Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation of neutralizing and non-neutralizing monoclonal antibodies against H7N9 influenza virus

ABSTRACT The H7N9 viruses have been circulating for six years. The insertion of a polybasic cleavage site in the haemagglutinin (HA) protein of H7N9 has resulted in the emergence of a highly pathogenic (HP) avian influenza virus. Currently, there are limited studies on neutralizing monoclonal antibodies(mAbs) against HP H7N9 AIVs. In this study, mice were immunized with inactivated H7N9 vaccine of A/ZJU01/PR8/2013 to produce murine mAbs. Finally, two murine mAbs against the HA of low pathogenic (LP) virus were produced and characterized. Characterization included determining mAbs binding breadth and affinity, in vitro neutralization capacity, and potential in vivo protection. Two of these mAbs, 1H10 and 2D1, have been identified to have therapeutic and prophylactic efficacy against the HP strain in mouse passive transfer-viral challenge experiments. The mAb 1H10 was most efficacious, even if the treatment-time was as late as 72 h post-infection, or the therapeutic dose was as low as 1 mg/kg; and it was confirmed to have haemagglutination inhibition and neutralizing activity on both LP-and HP-H7N9 strains. Further study indicated that the protection provided by 2D1 was mediated by antibody-dependent cellular cytotoxicity. The mAbs described here provide promising results and merit further development into potential antiviral therapeutics for H7N9 infection.
Spring seasonal pattern of primary production in the Gulf of Riga (Baltic Sea) after a mild winter

ABSTRACT: Spring phytoplankton production was estimated by a light and dark bottle oxygen technique in the southern part of the Gulf of Riga during spring 2014. The main study objective was to determine factors that define the spring primary productivity by analyzing the pattern of primary production and changes in succession of phytoplankton species along with environmental factors. Spring phytoplankton production was estimated by a light and dark bottle oxygen technique in the southern part of the Gulf of Riga during spring 2014. The main study objective was to determine factors that define the spring primary productivity by analyzing the pattern of primary production and changes in succession of phytoplankton species along with environmental factors. The productivity was measured after an untypically mild winter without ice-cover on the Gulf of Riga and spring flooding, which resulted in large amounts of terrestrial nutrients retained in the catchment area. At that time precipitation played a major role in riveroriginated nutrient inflow in the study area. A vague diatom bloom was stretched throughout April, followed by increase in biomass of dinoflagellate Peridiniella catenata and autotrophic ciliate Mesodinium rubrum. The total amount of spring primary production (MarchMay) reached 116.3 to 127.2 g C m–2 in the southern region of the Gulf of Riga. Our results suggest that diatoms contributed most to the “new” production and net primary production, whereas dinoflagellate P. catenata and autotrophic ciliate M. rubrum vernal production was mostly based on regenerated nutrients, although showing also the highest respiration rates.
Current Understanding of RAD52 Functions: Fundamental and Therapeutic Insights

In this Special Issue, we would like to focus on the various functions of the RAD52 helicase-like protein and the current implications of such findings for cancer treatment. Over the last few years, various laboratories have discovered particular activities of mammalian RAD52—both in S and M phase—that are distinct from the auxiliary role of yeast RAD52 in homologous recombination. At DNA double-strand breaks, RAD52 was demonstrated to spur alternative pathways to compensate for the loss of homologous recombination functions. At collapsed replication forks, RAD52 activates break-induced replication. In the M phase, RAD52 promotes the finalization of DNA replication. Its compensatory role in the resolution of DNA double-strand breaks has put RAD52 in the focus of synthetic lethal strategies, which is particularly relevant for cancer treatment.
Terms and Measures of Cognitive Health Associated With Dementia and Alzheimer’s Disease: A Scoping Review

The Healthy Brain Initiative: National Public Health Road Map to Maintaining Cognitive Health (2007) called on the research community to disseminate its work on cognitive aging and cognitive health. The purpose of this scoping review was to (1) identify terminology that cognitive, social, and behavioral scientists use to describe cognitive aging and cognitive health, in association with dementia and Alzheimer’s disease, among older adults; (2) demonstrate how such terms are defined; and (3) illustrate how these constructs are measured in research settings. Empirical studies published 2007–2018 were examined for terminology, definitions, disciplinary orientation, and measurement mechanisms. Analysis of the corpus and a detailed review of the terms “cognitive impairment” and “mild cognitive impairment” reveal that formal definitions are provided infrequently and measurement of constructs ranges widely. Overall, the variability in terminology, definitions, and measures reflects a need for greater specificity in research communication, such that cross-disciplinary collaboration can be facilitated.
Endoplasmic reticulum–associated degradation regulates mitochondrial dynamics in brown adipocytes

Organelle cross-talk Endoplasmic reticulum (ER)–associated degradation (ERAD) is a quality control mechanism that allows for targeted degradation of proteins in the ER. Zhou et al. found that a particular protein complex in ERAD, Sel1L-Hrd1, regulates the dynamics of another organelle, the mitochondrion, by altering ER-mitochondria contacts. Three-dimensional high-resolution imaging in brown adipocytes from cold-challenged mice revealed that defective ERAD led to the formation of enlarged and abnormally shaped mitochondria with perforating ER tubules. The authors explored the consequences of ERAD deficiency on mitochondrial function and thermogenesis, which provides insights into ERADmediated ER-mitochondrial cross-talk and advances our understanding of the physiological importance of interorganelle contact. Science, this issue p. 54 A regulatory mechanism underlying endoplasmic reticulum–mitochondria communication is dissected in mouse fat cells. The endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known as mitochondria-associated membranes (MAMs). Here, we used three-dimensional high-resolution imaging to investigate the formation of pleomorphic “megamitochondria” with altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ER-associated protein degradation (ERAD). Mice with ERAD deficiency in brown adipocytes were cold sensitive and exhibited mitochondrial dysfunction. ERAD deficiency affected ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover of the MAM protein, sigma receptor 1 (SigmaR1). Thus, our study provides molecular insights into ER-mitochondrial cross-talk and expands our understanding of the physiological importance of Sel1L-Hrd1 ERAD.
Long term results of anterior cruciate ligament reconstruction

The anterior cruciate ligament is the weaker of the two cruciate ligaments stabilizing the knee joint, and therefore gets torn easier than the posterior cruciate ligament. Reconstruction of ACL and restoration of musculoskeletal function is a fundamental goal of orthopaedic treatment. This study was conducted to determine pattern of anterior cruciate ligament injury and its management in a tertiary care center and to assess the long term outcome of knee function after anterior cruciate Ligament reconstruction. 28 patients with ACL injury were included. In this study. A detailed history regarding the pattern of injury was noted and ACL reconstruction was done using BT Bone graft with mini-arthrotomy and arthroscopic assisted ACL reconstruction. The clinical follow-up evaluation was done following the surgery and postoperative rehabilitation. International Knee Documentation Committee (IKDC) and Lysholm Score were used to assess the functional outcome. The mean age of the study subjects was 30.6±7.3 years and majority were males. Majority of the ACL injury was sports related and was on the right knee. 64% underwent arthroscopic assisted ACL reconstruction; majority of them had normal range of motion of the knee. According to the IKDC rating scale, 80% of the patients had normal or nearly normal final outcome. The mean Lysholm score was 80. About 10 of the patients had anterior knee pain, as classified by the IKDC. Patients with early reconstruction had less degenerative changes in the tibiofemoral joint, were subjectively more satisfied to the result, and could return to the pre-injury level of activities. Our present study concludes that most common age group involved was 20-30 years and ACL injury was more common among males. Patients with an early ACL reconstruction were more satisfied with the end result. Also, ACL reconstruction techniques using BTB auto graft leads to good ligamentous stability and function of the knee. Mild anterior knee pain and osteoarthritis after reconstruction was a common
The association of antidepressant monotherapy and weight change in a Middle Eastern psychiatric population

Genetic and lifestyle factors influence weight changes secondary to antidepressants. However, the association between antidepressants and weight changes is seldom studied in Middle Eastern populations who have a unique genetic, lifestyle and dietary profile. This is a chart-based retrospective longitudinal study that describes the 6-month evolution of weight in outpatient Lebanese adults initiated on serotonin reuptake inhibitor (SRI) antidepressant monotherapy, with the exclusion of confounders with metabolic implications. A linear mixed model was used to estimate the association of weight with time. Demographic factors were tested for interaction with the model. The sample consisted of 200 antidepressant trials. After adjusting for baseline weight, age, and sex, weight did not change significantly from week 1 to week 4 (P = 0.530) but significantly increased by 0.15 kg/week from week 4 to week 24 (P < 0.05). Sex, baseline weight, alcohol use, tobacco use, and presence of metabolic condition(s) did not affect weight change (P > 0.05). The same changes were observed across all SRIs and diagnoses. Our results show that SRI monotherapy is associated with weight gain throughout the treatment course in a Middle Eastern population. We recommend judicious prescription of SRIs and clinical vigilance over weight throughout the course of treatment in these populations.
Long term control stereotactic body radiotherapy (SBRT) for oligometastatic colorectal cancer: a single center study.

BACKGROUND To evaluate survival after stereotactic body radiotherapy (SBRT) as radical treatment for metastases of colorectal cancer (CRC) and to identify prognostic factors after treatment. METHODS Patients with metastatic CRC treated with SBRT on metastatic lesions were retrospectively analyzed between February 2012 and August 2016 at the General University Hospital of Valencia. The follow-up was carried out until July 15, 2018. The data have been collected in a database. Patients may have received prior systemic therapy and/or resection of metastatic disease. Endpoints were timed from end of SBRT and included overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. RESULTS A total of 49 patients were identified. Before SBRT, 77.5% of the patients have received systemic therapy and 65.2% surgery for metastatic disease. Of metastatic lesions treated with SBRT 53.1% were located in the lung, 30.6% in the liver and 16.3% in other locations. Median survival were: PFS after treatment with SBRT was 9.9 months (95% CI: 4.64-15.1) and the median OS was 28.9 months (95% CI: 19.0-38.7). No relapses were observed in 20% of the patients after SBRT. The treatment was well tolerated and no patient had grade 3 or 4 adverse effects. Right colon [HR 16.53 (95% CI: 3.11-87.87), P value 0.001] and higher tumor stage (III-IV) [HR 12.30 (95% CI: 2.10-71.92), P value 0.005] showed a lower OS in a multivariate analysis. CONCLUSIONS SBRT for oligometastatic disease is an effective option for patients with advanced CRC, with encorauging survival outcomes. However, a definitive validation in large randomized studies is required.
Casein Ingestion Does Not Increase Muscle Connective Tissue Protein Synthesis Rates

Supplemental digital content is available in the text. ABSTRACT Purpose This study aimed to assess the effect of dietary protein ingestion on intramuscular connective tissue protein synthesis rates during overnight recovery from a single bout of resistance exercise. Methods Thirty-six healthy, young males were randomly assigned to one of three treatments. One group ingested 30 g intrinsically L-[1-13C]-phenylalanine-labeled casein protein before sleep (PRO, n = 12). The other two groups performed a bout of resistance exercise in the evening and ingested either placebo (EX, n = 12) or 30 g intrinsically L-[1-13C]-phenylalanine-labeled casein protein before sleep (EX + PRO, n = 12). Continuous intravenous infusions of L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine were applied, and blood and muscle tissue samples were collected to assess connective tissue protein synthesis rates and dietary protein-derived amino acid incorporation in the connective tissue protein fraction. Results Resistance exercise resulted in higher connective tissue protein synthesis rates when compared with rest (0.086 ± 0.017%·h−1 [EX] and 0.080 ± 0.019%·h−1 [EX + PRO] vs 0.059 ± 0.016%·h−1 [PRO]; P < 0.05). Postexercise casein protein ingestion did not result in higher connective tissue protein synthesis rates when compared with postexercise placebo ingestion (P = 1.00). Dietary protein-derived amino acids were incorporated into the connective tissue protein fraction at rest, and to a greater extent during recovery from exercise (P = 0.002). Conclusion Resistance exercise increases intramuscular connective tissue protein synthesis rates during overnight sleep, with no further effect of postexercise protein ingestion. However, dietary protein-derived amino acids are being used as precursors to support de novo connective tissue protein synthesis.
Tumor cell–organized fibronectin maintenance of a dormant breast cancer population

Barney et al. used biomaterials to uncover a role for fibronectin in preventing breast cancer cell escape from dormancy. Tumors can undergo long periods of dormancy, with cancer cells entering a largely quiescent, nonproliferative state before reactivation and outgrowth. To understand the role of the extracellular matrix (ECM) in regulating tumor dormancy, we created an in vitro cell culture system with carefully controlled ECM substrates to observe entrance into and exit from dormancy with live imaging. We saw that cell populations capable of surviving entrance into long-term dormancy were heterogeneous, containing quiescent, cell cycle–arrested, and actively proliferating cells. Cell populations capable of entering dormancy formed an organized, fibrillar fibronectin matrix via αvβ3 and α5β1 integrin adhesion, ROCK-generated tension, and TGFβ2 stimulation, and cancer cell outgrowth after dormancy required MMP-2–mediated fibronectin degradation. We propose this approach as a useful, in vitro method to study factors important in regulating dormancy, and we used it here to elucidate a role for fibronectin deposition and MMP activation.
Rural-Urban Differences in Neuroimmune Biomarkers and Health Status Among Women Living With Breast Cancer

Supplemental digital content is available in the text. Background Because of chronic emotional and psychosocial stressors following breast cancer (BC) treatment, BC survivors are at risk of neuroimmune dysfunction in survivorship. Rural BC survivors experience more health disparities than urban BC survivors. Rural-urban residence as a variable on neuroimmune activity in extended BC survivorship continuum has not been explored. Objective To report the feasibility of studying relationships between neuroimmune activity and perceived health in rural and urban BC survivors. Methods Data from a pilot study of BC survivors (n = 41) were analyzed. Participants were rural (n = 16) and urban (n = 25). Participants completed Medical Outcomes Study Short-Form Version 2 Health Survey questionnaires and provided salivary specimens for analysis of salivary α-amylase (sAA), cortisol, and interleukin 6 (IL-6). Rural-Urban Commuting Area Codes were used to determine rural or urban residence. Results Differences in immune activity were observed between rural and urban BC survivors (U = 34, P < .05). No rural-urban group differences in neuroendocrine activity were observed. Relationships were observed between perceptions of mental health and sAA (P < .05) in rural BC survivors and between perceptions of mental health and IL-6 (P < .05) in urban BC survivors. Interleukin 6 was positively associated with perceptions of physical health (P < .05) in rural BC survivors. Conclusion Pilot data suggest rural-urban residence may be a factor in relationships between neuroimmune function (ie, sAA and IL-6) and perceived health status, particularly social functioning in women with BC. Additional studies with powered designs are indicated. Implications for Practice Although evidence is limited, data support the feasibility of studying relationships between sAA and IL-6 and perceptions of health in women with BC.
High-throughput single-cell live imaging of photobiomodulation with multispectral near-infrared lasers in cultured T cells

Abstract. Significance: Photobiomodulation is a well-established therapeutic modality. However, the mechanism of action is poorly understood, due to lack of research in the causal relationship between the near-infrared (NIR) light irradiation and its specific biological effects, hindering broader applications of this technology. Aim: Since biological chromophores typically show several absorption peaks, we determined whether specific effects of photobiomodulation are induced with a combination of two wavelengths at a certain range of irradiance only, rather than a single wavelength of NIR light. Approach: In order to analyze a wide array of combinations of multispectral NIR light at various irradiances efficiently, we developed a new optical platform equipped with two distinct wavelengths of NIR lasers by high-throughput multiple dosing for single-cell live imaging. Two wavelengths of 1064 and 1270 nm were selected based on their photobiomodulatory effects reported in the literature. Results: A specific combination of wavelengths at low irradiances (250 to 400 mW / cm2 for 1064 nm and 55 to 65 mW / cm2 for 1270 nm) modulates mitochondrial retrograde signaling, including intracellular calcium and reactive oxygen species in T cells. The time-dependent density functional theory computation of binding of nitric oxide (NO) to cytochrome c oxidase indicates that the illumination with NIR light could result in the NO release, which might be involved in these changes. Conclusions: This optical platform is a powerful tool to study causal relationship between a specific parameter of NIR light and its biological effects. Such a platform is useful for a further mechanistic study on not only photobiomodulation but also other modalities in photomedicine.
Soluble Epoxide Hydrolase 2 Expression Is Elevated in Obese Humans and Decreased by Physical Activity

Epoxide hydrolase 2 (EPHX2) is an emerging therapeutic target in several immunometabolic disorders. EPHX2 metabolizes anti-inflammatory epoxyeicosatrienoic acids into pro-inflammatory diols. The contribution of EPHX2 activity to human obesity remains unexplored. We compared the expression of EPHX2 between lean and obese humans (n = 20 each) in subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs) using RT-PCR, Western Blot analysis, immunohistochemistry, and confocal microscopy before and after a 3-month physical activity regimen. We also assessed EPHX2 levels during preadipocyte differentiation in humans and mice. EPHX2 mRNA and protein expression were significantly elevated in obese subjects, with concomitant elevated endoplasmic reticulum (ER) stress components (the 78-kDa glucose-regulated protein; GRP78, and the Activating transcription factor 6; ATF6) and inflammatory markers (Tumor necrosis factor-α; TNFα, and Interleukin 6; IL6) as compared to controls (p < 0.05). EPHX2 mRNA levels strongly correlated with adiposity markers. In obese individuals, physical activity attenuated EPHX2 expression levels in both the SAT and PBMCs, with a parallel decrease in ER stress and inflammation markers. EPHX2 expression was also elevated during differentiation of both human primary and 3T3-L1 mouse preadipocytes. Mediators of cellular stress (palmitate, homocysteine, and macrophage culture medium) also increased EPHX2 expression in 3T3-L1 preadipocytes. Our findings suggest that EPHX2 upregulation is linked to ER stress in adiposity and that physical activity may attenuate metabolic stress by reducing EPHX2 expression.
Dissociable effects of visual crowding on the perception of color and motion

Significance Our peripheral vision is primarily limited by crowding, the disruption to object recognition that arises in clutter. Crowding is widely assumed to be a singular process, affecting all the features (e.g., orientation, motion, color) within an object simultaneously. In contrast, we observe a double dissociation whereby observers make errors regarding the color of a crowded object while correctly judging its direction, and vice versa. This dissociation can be reproduced by a population-coding model in which the direction and hue of target/flanker elements are pooled independently. The selective disruption of some object features independently of others rules out a singular crowding mechanism, posing problems for high-level crowding theories and suggesting that the underlying mechanisms may be distributed throughout the visual system. Our ability to recognize objects in peripheral vision is fundamentally limited by crowding, the deleterious effect of clutter that disrupts the recognition of features ranging from orientation and color to motion and depth. Previous research is equivocal on whether this reflects a singular process that disrupts all features simultaneously or multiple processes that affect each independently. We examined crowding for motion and color, two features that allow a strong test of feature independence. “Cowhide” stimuli were presented 15° in peripheral vision, either in isolation or surrounded by flankers to give crowding. Observers reported either the target direction (clockwise/counterclockwise from upward) or its hue (blue/purple). We first established that both features show systematic crowded errors (biased predominantly toward the flanker identities) and selectivity for target–flanker similarity (with reduced crowding for dissimilar target/flanker elements). The multiplicity of crowding was then tested with observers identifying both features. Here, a singular object-selective mechanism predicts that when crowding is weak for one feature and strong for the other that crowding should be all-or-none for both. In contrast, when crowding was weak for color and strong for motion, errors were reduced for color but remained for motion, and vice versa with weak motion and strong color crowding. This double dissociation reveals that crowding disrupts certain combinations of visual features in a feature-specific manner, ruling out a singular object-selective mechanism. Thus, the ability to recognize one aspect of a cluttered scene, like color, offers no guarantees for the correct recognition of other aspects, like motion.