially; r ≤ |0.32| laterally). Stepwise regression models revealed that meniscal measures added significant independent information to the total variance explained in minimal JSW (adjusted multiple r{sup 2} = 58%) but not in medial or lateral fixed-location JSW (r{sup 2} = 60/51%, respectively). Conclusions: In healthy subjects, minimal JSW was observed to reflect a combination of cartilage and meniscal measures, particularly in women. Fixed-location JSW, in contrast, was found to be dominated by variance in cartilage thickness in both men and women, with somewhat higher correlations

Gene expression profiling of resting and activated vascular smooth muscle cells by serial analysis of gene expression and clustering analysis

NARCIS (Netherlands)

Beauchamp, Nicholas J.; van Achterberg, Tanja A. E.; Engelse, Marten A.; Pannekoek, Hans; de Vries, Carlie J. M.

2003-01-01

Migration and proliferation of vascular smooth muscle cells (SMCs) are key events in atherosclerosis. However, little is known about alterations in gene expression upon transition of the quiescent, contractile SMC to the proliferative SMC. We performed serial analysis of gene expression (SAGE) of

Oxygen and tissue culture affect placental gene expression.

Science.gov (United States)

Brew, O; Sullivan, M H F

2017-07-01

Placental explant culture is an important model for studying placental development and functions. We investigated the differences in placental gene expression in response to tissue culture, atmospheric and physiologic oxygen concentrations. Placental explants were collected from normal term (38-39 weeks of gestation) placentae with no previous uterine contractile activity. Placental transcriptomic expressions were evaluated with GeneChip ® Human Genome U133 Plus 2.0 arrays (Affymetrix). We uncovered sub-sets of genes that regulate response to stress, induction of apoptosis programmed cell death, mis-regulation of cell growth, proliferation, cell morphogenesis, tissue viability, and protection from apoptosis in cultured placental explants. We also identified a sub-set of genes with highly unstable pattern of expression after exposure to tissue culture. Tissue culture irrespective of oxygen concentration induced dichotomous increase in significant gene expression and increased enrichment of significant pathways and transcription factor targets (TFTs) including HIF1A. The effect was exacerbated by culture at atmospheric oxygen concentration, where further up-regulation of TFTs including PPARA, CEBPD, HOXA9 and down-regulated TFTs such as JUND/FOS suggest intrinsic heightened key biological and metabolic mechanisms such as glucose use, lipid biosynthesis, protein metabolism; apoptosis, inflammatory responses; and diminished trophoblast proliferation, differentiation, invasion, regeneration, and viability. These findings demonstrate that gene expression patterns differ between pre-culture and cultured explants, and the gene expression of explants cultured at atmospheric oxygen concentration favours stressed, pro-inflammatory and increased apoptotic transcriptomic response. Copyright © 2017 Elsevier Ltd. All rights reserved.

VH gene expression and regulation in the mutant Alicia rabbit. Rescue of VHa2 allotype expression.

Science.gov (United States)

Chen, H T; Alexander, C B; Young-Cooper, G O; Mage, R G

1993-04-01

Rabbits of the Alicia strain, derived from rabbits expressing the VHa2 allotype, have a mutation in the H chain locus that has a cis effect upon the expression of VHa2 and VHa- genes. A small deletion at the most J-proximal (3') end of the VH locus leads to low expression of all the genes on the entire chromosome in heterozygous ali mutants and altered relative expression of VH genes in homozygotes. To study VH gene expression and regulation, we used the polymerase chain reaction to amplify the VH genes expressed in spleens of young and adult wild-type and mutant Alicia rabbits. The cDNA from reverse transcription of splenic mRNA was amplified and polymerase chain reaction libraries were constructed and screened with oligonucleotides from framework regions 1 and 3, as well as JH. Thirty-three VH-positive clones were sequenced and analyzed. We found that in mutant Alicia rabbits, products of the first functional VH gene (VH4a2), (or VH4a2-like genes) were expressed in 2- to 8-wk-olds. Expression of both the VHx and VHy types of VHa- genes was also elevated but the relative proportions of VHx and VHy, especially VHx, decreased whereas the relative levels of expression of VH4a2 or VH4a2-like genes increased with age. Our results suggest that the appearance of sequences resembling that of the VH1a2, which is deleted in the mutant ali rabbits, could be caused by alterations of the sequences of the rearranged VH4a2 genes by gene conversions and/or rearrangement of upstream VH1a2-like genes later in development.

The human cumulus--oocyte complex gene-expression profile

Science.gov (United States)

Assou, Said; Anahory, Tal; Pantesco, Véronique; Le Carrour, Tanguy; Pellestor, Franck; Klein, Bernard; Reyftmann, Lionel; Dechaud, Hervé; De Vos, John; Hamamah, Samir

2006-01-01

BACKGROUND The understanding of the mechanisms regulating human oocyte maturation is still rudimentary. We have identified transcripts differentially expressed between immature and mature oocytes, and cumulus cells. METHODS Using oligonucleotides microarrays, genome wide gene expression was studied in pooled immature and mature oocytes or cumulus cells from patients who underwent IVF. RESULTS In addition to known genes such as DAZL, BMP15 or GDF9, oocytes upregulated 1514 genes. We show that PTTG3 and AURKC are respectively the securin and the Aurora kinase preferentially expressed during oocyte meiosis. Strikingly, oocytes overexpressed previously unreported growth factors such as TNFSF13/APRIL, FGF9, FGF14, and IL4, and transcription factors including OTX2, SOX15 and SOX30. Conversely, cumulus cells, in addition to known genes such as LHCGR or BMPR2, overexpressed cell-tocell signaling genes including TNFSF11/RANKL, numerous complement components, semaphorins (SEMA3A, SEMA6A, SEMA6D) and CD genes such as CD200. We also identified 52 genes progressively increasing during oocyte maturation, comprising CDC25A and SOCS7. CONCLUSION The identification of genes up and down regulated during oocyte maturation greatly improves our understanding of oocyte biology and will provide new markers that signal viable and competent oocytes. Furthermore, genes found expressed in cumulus cells are potential markers of granulosa cell tumors. PMID:16571642

Platelet-derived growth factor (PDGF) B-chain gene expression by activated blood monocytes precedes the expression of the PDGF A-chain gene

International Nuclear Information System (INIS)

Martinet, Y.; Jaffe, H.A.; Yamauchi, K.; Betsholtz, C.; Westermark, B.; Heldin, C.H.; Crystal, R.G.

1987-01-01

When activated, normal human blood monocytes are known to express the c-sis proto-oncogene coding for PDGF B-chain. Since normal human platelet PDGF molecules are dimers of A and B chains and platelets and monocytes are derived from the same marrow precursors, activated blood monocytes were simultaneously evaluated for their expression of PDGF A and B chain genes. Human blood monocytes were purified by adherence, cultured with or without activation by lipopolysaccharide and poly(A)+ RNA evaluated using Northern analysis and 32 P-labeled A-chain and B-chain (human c-sis) probes. Unstimulated blood monocytes did not express either A-chain or B-chain genes. In contrast, activated monocytes expressed a 4.2 kb mRNA B-chain transcript at 4 hr, but the B-chain mRNA levels declined significantly over the next 18 hr. In comparison, activated monocytes expressed very little A-chain mRNA at 4 hr, but at 12 hr 1.9, 2.3, and 2.8 kb transcripts were observed and persisted through 24 hr. Thus, activation of blood monocytes is followed by PDGF B-chain gene expression preceding PDGF A-chain gene expression, suggesting a difference in the regulation of the expression of the genes for these two chains by these cells

Finding gene regulatory network candidates using the gene expression knowledge base.

Science.gov (United States)

Venkatesan, Aravind; Tripathi, Sushil; Sanz de Galdeano, Alejandro; Blondé, Ward; Lægreid, Astrid; Mironov, Vladimir; Kuiper, Martin

2014-12-10

Network-based approaches for the analysis of large-scale genomics data have become well established. Biological networks provide a knowledge scaffold against which the patterns and dynamics of 'omics' data can be interpreted. The background information required for the construction of such networks is often dispersed across a multitude of knowledge bases in a variety of formats. The seamless integration of this information is one of the main challenges in bioinformatics. The Semantic Web offers powerful technologies for the assembly of integrated knowledge bases that are computationally comprehensible, thereby providing a potentially powerful resource for constructing biological networks and network-based analysis. We have developed the Gene eXpression Knowledge Base (GeXKB), a semantic web technology based resource that contains integrated knowledge about gene expression regulation. To affirm the utility of GeXKB we demonstrate how this resource can be exploited for the identification of candidate regulatory network proteins. We present four use cases that were designed from a biological perspective in order to find candidate members relevant for the gastrin hormone signaling network model. We show how a combination of specific query definitions and additional selection criteria derived from gene expression data and prior knowledge concerning candidate proteins can be used to retrieve a set of proteins that constitute valid candidates for regulatory network extensions. Semantic web technologies provide the means for processing and integrating various heterogeneous information sources. The GeXKB offers biologists such an integrated knowledge resource, allowing them to address complex biological questions pertaining to gene expression. This work illustrates how GeXKB can be used in combination with gene expression results and literature information to identify new potential candidates that may be considered for extending a gene regulatory network.

Variation in gene expression within clones of the earthworm Dendrobaena octaedra.

Directory of Open Access Journals (Sweden)

Marina Mustonen

Full Text Available Gene expression is highly plastic, which can help organisms to both acclimate and adapt to changing environments. Possible variation in gene expression among individuals with the same genotype (among clones is not widely considered, even though it could impact the results of studies that focus on gene expression phenotypes, for example studies using clonal lines. We examined the extent of within and between clone variation in gene expression in the earthworm Dendrobaena octaedra, which reproduces through apomictic parthenogenesis. Five microsatellite markers were developed and used to confirm that offspring are genetic clones of their parent. After that, expression of 12 genes was measured from five individuals each from six clonal lines after exposure to copper contaminated soil. Variation in gene expression was higher over all genotypes than within genotypes, as initially assumed. A subset of the genes was also examined in the offspring of exposed individuals in two of the clonal lines. In this case, variation in gene expression within genotypes was as high as that observed over all genotypes. One gene in particular (chymotrypsin inhibitor also showed significant differences in the expression levels among genetically identical individuals. Gene expression can vary considerably, and the extent of variation may depend on the genotypes and genes studied. Ensuring a large sample, with many different genotypes, is critical in studies comparing gene expression phenotypes. Researchers should be especially cautious inferring gene expression phenotypes when using only a single clonal or inbred line, since the results might be specific to only certain genotypes.

Dlx homeobox gene family expression in osteoclasts.

Science.gov (United States)

Lézot, F; Thomas, B L; Blin-Wakkach, C; Castaneda, B; Bolanos, A; Hotton, D; Sharpe, P T; Heymann, D; Carles, G F; Grigoriadis, A E; Berdal, A

2010-06-01

Skeletal growth and homeostasis require the finely orchestrated secretion of mineralized tissue matrices by highly specialized cells, balanced with their degradation by osteoclasts. Time- and site-specific expression of Dlx and Msx homeobox genes in the cells secreting these matrices have been identified as important elements in the regulation of skeletal morphology. Such specific expression patterns have also been reported in osteoclasts for Msx genes. The aim of the present study was to establish the expression patterns of Dlx genes in osteoclasts and identify their function in regulating skeletal morphology. The expression patterns of all Dlx genes were examined during the whole osteoclastogenesis using different in vitro models. The results revealed that Dlx1 and Dlx2 are the only Dlx family members with a possible function in osteoclastogenesis as well as in mature osteoclasts. Dlx5 and Dlx6 were detected in the cultures but appear to be markers of monocytes and their derivatives. In vivo, Dlx2 expression in osteoclasts was examined using a Dlx2/LacZ transgenic mouse. Dlx2 is expressed in a subpopulation of osteoclasts in association with tooth, brain, nerve, and bone marrow volumetric growths. Altogether the present data suggest a role for Dlx2 in regulation of skeletal morphogenesis via functions within osteoclasts. (c) 2010 Wiley-Liss, Inc.

PRAME Gene Expression in Acute Leukemia and Its Clinical Significance

International Nuclear Information System (INIS)

Ding, Kai; Wang, Xiao-ming; Fu, Rong; Ruan, Er-bao; Liu, Hui; Shao, Zong-hong

2012-01-01

To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia (AL) and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics (gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype) of the patients were performed. The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia (AML, n=27), and in 28.6% of the patients with acute lymphoblastic leukemia (ALL, n=7), but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M 3 , 33.3% in M 2 , and 28.6% in M 5 . Gene expression was also found to be correlated with CD15 and CD33 expression and abnormal karyotype, but not with age, gender, white blood count or percentage of blast cells. The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia

Epigenetic regulation on the gene expression signature in esophagus adenocarcinoma.

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Xi, Ting; Zhang, Guizhi

2017-02-01

Understanding the molecular mechanisms represents an important step in the development of diagnostic and therapeutic measures of esophagus adenocarcinoma (NOS). The objective of this study is to identify the epigenetic regulation on gene expression in NOS, shedding light on the molecular mechanisms of NOS. In this study, 78 patients with NOS were included and the data of mRNA, miRNA and DNA methylation of were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis between NOS and controls was performed in terms of gene expression, miRNA expression, and DNA methylation. Bioinformatic analysis was followed to explore the regulation mechanisms of miRNA and DNA methylationon gene expression. Totally, up to 1320 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs were identified. 240 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. 101 DEGs were found to be highlymethylated in CpG islands. Then, 8 differentially methylated genes (DMGs) were selected, which showed down-regulated expression in NOS. Among of these genes, 6 genes including ADHFE1, DPP6, GRIA4, CNKSR2, RPS6KA6 and ZNF135 were target genes of differentially expressed miRNAs (hsa-mir-335, hsa-mir-18a, hsa-mir-93, hsa-mir-106b and hsa-mir-21). The identified altered miRNA, genes and DNA methylation site may be applied as biomarkers for diagnosis and prognosis of NOS. Copyright © 2016 Elsevier GmbH. All rights reserved.

Codon usage and amino acid usage influence genes expression level.

Science.gov (United States)

Paul, Prosenjit; Malakar, Arup Kumar; Chakraborty, Supriyo

2018-02-01

Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE)

Science.gov (United States)

Sharon, Dror; Blackshaw, Seth; Cepko, Constance L.; Dryja, Thaddeus P.

2002-01-01

We used the serial analysis of gene expression (SAGE) technique to catalogue and measure the relative levels of expression of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium (RPE) from one or both of two humans, aged 88 and 44 years. The cone photoreceptor contribution to all transcription in the retina was found to be similar in the macula versus the retinal periphery, whereas the rod contribution was greater in the periphery versus the macula. Genes encoding structural proteins for axons were found to be expressed at higher levels in the macula versus the retinal periphery, probably reflecting the large proportion of ganglion cells in the central retina. In comparison with the younger eye, the peripheral retina of the older eye had a substantially higher proportion of mRNAs from genes encoding proteins involved in iron metabolism or protection against oxidative damage and a substantially lower proportion of mRNAs from genes encoding proteins involved in rod phototransduction. These differences may reflect the difference in age between the two donors or merely interindividual variation. The RPE library had numerous previously unencountered tags, suggesting that this cell type has a large, idiosyncratic repertoire of expressed genes. Comparison of these libraries with 100 reported nonocular SAGE libraries revealed 89 retina-specific or enriched genes expressed at substantial levels, of which 14 are known to cause a retinal disease and 53 are RPE-specific genes. We expect that these libraries will serve as a resource for understanding the relative expression levels of genes in the retina and the RPE and for identifying additional disease genes. PMID:11756676

Disease gene characterization through large-scale co-expression analysis.

Directory of Open Access Journals (Sweden)

Allen Day

2009-12-01

Full Text Available In the post genome era, a major goal of biology is the identification of specific roles for individual genes. We report a new genomic tool for gene characterization, the UCLA Gene Expression Tool (UGET.Celsius, the largest co-normalized microarray dataset of Affymetrix based gene expression, was used to calculate the correlation between all possible gene pairs on all platforms, and generate stored indexes in a web searchable format. The size of Celsius makes UGET a powerful gene characterization tool. Using a small seed list of known cartilage-selective genes, UGET extended the list of known genes by identifying 32 new highly cartilage-selective genes. Of these, 7 of 10 tested were validated by qPCR including the novel cartilage-specific genes SDK2 and FLJ41170. In addition, we retrospectively tested UGET and other gene expression based prioritization tools to identify disease-causing genes within known linkage intervals. We first demonstrated this utility with UGET using genetically heterogeneous disorders such as Joubert syndrome, microcephaly, neuropsychiatric disorders and type 2 limb girdle muscular dystrophy (LGMD2 and then compared UGET to other gene expression based prioritization programs which use small but discrete and well annotated datasets. Finally, we observed a significantly higher gene correlation shared between genes in disease networks associated with similar complex or Mendelian disorders.UGET is an invaluable resource for a geneticist that permits the rapid inclusion of expression criteria from one to hundreds of genes in genomic intervals linked to disease. By using thousands of arrays UGET annotates and prioritizes genes better than other tools especially with rare tissue disorders or complex multi-tissue biological processes. This information can be critical in prioritization of candidate genes for sequence analysis.

Molecular Imaging of Gene Expression and Efficacy following Adenoviral-Mediated Brain Tumor Gene Therapy

Directory of Open Access Journals (Sweden)

Alnawaz Rehemtulla

2002-01-01

Full Text Available Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD along with an optical reporter gene (luciferase. Following intratumoral injection of the vector into orthotopic 9L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging

Screening for interaction effects in gene expression data.

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Peter J Castaldi

Full Text Available Expression quantitative trait (eQTL studies are a powerful tool for identifying genetic variants that affect levels of messenger RNA. Since gene expression is controlled by a complex network of gene-regulating factors, one way to identify these factors is to search for interaction effects between genetic variants and mRNA levels of transcription factors (TFs and their respective target genes. However, identification of interaction effects in gene expression data pose a variety of methodological challenges, and it has become clear that such analyses should be conducted and interpreted with caution. Investigating the validity and interpretability of several interaction tests when screening for eQTL SNPs whose effect on the target gene expression is modified by the expression level of a transcription factor, we characterized two important methodological issues. First, we stress the scale-dependency of interaction effects and highlight that commonly applied transformation of gene expression data can induce or remove interactions, making interpretation of results more challenging. We then demonstrate that, in the setting of moderate to strong interaction effects on the order of what may be reasonably expected for eQTL studies, standard interaction screening can be biased due to heteroscedasticity induced by true interactions. Using simulation and real data analysis, we outline a set of reasonable minimum conditions and sample size requirements for reliable detection of variant-by-environment and variant-by-TF interactions using the heteroscedasticity consistent covariance-based approach.

Anterior-posterior regionalized gene expression in the Ciona notochord.