Miracle-dz/UniFAR-FTUs huggingface dataset:
Vps13 is required for the packaging of the ER into autophagosomes during ER-phagy

Significance Vps13, a conserved phospholipid transporter, localizes to contact sites between the endoplasmic reticulum (ER) and different organelles. While budding yeast has one VPS13 gene, humans have four. The yeast Vps13 protein is most closely related to VPS13A and VPS13C. VPS13A localizes to ER–mitochondria contact sites, while VPS13C resides at ER–late endosome contact sites. Here we report that the vps13Δ mutant is defective in the selective autophagy of ER (ER-phagy). In the absence of Vps13, the ER accumulates at late endosomes and fails to be packaged into autophagosomes. These findings highlight the importance of Vps13 function at late endosomes in ER-phagy, and may have implications for understanding the role of VPS13C, which has been linked to early-onset Parkinson’s disease. Endoplasmic reticulum (ER) macroautophagy (hereafter called ER-phagy) uses autophagy receptors to selectively degrade ER domains in response to starvation or the accumulation of aggregation-prone proteins. Autophagy receptors package the ER into autophagosomes by binding to the ubiquitin-like yeast protein Atg8 (LC3 in mammals), which is needed for autophagosome formation. In budding yeast, cortical and cytoplasmic ER-phagy requires the autophagy receptor Atg40. While different ER autophagy receptors have been identified, little is known about other components of the ER-phagy machinery. In an effort to identify these components, we screened the genome-wide library of viable yeast deletion mutants for defects in the degradation of cortical ER following treatment with rapamycin, a drug that mimics starvation. Among the mutants we identified was vps13Δ. While yeast has one gene that encodes the phospholipid transporter VPS13, humans have four vacuolar protein-sorting (VPS) protein 13 isoforms. Mutations in all four human isoforms have been linked to different neurological disorders, including Parkinson’s disease. Our findings have shown that Vps13 acts after Atg40 engages the autophagy machinery. Vps13 resides at contact sites between the ER and several organelles, including late endosomes. In the absence of Vps13, the cortical ER marker Rtn1 accumulated at late endosomes, and a dramatic decrease in ER packaging into autophagosomes was observed. Together, these studies suggest a role for Vps13 in the sequestration of the ER into autophagosomes at late endosomes. These observations may have important implications for understanding Parkinson’s and other neurological diseases.
Réhabilitation socio-économique d’une poule locale en voie d’extinction: la poule Kabyle (Thayazit lekvayel).

RESuME : Sous la pression du développement rapide de l’aviculture industrielle de par le monde, de nombreuses races locales de poules sont actuellement en voie d’extinction. or, dans les pays du Sud comme l’Algérie, les races locales constituent un outil important de développement rural et de lutte contre la pauvreté. De manière plus générale encore, la perte de toute biodiversité compromet notre aptitude à relever les défis écologiques et économiques futurs. Dans ce contexte, ce travail se propose de poser les bases d’une réhabilitation de la poule locale Kabyle, dont l’importance socioéconomique et culturelle est primordiale. cette étude décrit pour la première fois les caractéristiques morphobiométriques de la poule Kabyle et en évalue les aptitudes de croissance. La grande variabilité observée des caractères permet d'envisager d’importantes possibilités de sélection dans le but d’une amélioration de la productivité de l’élevage de volaille dans la région, basée sur les souches locales rustiques, particulièrement adaptées aux conditions d’élevage peu intensives qui y sont pratiquées. Seule cette double exigence de productivité et de rusticité permet en effet d’envisager l’élevage de volaille comme vecteur efficace de développement des activités économiques rurales en Algérie, pays caractérisé par la grande diversité de ses conditions pédoclimatiques.
Nosology Spectrum of the Bicuspid Aortic Valve Condition: Complex-Presentation Valvulo-Aortopathy.

Circulation. 2020;142:294–299. DOI: 10.1161/CIRCULATIONAHA.120. 046892 294 Hector I. Michelena , MD Saarwaani Vallabhajosyula, MBBS Siddharth K. Prakash, MD, PhD Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs Michelena and Prakash), who respond to the information and share their reasoning with the reader (regular type). A discussion by the authors follows.
The role of attention in retaining the binding of integral features in working memory

Previous studies have suggested that retaining bindings in working memory (WM) requires more object-based attention than retaining constituent features. However, we still need to address the object-based attention hypothesis to determine both the generality (Does the object-based attention hypothesis of binding apply to feature bindings other than those tested? ) and the reality (Was the observed effect in previous studies an artifact of the testing process? ). We addressed these two issues by focusing on the binding of integral features, which was ignored in previous studies. Integral features can be manipulated independently but cannot be attended to or processed independently of each other, and they are primarily perceived in a more unitary fashion. Consequently, integral-feature bindings should be processed as integrated units without the help of extra object-based attention. We examined whether or not the object-based attention hypothesis applied to integral-feature bindings (generality), and these results enabled us to check the reality of the hypothesis. In line with our prediction, we found that a secondary task consuming object-based attention did not selectively impair the binding performance (Experiments 1, 2, 3, 5, and 7). The absence of selective binding impairment was not attributable to the use of an invalid secondary task (Experiment 4), failure to memorize the binding between length and width (Experiment 6), tapping the incorrect type of attention (Experiment 6), the feasibility of feature categorization (Experiment 7), or poor task performance (Experiment 7). Overall, these results suggest that the object-based attention hypothesis does not fit for the integral-feature bindings, and that the pivotal role of object-based attention reported by previous studies was reliable.
Abstract GS4-07: Race, ethnicity and clinical outcomes in hormone receptor-positive, HER2-negative, node-negative breast cancer: results from the TAILORx trial

Background: Black race is associated with worse outcomes in localized hormone receptor (HR)-positive breast cancer in population-based and in clinical trial cohorts, whether using self-identified race (Albain et al. JNCI 2009 [PMID: 19584328; Sparano et al. JNCI 2012 [PMID: 22250182) or genetically-identified race (Schneider et al. J Precision Oncol 2017 [PMID: 29333527]). This disparity persists after adjustment for treatment delivery parameters (Hershman et al. JCO 2009 [PMID:19307504]). We evaluated clinicopathologic characteristics, treatment delivered and clinical outcomes in the Trial Assigning Individualized Options for Treatment (TAILORx) by race and ethnicity (Sparano et al. NEJM 2018 [PMID: 29860917]). Methods: The analysis included 9719 evaluable TAILORx participants. The association between clinical outcomes and race (white, black, Asian, other/unknown) and ethnicity (Hispanic vs. non-Hispanic) was examined, including invasive disease-free survival (iDFS), distant relapse-free interval (DRFI), relapse-free interval (RFI), and overall survival (OS). Proportional hazards models were fit including age (5 categories), tumor size (>2 cm vs. Results: The study population included 8189 (84%) whites, 693 (7%) blacks, 405 (4%) Asians, and 432 (4%) with other/unknown race. Regarding ethnicity, 7635 (79%) were non-Hispanic, 889 (9%) Hispanic, and 1195 (12%) unknown. There was no significant difference in RS distribution (p=0.22) in blacks compared with whites, or in median (17 vs. 17) or mean RS (19.1 vs. 18.2). There was likewise no difference in Hispanic vs. non-Hispanic ethnicity for RS distribution (p=0.72) or median (17 vs. 17) or mean RS (18.5 vs. 18.0). Black race (39% vs. 30%) and Hispanic ethnicity (39% vs. 30%) were both associated with younger age ( Conclusions: In patients eligible and selected for participation in TAILORx, black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy. This adds to an emerging body of evidence suggesting a biologic basis or other factors contributing to racial disparities in HR-positive breast cancer that requires further evaluation. Citation Format: Albain K, Gray RJ, Sparano JA, Makower DF, Pritchard KI, Hayes DF, Geyer, Jr. CE, Dees EC, Goetz MP, Olson, Jr. JA, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge, Jr. GW. Race, ethnicity and clinical outcomes in hormone receptor-positive, HER2-negative, node-negative breast cancer: results from the TAILORx trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-07.
Spatial scale and benthic community organisation in the littoral zones of large oligotrophic lakes: potential for cross‐scale interactions

Summary 1. We studied the spatial organisation of littoral, benthic invertebrate communities in two large oligotrophic lakes with very extensive heterogeneous littoral zones, and report that littoral communities show significant variation in their structure at multiple spatial scales. 2. At coarser scales, littoral zone topography, riparian inputs and exposure may be important drivers of community spatial structure. At finer scales, the composition of substrates, particularly macrophytes and inorganic sediments, may be drivers of community spatial structure. 3. The effects of substrates on community spatial patterns were non-additive across scales; community-habitat correspondence became very noisy when we attempted to extrapolate results throughout the littoral. We present some evidence to suggest that this non-additivity is because of the interaction among structuring processes that operate at different scales.
Genome-Wide Somatic Alterations in Multiple Myeloma Reveal a Superior Outcome Group

PURPOSE Multiple myeloma (MM) is accompanied by heterogeneous somatic alterations. The overall goal of this study was to describe the genomic landscape of myeloma using deep whole-genome sequencing (WGS) and develop a model that identifies patients with long survival. METHODS We analyzed deep WGS data from 183 newly diagnosed patients with MM treated with lenalidomide, bortezomib, and dexamethasone (RVD) alone or RVD + autologous stem cell transplant (ASCT) in the IFM/DFCI 2009 study (ClinicalTrials.gov identifier: NCT01191060). We integrated genomic markers with clinical data. RESULTS We report significant variability in mutational load and processes within MM subgroups. The timeline of observed activation of mutational processes provides the basis for 2 distinct models of acquisition of mutational changes detected at the time of diagnosis of myeloma. Virtually all MM subgroups have activated DNA repair–associated signature as a prominent late mutational process, whereas APOBEC signature targeting C>G is activated in the intermediate phase of disease progression in high-risk MM. Importantly, we identify a genomically defined MM subgroup (17% of newly diagnosed patients) with low DNA damage (low genomic scar score with chromosome 9 gain) and a superior outcome (100% overall survival at 69 months), which was validated in a large independent cohort. This subgroup allowed us to distinguish patients with low- and high-risk hyperdiploid MM and identify patients with prolongation of progression-free survival. Genomic characteristics of this subgroup included lower mutational load with significant contribution from age-related mutations as well as frequent NRAS mutation. Surprisingly, their overall survival was independent of International Staging System and minimal residual disease status. CONCLUSION This is a comprehensive study identifying genomic markers of a good-risk group with prolonged survival. Identification of this patient subgroup will affect future therapeutic algorithms and research planning.
Clinico-pathological correlations of macular lesions in leprosy, using a new histological grading system

In macular forms of pauci-bacillary (PB) leprosy as the dermal infiltrate is less, greater precision in evaluation is needed both for diagnosis, and for assessment of the efficacy of treatment. With this in view, a new numerical grading system on a scale from 0-4, with intervening decimals, was recently published to describe each specific pathology of the dermal nerves and appendages. This retrospective study of smear negative macular lesions, has utilized this grading system for comparison and follow up. Fifteen new patients with PB macular leprosy (TT, BT) were divided into two groups – Group A without deformity (ten patients), and Group B with deformity (five patients). All the patients had pre-treatment scalpel biopsies. In the pre-treatment biopsies in Group B the average grade of dermal granuloma was 1.3 compared to 0.5 in Group A. Two patients in Group A who were given daily Rifampicin and Dapsone for five and six months respectively, showed marked reduction in the infiltrate. In many biopsies a linear serpiginous infiltrate (horizontal) was present in the superficial dermis. This new grading system is useful for quantifying the dermal pathology in PB macular leprosy, for comparison of duration of treatment, or evaluation of newer drugs in studies, and for assessing resolution of the lesion by the pathologist. Keywords: Macular leprosy (PB), Histological grading, Dermal granuloma, Neural infiltrate and destruction, Linear serpiginous infiltrate.
Feeding behaviour and diet of dingoes in the Nullarbor region, Western Australia

Observations were made on the diet and feeding behaviour of the dingo (Canis familiaris dingo) in the Nullarbor region of Western Australia. Mammal species accounted for 96% of food items identified in diet samples. Rabbits (Oryctolagus cuniculus) and red kangaroos (Macropus rufus) were the most frequently occurring prey items. Cattle (Bos taurus) carrion, although available, was a relatively minor part of the diet. Foxes (Vulpes vulpes), cats (Felis catus), birds, reptiles and arthropods were eaten only occasionally. Dingoes usually hunted alone, and solitary dingoes were more successful in hunting rabbits than were members of groups. Only solitary dingoes were seen to chase and catch kangaroos, but kangaroo carcasses were often shared. We suggest that the widespread solitary foraging characteristic of dingoes on the Nullarbor may be related to their reliance on rabbits as the dietary staple.
Inhibition of Interleukin-1β-Induced COX-2 and EP3 Gene Expression by Sodium Salicylate Enhances Pancreatic Islet β-Cell Function

Previous work has suggested that functional interrelationships may exist between inhibition of insulin secretion by interleukin (IL)-1beta and the endogenous synthesis of prostaglandin E(2) (PGE(2)) in the pancreatic islet. These studies were performed to ascertain the relative abundance of E prostaglandin (EP) receptor mRNAs in tissues that are major targets, or major degradative sites, of insulin; to identify which EP receptor type mediates PGE(2) inhibition of insulin secretion in pancreatic islets; and to examine possible sites of action through which sodium salicylate might affect IL-1beta/PGE(2) interactions. Real-time fluorescence-based RT-PCR indicated that EP3 is the most abundant EP receptor type in islets, liver, kidney, and epididymal fat. EP3 mRNA is the least, whereas EP2 mRNA is the most, abundant type in skeletal muscle. Misoprostol, an EP3 agonist, inhibited glucose-induced insulin secretion from islets, an event that was prevented by preincubation with pertussis toxin, by decreasing cAMP. Electromobility shift assays demonstrated that sodium salicylate inhibits IL-1beta-induced nuclear factor-kappaB (NF-kappaB) activation. Sodium salicylate also prevented IL-1beta from inducing EP3 and cyclooxygenase (COX)-2 gene expression in islets and thereby prevented IL-1beta from inhibiting glucose-induced insulin secretion. These findings indicate that the sites of action through which sodium salicylate inhibits these negative effects of IL-1beta on beta-cell function include activation of NF-kappaB as well as generation of PGE(2) by COX-2.
Nutraceutical nanodelivery; an insight into the bioaccessibility/bioavailability of different bioactive compounds loaded within nanocarriers

Abstract Nanofoods is a current concept that is based on the application of nanotechnologies in the preparation of safe foods, with superior nutritional and sensory characteristics, and capable of providing multiple health benefits. In line with the principles of this concept, food scientists have focused on developing new types of nano biosystems that can contribute to increasing the bioavailability of bioactive compounds used in food fortification. Numerous research teams have investigated the main factors limiting oral bioavailability including: bioaccessibility, absorption and transformation of bioactive compounds and bioactive-loaded nanocarriers. The physicochemical processes involved in the factors limiting oral bioavailability have been extensively studied, such asthe release, solubility and interaction of bioactive compounds and nanocarriers during food digestion, transport mechanisms of bioactive compounds and nanoparticles through intestinal epithelial cells as well as the chemical and biochemical transformations in phase I and phase II reactions. In this comprehensive review, the physicochemical processes involved in the bioaccessibility/bioavailability of different encapsulated bioactive compounds, that play an important role in human health, will be explained including polyphenols, phytosterols, carotenoids, vitamins and minerals. In particular, the mechanisms involved in the cellular uptake of bioactive-loaded nanocarriers including transcellular transport (diffusion, endocytosis, pinocytosis, transcytosis, phagocytosis), paracellular transport (through the “tight junctions” between epithelial cells), and the active transport of bioactive compounds under the action of membrane transporters are highlighted.
Would they trust it? An exploration of psychosocial and environmental factors affecting prescriber acceptance of computerised dose‐recommendation software

Dose‐prediction software can optimise vancomycin therapy, improving therapeutic drug monitoring processes and reducing drug toxicity. Success of software in hospitals may be dependent on prescriber uptake of software recommendations. This study aimed to identify the perceived psychosocial and environmental barriers and facilitators to prescriber acceptance of dose‐prediction software.
Atmospheric nitrogen dioxide at ambient levels stimulates growth and development of horticultural plants

We recently discovered that atmospheric nitrogen dioxide (NO2) at ambient levels acts as a signal to Nicotiana plumbaginifolia Viviani, causing these plants to double both their biomass and all of the cell contents. Herein, we ad- dressed whether this effect of NO2 is also observed in various horticultural plants. Lettuce (Lactuca sativa L.), sunflower (Helianthus annuus L.), cucumber (Cucumis sativus L.), and pumpkin (Cucurbita moschata Duch. ex Lam.) were grown with 50, 200, 100, and 200 mLL -1 , respectively, of air supplemented with stable isotope-labelled ( 15 N) NO2, for 5-6 weeks. Control plants were grown without NO2 (<5 mLL -1 ). All plants were irrigated with nonlabelled nitrate. The presence of NO2 doubled both the aboveground and belowground biomass in sunflowers compared with their growth in the absence of NO2, whereas lettuce, cucumber, and pumpkin doubled in aboveground biomass only. Contents per shoot of carbon (C), nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) were almost doubled during the ''NO2- enhanced'' growth in lettuce, but not in other plants. Mass spectrometry analysis of 15 N/ 14 N indicated that only a minor proportion (0.2%-14%) of total plant N was derived from NO2, implying that exogenous NO2 acts as a signal rather than
Relationships between water-use traits and photosynthesis in Brassica oleracea resolved by quantitative genetic analysis

The genetic control of water-use and photosynthetic traits in Brassica oleracea is resolved by genetic analysis of quantitative trait loci (QTL). Variations in leaf conductance. photosynthetic assimilation rate. leaf thickness and leaf nitrogen content were assessed in a segregating population of F 1 -derived doubled haploid (DH) B. oleracea lines. In addition. stable carbon isotope ratios in leaf organic material were used as a surrogate measure of plant water-use efficiency. Analysis of an existing linkage map for the population revealed significant QTL on seven linkage groups. Single significant QTL. explained between 3.4% and 36.6% of the phenotypic variance in each of the trails measured. The locations of QTL for several traits were found to coincide in a physiologically meaningful way; stable carbon isotope discrimination had QTL co-locating with leaf level waler-use efficiency, pholosynthelic capacity with leaf thickness and nitrogen content and stomatal density with leaf thickness. Taken together. these results suggest that single genes or clusters of genes at these loci may have an influence on the expression of physiologically related trails controlling water-use and photosynthesis.
Caracterização morfológica de calos de Eucalyptus urophylla S. T. Blake sob concentrações de boro e cálcio

Objetivou-se avaliar o efeito de diferentes concentracoes de B e Ca nas respostas morfologicas e tamanho de calos de Eucalyptus urophylla, obtidos a partir da porcao mediana de hipocotilos excisados de plântulas germinadas in vitro. As estruturas calogenicas foram cultivadas por periodos de 21 e 31 dias, sendo mantidas no meio N7 modificado nas concentracoes de B (0, 25, 50, 100 e 200 µM de H3BO3) e Ca (0; 3,75; 7,5; 11,25 e 15 mM de CaCl2.2H2O). Os calos foram analisados quanto ao tamanho, presenca de raizes, friabilidade, aspecto gelatinoso, presenca de estruturas globulares na superficie e presenca de pigmentos. De maneira geral, o menor tempo de cultivo (21 dias) possibilitou melhor desenvolvimento das estruturas calogenicas. A combinacao de 50 µM de H3BO3 e 7,5 mM de CaCl2.2H2O aos 21 dias, e de 100 µM de H3BO3 e 1,13 mM CaCl2.2H2O aos 31 dias, promoveram os melhores resultados. A rizogenese respondeu de forma variavel as concentracoes de B e Ca. A omissao simultânea de B e Ca inibiu a rizogenese, causou a desestruturacao dos calos, e favoreceu a formacao de estruturas globulares e friaveis, com a ocorrencia de antocianina. Concentracoes elevadas de calcio promoveram a inducao de raizes nos calos.