Genetic mapping of quantitative trait loci associated with drought tolerance in chickpea (Cicer arietinum L.).

Elucidation of the genetic basis of drought tolerance is vital for genomics-assisted breeding of drought tolerant crop varieties. Here, we used genotyping-by-sequencing (GBS) to identify single nucleotide polymorphisms (SNPs) in recombinant inbred lines (RILs) derived from a cross between a drought tolerant chickpea variety, Pusa 362 and a drought sensitive variety, SBD 377. The GBS identified a total of 35,502 SNPs and subsequent filtering of these resulted in 3237 high-quality SNPs included in the eight linkage groups. Fifty-one percent of these SNPs were located in the genic regions distributed throughout the genome. The high density linkage map has total map length of 1069 cm with an average marker interval of 0.33 cm. The linkage map was used to identify 9 robust and consistent QTLs for four drought related traits viz. membrane stability index, relative water content, seed weight and yield under drought, with percent variance explained within the range of 6.29%-90.68% and LOD scores of 2.64 to 6.38, which were located on five of the eight linkage groups. A genomic region on LG 7 harbors quantitative trait loci (QTLs) explaining > 90% phenotypic variance for membrane stability index, and > 10% PVE for yield. This study also provides the first report of major QTLs for physiological traits such as membrane stability index and relative water content for drought stress in chickpea. A total of 369 putative candidate genes were identified in the 6.6 Mb genomic region spanning these QTLs. In-silico expression profiling based on the available transcriptome data revealed that 326 of these genes were differentially expressed under drought stress. KEGG analysis resulted in reduction of candidate genes from 369 to 99, revealing enrichment in various signaling pathways. Haplotype analysis confirmed 5 QTLs among the initially identified 9 QTLs. Two QTLs, qRWC1.1 and qYLD7.1, were chosen based on high SNP density. Candidate gene-based analysis revealed distinct haplotypes in qYLD7.1 associated with significant phenotypic differences, potentially linked to pathways for secondary metabolite biosynthesis. These identified candidate genes bolster defenses through flavonoids and phenylalanine-derived compounds, aiding UV protection, pathogen resistance, and plant structure.The study provides novel genomic regions and candidate genes which can be utilized in genomics-assisted breeding of superior drought tolerant chickpea cultivars.

Interferon-Induced Bone Marrow Stromal Antigen 2 (BST2) Is A Functional Tumor-Initiating Cell Marker In Triple-Negative Breast Cancer.

Tumor-initiating cells (TIC) are a tumor cell subpopulation thought to be responsible for therapeutic resistance and metastasis. Using a S ignal T ransducer and A ctivator of T ranscription (STAT) reporter, and a STAT-responsive lineage tracing system, we enriched for cells with enhanced mammosphere-forming potential in some, but not all, triple-negative breast cancer xenograft models (TNBC) indicating TIC-related and TIC-independent functions for STAT signaling. Single-cell RNA sequencing (scRNA-seq) of reporter-tagged xenografts identified a common interferon-associated transcriptional state, previously linked to inflammation and macrophage differentiation, in TIC. Similar transcriptional states exist in human breast cancer patient scRNA-seq datasets. Flow cytometric sorting using bone marrow stromal cell antigen 2 (BST2), a marker of this state, enriched for TIC, and BST2 knockdown reduced mammosphere-forming potential. These results suggest TIC may exploit the interferon response pathway to promote their activity in TNBC. Our results lay the groundwork to target interferon-associated pathways in TIC in a subset of TNBC.

PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

BACKGROUND: Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known. METHODS: We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from Prox1ΔVEC mice in which Prox1 was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency. RESULTS: Histological analysis revealed that the aortic and mitral valves of Prox1ΔVEC mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of Prox1ΔVEC mice are stenotic. FOXC2 was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of Prox1ΔVEC mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of Prox1ΔVEC mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of Prox1ΔVEC mice. CONCLUSIONS: PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.

Sentimental analysis from imbalanced code-mixed data using machine learning approaches.

Knowledge discovery from various perspectives has become a crucial asset in almost all fields. Sentimental analysis is a classification task used to classify the sentence based on the meaning of their context. This paper addresses class imbalance problem which is one of the important issues in sentimental analysis. Not much works focused on sentimental analysis with imbalanced class label distribution. The paper also focusses on another aspect of the problem which involves a concept called "Code Mixing". Code mixed data consists of text alternating between two or more languages. Class imbalance distribution is a commonly noted phenomenon in a code-mixed data. The existing works have focused more on analyzing the sentiments in a monolingual data but not in a code-mixed data. This paper addresses all these issues and comes up with a solution to analyze sentiments for a class imbalanced code-mixed data using sampling technique combined with levenshtein distance metrics. Furthermore, this paper compares the performances of various machine learning approaches namely, Random Forest Classifier, Logistic Regression, XGBoost classifier, Support Vector Machine and Naïve Bayes Classifier using F1- Score.

Exploring invasive weed biochar as soil amendment: A study on fodder oats productivity and soil biological properties.

Biochar is known for the improvement of soil health, fertility, crop productivity, and quality in many agro-ecosystems globally, but information regarding fodder yield, quality, and soil microbial activity responses to biochar application remains very limited. The objective of this study was to prepare biochar from invasive weeds, i.e., Parthenium hysterophorus L. and Lantana camara L., and use it as a soil amendment along with inorganic fertilizers for oats (Avena sativa L.) growth, fodder yield, quality, and soil microbial activities in a two-year pot experiment. Treatments were comprised of control, 100% RDF (Recommended dose of fertilizers), 75% RDF along with three doses (2.5, 5.0, and 10 t/ha) of Parthenium hysterophorus L. biochar (PB) and Lantana camara L. biochar (LB), PB (10 t/ha), and LB (10 t/ha). Results showed that application of 75% RDF along with 10 t/ha LB gave significantly higher green (∼8%) and dry (∼7.8%) fodder yield and crude protein (∼6%) and decreased acid detergent fibre (ADF) and neutral detergent fibre (NDF) by 5.70 and 6.04% as compared to the 100% RDF treatment. The same treatment had a significantly higher population of bacteria (7.33 × 108 colony forming unit (CFU)/g soil), alkaline phosphatase activity (19.56 µg pNP/g soil/h), microbial biomass carbon (156.67 µg/g soil) and dehydrogenase activity (12.59 µg TPF/g/24 h), whereas the maximum fungal population (13.33 × 104 CFU/g soil) and acid phosphatase activity (14.45 µg pNP/g soil/h) were found in 75% RDF along with 10 t/ha PB and control treatment, respectively. This study concluded that application of invasive weed biochar along with inorganic fertilizers can benefit fodder yield and quality of oats by increasing plant height and number of tillers directly and by improving nutrient availability and water holding capacity (WHC) of soil indirectly, besides improving soil health. The findings from this study will provide a potential strategy for invasive weed management.

GATA2 regulates blood/lymph separation in a platelet-dependent and lymphovenous valve-independent manner.

INTRODUCTION: Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation. OBJECTIVES: The primary objective of this work is to determine whether platelets can regulate blood/lymph separation independently of LVVs. METHODS: The transcription factor GATA2 is necessary for the development of both LVVs and hematopoietic stem cells. Using various endothelial- and hematopoietic cell expressed Cre-lines, we conditionally deleted Gata2. We hypothesized that this strategy would identify the tissue- and time-specific roles of GATA2 and reveal whether platelets and LVVs can independently regulate blood/lymph separation. RESULTS: Lymphatic vasculature-specific deletion of Gata2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature. CONCLUSION: GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.

Promoting Lymphangiogenesis and Lymphatic Growth and Remodeling to Treat Cardiovascular and Metabolic Diseases.

Lymphatic vessels are low-pressure, blind-ended tubular structures that play a crucial role in the maintenance of tissue fluid homeostasis, immune cell trafficking, and dietary lipid uptake and transport. Emerging research has indicated that the promotion of lymphatic vascular growth, remodeling, and function can reduce inflammation and diminish disease severity in several pathophysiologic conditions. In particular, recent groundbreaking studies have shown that lymphangiogenesis, which describes the formation of new lymphatic vessels from the existing lymphatic vasculature, can be beneficial for the alleviation and resolution of metabolic and cardiovascular diseases. Therefore, promoting lymphangiogenesis represents a promising therapeutic approach. This brief review summarizes the most recent findings related to the modulation of lymphatic function to treat metabolic and cardiovascular diseases such as obesity, myocardial infarction, atherosclerosis, and hypertension. We also discuss experimental and therapeutic approaches to enforce lymphatic growth and remodeling as well as efforts to define the molecular and cellular mechanisms underlying these processes.

Lack of embryonic homozygous or adult heterozygous lymphatic phenotypes for a Sos1 mutation and lack of lymphatic embryonic phenotypes for a homozygous Cx47 mutation in mice.

We have studied the lymphatic phenotypes of 2 mutations, known to cause abnormalities of lymphatics in humans, in mice. The Cx47 R260C mutation (variably penetrant in humans heterozygous for it and causing limb lymphedema) had an adult mouse phenotype of hyperplasia and increased lymph nodes only in homozygous condition but we did not find any anatomical phenotype in day 16.5 homozygous embryos. Mice harboring the Sos1 mutation E846K (causing Noonan's in man which occasionally shows lymphatic dysplasia) had no adult heterozygous phenotype in lymphatic vessel appearance and drainage (homozygotes are early embryonic lethals) while day 16.5 heterozygous embryos also had no detectable anatomical phenotype.

Range grasses to improve soil properties, carbon sustainability, and fodder security in degraded lands of semi-arid regions.

Tropical grasses are the primary source of forage for livestock and a valuable resource for improving soil health and environmental sustainability in semi-arid regions. A study was carried out in a semi-arid region of central India to determine the short-term (6-year) impact of nine range grasses on soil physio-chemical and biological properties, carbon stock, and forage security. The experiment was carried out in a randomized block design with three replications. Results show that the majority of the grass roots were distributed in the upper soil layer (0-10 cm, 63.5-76.5 %), and then in the middle (10-20 cm, 21.3-25 %) and lower (20-30 cm, 2.2-11.5 %) layers. Perennial tussock grass (Heteropogon contortus (L.) P. Beauv. ex Roem. & Schult) had a higher root volume (2219 mm3), followed by Guinea grass [Megathyrsus maximus (Jacq.) B.K. Simon & S.W.L. Jacobs] (1860 mm3). A lower soil bulk density (BD, 1.11-1.23 g cm-3), higher gravimetric water content (GMW, 14.0-17.8 %), and soil organic carbon (0.38-0.73 %) were recorded for grass-cultivated plots compared to the barren land (1.38 g cm-3, 13.0 %, and 0.28 %, respectively). The perennial tussock grass and Guinea grass resulted in the highest soil microbial biomass carbon (SMBC, 70.1 mg kg-1 soil) and enzyme activities (dehydrogenase, 17.09 µg TPF g-1 day-1 and fluorescein diacetate activity 4.94 µg fluorescein g-1 h-1). The considerable improvement in soil properties with minimal inputs resulted in a higher sustainable yield index and carbon sustainability index in plots planted with Guinea grass (0.9 and 89.29) and perennial tussock grass (0.89 and 71.61). Therefore, the cultivation of either Guinea grass or perennial tussock grass as an intercrop or sole crop in the semi-arid environment can be an ecologically sound strategy to improve soil health, C sequestration, and fodder supply.

Predicting the Growth of F. proliferatum and F. culmorum and the Growth of Mycotoxin Using Machine Learning Approach.

In distinct parts of the food web, Fusarium culmorum and Fusarium preserving the relationship can germinate and grow zearalenone (ZEA) and fumonisins (FUM), accordingly. Antimicrobial drugs used to combat these fungi and toxic metabolites raise the risk of hazardous residue in food products, as well as the development of fungus tolerance. For modeling fungal growth and pathogenicity under separate water action (a q ) (0.96 and 0.99) and surface temp (20 and 28°C) tyrannies, several machine learning (ML) methodologies (artificial neural, regression trees, and extreme rise enhanced trees) and multiple regression model (MLR) were used also especially in comparison. GR and mycotoxin levels inside the environment often reduced as EOC concentrations grew, although some treatment in association with specific a q and temperature values caused ZEA production. In terms of predicting the growth rate of F. culmorum and F. maintaining the relationship and the production of ZEA and FUM, random forest techniques outperformed neural network models and extreme gradient boosted trees. The MLR option was the most inefficient. It is the first research to look at the ML potential of bio EVOH products containing EOCs and ambient variables of F. culmorum and F. proliferatum development, as well as the generation of zearalenone and fumonisins. The findings show that these entire novel wrapping technologies, in tandem using machine learning techniques, could be useful in predicting and controlling the dangers connected with fungal species or biotoxins in foodstuff.

Molecular Mechanisms Driving Lymphedema and Other Lymphatic Anomalies.

Lymphatic vasculature regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood. Lymphatic vasculature is also critical for lipid absorption and inflammatory response. Lymphatic vasculature is composed of lymphatic capillaries, collecting lymphatic vessels, lymphatic valves, and lymphovenous valves. Defects in any of these structures could lead to lymphatic anomalies such as lymphedema, cystic lymphatic malformation, and Gorham-Stout disease. Basic research has led to a deeper understanding of the stepwise development of the lymphatic vasculature. VEGF-C and shear stress signaling pathways have evolved as critical regulators of lymphatic vascular development. Loss-of-function and gain-of-function mutations in genes that are involved in these signaling pathways are associated with lymphatic anomalies. Importantly, drugs that target these molecules are showing outstanding efficacy in treating certain lymphatic anomalies. In this article, we summarize these exciting developments and highlight the future challenges.

A report on occurrence of Phlebotomine sand flies (Diptera: Psychodidae) and two new country records from Andaman amp; Nicobar Islands, a Union territory of India.

A cross-sectional survey was carried out to determine sand fly fauna of the Andaman and Nicobar Islands that are known for tourist attraction from different countries, due to their scenic beauty. The study area includes 40 localities, stretching from south and middle to north Andaman Islands. Sand fly collections were made from day time resting shelters such as human dwellings, cattle-shed, and bushes in fringe of villages. A total of 1055 sand flies, comprising of six species were collected. Se. (Neo.) barraudi was found to be the predominant species, comprising of 57.7% of the total. Other species found to occur were Se. (Par.) babu (27. 4%), Se. (bailyi) 8. 1%, Se. (Neo.) gemmea (4. 9%), Se. (Neo.) quatei (2. 1%) and Phlebotomus (Ana.) stantoni (0.3%). Se. (Neo.) gemmea is reported to be a vector transmitting visceral leishmaniasis and dermal leishmaniasis in southern Thailand. Se. (Neo.) gemmea and Se (Neo.) quatei are new country records adding to the existing list of sand fly fauna of India. This is the first report on sand flies from Andaman and Nicobar Islands.

Effect of SARS-CoV-2 seropositivity on antigen - specific cytokine and chemokine responses in latent tuberculosis.

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative individuals with SARS-CoV-2 seropositivity and healthy control (both LTBI and SARS-CoV-2 negative) individuals. Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG +) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1ß, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB - antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.

Dentists in India feel hopeless as a fulltime academician: A national survey.

AIMS: Assess the relationship between job satisfaction and feeling of hopelessness among dental academicians. SETTINGS AND DESIGN: Cross sectional study was conducted among dental academicians across India through email and social media using a pretested questionnaire. METHODS AND MATERIALS: An Internet-based cross-sectional survey was conducted among dental academicians via social media and electronic mail (e-mail) throughout India. Demographics, credentials and job satisfaction across five dimensions (working conditions, pay and promotional potential, work relationships, use of skills and abilities and work activities) were rated on a 5-point Likert scale and a sense of hopelessness was assessed using Brief-H-Neg scale. The results were collected using self-reported Google forms. Bivariate and multivariate analysis were performed to identify the risk towards hopelessness, and the relationship between job satisfaction and hopelessness was assessed using student's t-test. RESULTS AND CONCLUSION: The mean hopelessness score among dissatisfied faculty was 8.5 and among satisfied was 5.6 (P < 0.05). Tutors, assistants and associate professors with salary of INR <50000/month were highly dissatisfied (P < 0.05), and those willing to quit reported significantly lesser hopelessness compared to no/maybe. Regarding job satisfaction, greater hopelessness was reported with poor work relationships, poor working conditions and poor pay and promotional opportunities (P < 0.05). Dental academicians in India are highly dissatisfied with their career as a full-time teaching faculty. Willingness to quit has a positive effect on hopelessness, depicting the stress faculties experience in institutions. Job satisfaction among academicians plays a vital role in the student's dental learning experience and dissatisfaction will have huge ramifications on the quality of dental education and future graduates in India.

Biochemical and mechanical signals in the lymphatic vasculature.

Lymphatic vasculature is an integral part of the cardiovascular system where it maintains interstitial fluid balance. Additionally, lymphatic vasculature regulates lipid assimilation and inflammatory response. Lymphatic vasculature is composed of lymphatic capillaries, collecting lymphatic vessels and valves that function in synergy to absorb and transport fluid against gravitational and pressure gradients. Defects in lymphatic vessels or valves leads to fluid accumulation in tissues (lymphedema), chylous ascites, chylothorax, metabolic disorders and inflammation. The past three decades of research has identified numerous molecules that are necessary for the stepwise development of lymphatic vasculature. However, approaches to treat lymphatic disorders are still limited to massages and compression bandages. Hence, better understanding of the mechanisms that regulate lymphatic vascular development and function is urgently needed to develop efficient therapies. Recent research has linked mechanical signals such as shear stress and matrix stiffness with biochemical pathways that regulate lymphatic vessel growth, patterning and maturation and valve formation. The goal of this review article is to highlight these innovative developments and speculate on unanswered questions.

L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a pandemic. Severe disease is associated with dysfunction of multiple organs, but some infected cells do not express ACE2, the canonical entry receptor for SARS-CoV-2. Here, we report that the C-type lectin receptor L-SIGN interacted in a Ca2+-dependent manner with high-mannose-type N-glycans on the SARS-CoV-2 spike protein. We found that L-SIGN was highly expressed on human liver sinusoidal endothelial cells (LSECs) and lymph node lymphatic endothelial cells but not on blood endothelial cells. Using high-resolution confocal microscopy imaging, we detected SARS-CoV-2 viral proteins within the LSECs from liver autopsy samples from patients with COVID-19. We found that both pseudo-typed virus enveloped with SARS-CoV-2 spike protein and authentic SARS-CoV-2 virus infected L-SIGN-expressing cells relative to control cells. Moreover, blocking L-SIGN function reduced CoV-2-type infection. These results indicate that L-SIGN is a receptor for SARS-CoV-2 infection. LSECs are major sources of the clotting factors vWF and factor VIII (FVIII). LSECs from liver autopsy samples from patients with COVID-19 expressed substantially higher levels of vWF and FVIII than LSECs from uninfected liver samples. Our data demonstrate that L-SIGN is an endothelial cell receptor for SARS-CoV-2 that may contribute to COVID-19-associated coagulopathy.

Sweet Dre-ams about intersectional genetics.

Specific cell targeting with one site-specific recombinase is challenging. In this issue of Cell Stem Cell, Han et al. (2021) released a collection of Dre drivers and demonstrate how two recombinases can be combined to improve the cell specificity of lineage tracing and gene inactivation in mice.

Prevalence of early hip OA features on MRI in high-impact athletes. The femoroacetabular impingement and hip osteoarthritis cohort (FORCe) study.

OBJECTIVE: To compare early hip osteoarthritis (OA) features on magnetic resonance imaging (MRI) in high-impact athletes with and without hip and/or groin pain, and to evaluate associations between early hip OA features, the International Hip Outcome Tool (iHOT33) and Copenhagen Hip and Groin Outcome Score (HAGOS). DESIGN: This case-control study evaluated data of the femoroacetabular impingement and hip osteoarthritis cohort (FORCe). One hundred and eighty-two symptomatic (hip and/or groin pain >6 months and positive flexion-adduction-internal-rotation (FADIR) test) and 55 pain-free high-impact athletes (soccer or Australian football (AF)) without definite radiographic hip OA underwent hip MRI. The Scoring Hip Osteoarthritis with MRI (SHOMRI) method quantified and graded the severity of OA features. Each participant completed the iHOT33 and HAGOS. RESULTS: Hip and/or groin pain was associated with higher total SHOMRI (0-96) (mean difference 1.4, 95% CI: 0.7-2.2), labral score (adjusted incidence rate ratio (aIRR) 1.33, 95% CI: 1.1-1.6). Differences in prevalence of cartilage defects, labral tears and paralabral cysts between symptomatic and pain-free participants were inconclusive. There was a lower prevalence of effusion-synovitis in symptomatic participants when compared to pain-free participants (adjusted odds ratio (aOR) 0.46 (95% CI: 0.3-0.8). Early hip OA features were not associated with iHOT33 or HAGOS. CONCLUSIONS: A complex and poorly understood relationship exists between hip and/or groin pain and early hip OA features present on MRI in high-impact athletes without radiographic OA. Hip and/or groin pain was associated with higher SHOMRI and labral scores.

Dental pain, parental SARS-CoV-2 fear and distress on quality of life of 2 to 6 year-old children during COVID-19.

BACKGROUND: Coronavirus disease (COVID-19) has crippled life, families and oral healthcare delivery in India due to nationwide lockdown. AIM: Through cross-sectional design, we investigated the impact of child's dental pain, caregiver's fear of SARS-CoV-2 and parental distress on oral health-related quality of life (OHRQOL) of preschoolers during the nationwide COVID-19 pandemic lockdown. DESIGN: Preschool children self-reported their pain using Pieces of Hurt scale; caregiver SARS-CoV-2 fear was assessed using Fear of COVID-19 scale and parental distress evaluated using 4-item scale. Child's oral health was assessed using the dmft index and OHRQOL evaluated using early childhood oral health impact scale. Bivariate, multivariate regression analysis was conducted to identify predictors; statistical significance was set at 5%. RESULTS: Sample mean age was 4.58 years, and about 69% were boys. Children reporting higher pain scores (OR = 1.9) due to decayed teeth and having dmft > 5 (OR = 4.25), followed by greater parental distress (OR = 4.13) and fear of SARS-CoV-2 (OR = 3.84), were significantly associated with poor OHRQOL during the COVID-19 pandemic. CONCLUSIONS: Greater parental distress and fear of COVID-19 among caregivers, higher self-perceived dental pain among children and caries experience are associated with poor OHRQOL of preschool children during the COVID-19 pandemic.

RASA1-driven cellular export of collagen IV is required for the development of lymphovenous and venous valves in mice.

RASA1, a negative regulator of Ras-MAPK signaling, is essential for the development and maintenance of lymphatic vessel valves. However, whether RASA1 is required for the development and maintenance of lymphovenous valves (LVV) and venous valves (VV) is unknown. In this study, we show that induced disruption of Rasa1 in mouse embryos did not affect initial specification of LVV or central VV, but did affect their continued development. Similarly, a switch to expression of a catalytically inactive form of RASA1 resulted in impaired LVV and VV development. Blocked development of LVV was associated with accumulation of the basement membrane protein, collagen IV, in LVV-forming endothelial cells (EC), and could be partially or completely rescued by MAPK inhibitors and drugs that promote collagen IV folding. Disruption of Rasa1 in adult mice resulted in venous hypertension and impaired VV function that was associated with loss of EC from VV leaflets. In conclusion, RASA1 functions as a negative regulator of Ras signaling in EC that is necessary for EC export of collagen IV, thus permitting the development of LVV and the development and maintenance of VV.