Miracle-dz/UniFAR-FTUs huggingface dataset:
Leishmania infection triggers hepcidin-mediated proteasomal degradation of Nramp1 resulting in increased phagolysosomal iron availability

Natural resistance associated macrophage protein 1 (Nramp1) was discovered as a genetic determinant of resistance against multiple intracellular pathogens, including Leishmania. It encodes a transmembrane protein of the phago-endosomal vesicles, where it functions as an iron transporter. But how Nramp1 expression is regulated in an infected macrophage is unknown. Its role in controlling iron availability to the intracellular pathogens and in determining the final outcome of an infection also remains to be fully deciphered. Here we report that Nramp1 protein abundance undergoes temporal changes in Leishmania major infected macrophages. At 12 hours post infection, there was drastic lowering of Nramp1 level accompanied by increased phagolysosomal iron availability and enhanced parasite growth. Leishmania infection-induced downregulation of Nramp1 was found to be caused by ubiquitin-proteasome degradation pathway. In fact, blocking of Nramp1 degradation with proteasome inhibitor resulted in depletion of phagolysosomal iron pool with significant reduction in the number of intracellular parasites. Further, we uncovered that this degradation process is mediated by the iron regulatory peptide hormone hepcidin that binds to Nramp1. Interestingly, Nramp1 protein level was restored to normalcy after 30 hours of infection with a concomitant drop in the phagolysosomal iron level, which is suggestive of a host counter defense strategy to deprive the pathogen of this essential micronutrient. Taken together, our study implicates Nramp1 as a central player in the host-pathogen battle for iron. It also unravels Nramp1 as a novel partner for hepcidin. The hitherto unidentified ‘hepcidin-Nramp1 axis’ may have a broader role in regulating macrophage iron homeostasis. Importance Leishmania parasites are the causative agents of a group of neglected tropical diseases called leishmaniasis. They reside within the phagolysosomes of mammalian macrophages. Since iron is an essential micronutrient for survival and virulence, intracellular Leishmania must acquire it from the tightly regulated macrophage iron pool. How this challenging task is accomplished remains a fundamental question in Leishmania biology. We report here that Leishmania major infection caused ubiquitin-proteasome-mediated degradation of natural resistance associated macrophage protein 1 (Nramp1). Nramp1 being an iron exporter at the phago-endosomal membrane, its degradation resulted in increased phagolysosomal iron availability thereby stimulating parasite growth. We also uncovered that Nramp1 degradation is controlled by the iron regulatory peptide hormone hepcidin. Interestingly, at a later stage of infection, Nramp1 protein level was restored to normalcy with simultaneous depletion of phagolysosomal iron. Collectively, our study implicates Nramp1 as a central player in the host-pathogen struggle for acquiring iron.
Ensemble cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation

Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. The enzyme is heavily regulated to maintain balance between guanine and adenine nucleotide pools. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand, providing an additional layer of regulatory control associated with increased flux through the guanine synthesis pathway. Here, we report a series of human IMPDH2 cryo-EM structures in active and inactive conformations, and show that the filament resists inhibition by guanine nucleotides. The structures define the mechanism of filament assembly, and reveal how assembly interactions tune the response to guanine inhibition. Filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions, like stem cell proliferation and T-cell activation, that require expansion of guanine nucleotide pools.
Health in the U.S. at Young Ages: Preliminary Findings

We review a broad set of health-related indicators—mortality, health outcomes, proximate health determinants, and distal health determinants—for the US and a comparison group of peer OECD countries. The principal findings are: (a) the US ranks consistently worse than peer countries on all but a few indicators; and (b) there is a strong relationship between the US health rankings across the life cycle: performance at one stage predicts performance in subsequent stages. We are supported by core grants to the Center for Demography and Ecology, University of Wisconsin (R24 HD047873) and to the Center for Demography of Health and Aging, University of Wisconsin (P30 AG017266); student training support is provided by both an NICHD Training Grant (T32 HD07014) and an NIA Training Grant (T32 AG00129). We are also thankful for partial support from the National Research Council and for comments to earlier versions of this paper from all members of the National Research Council panel on Understanding Cross-National Health Differences Among High-Income Countries.
Energy levels in multiple supplements for finishing beef cattle grazing palisade grass pasture during the rainy to dry transition season

The effects of energy levels in multiple supplements on productive performance and nutritional parameters were evaluated of finishing beef cattle grazing palisade grass (Brachiaria brizantha cv. Marandu), during the rainy to dry transition season. For the performance evaluation, 24 crossbred bulls, 18 month old and 330 kg of initial body weight (BW), were distributed to a completely randomized design, in four paddocks of 1.5 ha each. Four treatments were evaluated: mineral mix (MM) and corn and whole soybean grain based [. ]
Ultrasonographic Evaluation of Involuting Reproductive Tract in Postpartum Kankrej cows

The study was intended to evaluate echogenicity of post-partum reproductive tract in Kankrej cows. The real-time B-mode ultrasonography of post partum reproductive tract i.e. cervix, uterus, caruncle and middle uterine artery revealed images of different echogenicity in Kankrej cows. The images of involuting cervix were recorded as a bright hyperechoic wall and hypoechoic lumen with bright hyperechoic spots. The uterine images showed hyperechoic wall and anechoic lumen with hypoechoic spot. The caruncles had bright hyperechoic image with encircled anechoic line, While, middle uterine artery showed anechoic image.
DIAGNOSTIC AND THERAPEUTIC AND DIFFICULTIES IN A CASE OF TUBERCULOUS EMPYEMA WITH ATYPICAL MYCOBACTERIA

We report a 48 years old patient who developed a residual cavity with empyema after a decortication performed in another unit 1,5 years ago, which had been treated with repeated thoracenthesis, tube thoracostomies and antibiotic treatments. All the bacteriologic probes were negative for tuberculosis but pathologic examination of pleural deposits removed during decortication was not performed. We performed an one-stage thoracopleuroplasty on 7 ribs, Botianu personal procedure. Postoperative course was initially favourable, followed by development of a residual cavity with a volume reduced to half of the initial one, which was treated by a modified Eloesser open-window procedure. Pathologic examination of pleural deposits showed specific inflammation which explains the unfavourable evolution in the absence of a tuberculostatic treatment. Healing was achieved by daily dressings and full antituberculous treatment. Pathologic examination of pleural deposits removed during surgery is mandatory since it may diagnose specific inflammation and change the treatment and outcome. Absence of a correct etiologic diagnosis and treatment explains failure of multiple procedures requiring an open-window for the local control of infection. KEY-WORDS: TUBERCULOSIS EMPYEMA, ATYPICAL MYCOBACTERIA, OPEN WINDOW Correspondence: Petre V.H. Boţianu; 4-th Surgical Clinic, University of Medicine and Pharmacy Târgu-Mures, România; 540139, Gheorghe Marinescu Street 66/1; e-mail: botianu_petre@yahoo.com
To their own beat: modelling variability in induced pluripotent stem cell‐derived cardiomyocytes

The potential of human induced pluripotent stem cell-derived cardiomyocytes (iPSCCMs) to revolutionize cardiac research has spurred researchers into action. With their unique genetic backgrounds, patientderived iPSC-CMs are ideal for developing disease models, studying genotype– phenotype relationships and investigating patient-specific responses. In an age in which the frontier of personalized medicine seems more attainable than ever, iPSC-CM technology provides an unprecedented opportunity to advance areas like regenerative medicine, disease modelling and toxicity screening (Bruyneel et al. 2018). Despite this promise, the iPSC-CM field faces two major issues: large variability and immature physiology. Diversity is at the core of iPSC-CMs. This is desirable, considering the variety of genetic profiles of different iPSC lines that can be studied, while also challenging, as iPSC-CMs differentiated with protocols from various laboratories exhibit variable behaviours. It is impossible to pinpoint a uniform behaviour as normal, since ‘normal’ physiology for iPSC-CMs spans a wide range. Current techniques have also struggled to differentiate iPSC-CMs beyond the level of maturity seen in embryonic cardiomyocytes. As a result, iPSC-CMs display characteristics that are not seen in adult myocytes such as spontaneous beating, depolarized resting potential and lack of defined sarcomeres. In 2013, Paci et al. described the first computational model of iPSC-CM electrophysiology (Paci et al. 2013). Although the scarcity of experimental data limited the complexity of certain current formulations, for some time the Paci et al. model remained the only one available for this cell type. In the following years, several alternative models informed by more sophisticated cellular data and with improved representation of calcium handling were developed. The most recent advance has come in an article in The Journal of Physiology by Kernik et al. (2019) who built a thoroughly informed model using an array of data sources. In a groundbreaking step forward, this model comprehensively captures the variability inherent in iPSC-CMs. Furthermore, using model populations to represent experimentally observed behavioural heterogeneity enabled a wide range of cellular behaviours to be systematically dissected and understood through the variability of single channels. This approach, using rich datasets and populations of models to encompass the full diversity of possible iPSC-CM behaviour, represents remarkable progress towards facilitating the analytical utility of iPSC-CMs in high throughput screening and in uncovering patient-specific insights on disease mechanisms and therapeutic interventions. Below, we summarize notable results from the recent publication of Kernik et al.’s model and discuss its implications for the iPSC-CM field.
SMART: Statistical Mitogenome Assembly with Repeats

By using next-generation sequencing technologies it is possible to quickly and inexpensively generate large numbers of relatively short reads from both the nuclear and mitochondrial DNA contained in a biological sample. Unfortunately, assembling such whole-genome sequencing (WGS) data with standard de novo assemblers often fails to generate high quality mitochondrial genome sequences due to the large difference in copy number (and hence sequencing depth) between the mitochondrial and nuclear genomes. Assembly of complete mitochondrial genome sequences is further complicated by the fact that many de novo assemblers are not designed for circular genomes, and by the presence of repeats in the mitochondrial genomes of some species. In this paper we describe the Statistical Mitogenome Assembly with Repeats (SMART) pipeline for automated assembly of complete circular mitochondrial genomes from WGS data. SMART uses an efficient coverage-based filter to first select a subset of reads enriched in mtDNA sequences. Contigs produced by an initial assembly step are filtered using BLAST searches against a comprehensive mitochondrial genome database, and used as “baits” for an alignment-based filter that produces the set of reads used in a second de novo assembly and scaffolding step. In the presence of repeats, the possible paths through the assembly graph are evaluated using a maximum-likelihood model. Additionally, the assembly process is repeated a user-specified number of times on re-sampled subsets of reads to select for annotation the reconstructed sequences with highest bootstrap support. Experiments on WGS datasets from a variety of species show that the SMART pipeline produces complete circular mitochondrial genome sequences with a higher success rate than current state-of-the art tools, even from low coverage WGS data. The pipeline is available through an easy-to-use web interface at https://neo.engr. uconn.edu/? tool_id=SMART.
RNA polymerase I passage through nucleosomes depends on its lobe binding subunits

RNA polymerase I (Pol I) is a highly efficient enzyme specialized to synthesize most of the ribosomal RNA. After nucleosome deposition at each round of replication the Pol I transcription machinery has to deal with nucleosomal barriers. It was suggested that Pol I-associated factors facilitate chromatin transcription, but it is not known whether Pol I has an intrinsic capacity to transcribe through nucleosomes. Here we used in vitro transcription assays to study purified Pol I of the yeast S. cerevisiae and Pol I mutants in comparison to Pol II and Pol III to pass a nucleosome. Under identical conditions, purified Pol I and Pol III, but not Pol II, were able to transcribe nucleosomal templates. Pol I mutants lacking either the heterodimeric subunit Rpa34.5/Rpa49 or the C-terminal part of the specific subunit Rpa12.2 showed a lower processivity on naked DNA templates, which was even more reduced in the presence of a nucleosome. The contribution of Pol I specific subunit domains to efficient passage through nucleosomes in context with transcription rate and processivity is discussed.
Characterization of Lipid Phosphate Phosphatase Genes and in Planta Expressed Orphan Genes in the Rice Blast Fungus

Considering the implication of diacylglycerol (DAG) in both metabolism and signaling pathways, maintaining proper levels of DAG is critical to cellular homeostasis and development in fungi. Except the PIP2-PLC mediated pathway, metabolic pathways leading to generation of DAG converge on dephosphorylation of phosphatidic acid catalyzed by lipid phosphate phosphatases (LPP). To understand the role of LPPs in fungal development and pathogenicity, five genes encoding putative LPPs (MoLPP1 to MoLPP5) were identified and analyzed in a model plant pathogenic fungus, Magnaporthe oryzae. Expression analysis using qRT-PCR showed the
Disease classification in Solanum melongena using deep learning

Aim of study: The application of pre-trained deep learning models, AlexNet and VGG16, for classification of five diseases (Epilachna beetle infestation, little leaf, Cercospora leaf spot, two-spotted spider mite and Tobacco Mosaic Virus (TMV)) and a healthy plant in Solanum melongena (brinjal in Asia, eggplant in USA and aubergine in UK) with images acquired from smartphones.Area of study: Images were acquired from fields located at Alangudi (Pudukkottai district), Tirumalaisamudram and Pillayarpatti (Thanjavur district) – Tamil Nadu, India.Material and methods: Most of earlier studies have been carried out with images of isolated leaf samples, whereas in this work the whole or part of the plant images were utilized for the dataset creation. Augmentation techniques were applied to the manually segmented images for increasing the dataset size. The classification capability of deep learning models was analysed before and after augmentation. A fully connected layer was added to the architecture and evaluated for its performance.Main results: The modified architecture of VGG16 trained with the augmented dataset resulted in an average validation accuracy of 96.7%. Despite the best accuracy, all the models were tested with sample images from the field and the modified VGG16 resulted in an accuracy of 93.33%. Research highlights: The findings provide a guidance for possible factors to be considered in future research relevant to the dataset creation and methodology for efficient prediction using deep learning models.
PREPREGNANCY BODY MASS INDEX AND PREGNANCY WEIGHT GAIN IN RURAL REGIONS OF GUILAN PROVINCE, IRAN

Maternal nutritional status and weight gain throughout pregnancy affect the outcome of pregnancy. The objective of this study was to determine prepregnancy body mass index and total weight gain during pregnancy in women from rural areas of Guilan province, Iran. Prenatal and obstetrical records of 480 pregnant women who attended rural health centers between 2002 and 2003 including prepregnancy weights and pregnancy weight gains were analyzed. Prevalence of prepregnancy underweight and obesity was 7.9% and 27.3%, respectively. Total pregnancy weight gain was 9.3±4.1 kg. More than 40% of women did not meet the international recommendation regarding weight gain for their prepregnancy body mass index. Maternal height and body mass index were related to low birth weight. More than one third of women in rural areas of Guilan province did not meet the international recommendation regarding pregnancy weight gain. The inclusion of nutritional education in the existing health education programs in local health centers of the Province would be of value in meeting the international recommendation regarding weight gain during pregnancy. Iran J Med Sci 2007; 32(1): 36-39.
Multicomponent analysis and activities for evaluation of Dioscorea oppositifolia and Dioscorea hamiltonii

ABSTRACT Dioscorea oppositifolia (Chinese yam) (DO) and Dioscorea hamiltonii (DH) are the plants of the genus Dioscorea and they are used as health food and traditional Chinese medicine. In order to development of the available DO and DH source, a comparative study of principal components and activities were carried on. DO and DH was qualitatively and quantitively profiled, and we comparatively evaluated their antioxidant (reducing power assay), anti-inflammatory (xylene-induced ear oedema test) and nonspecific immune regulating (carbon clearance test) activities. The 42 and 38 compounds were detected from DO and DH by the method UPLC-DAD-Q-TOF-MS/MS, respectively, as well as 14 compounds are quantified by HPLC and the methodology was examined. This is the first study of the composition and activities of DH, it also indicates that DO and DH consumption would be beneficial to the health. They may be useful in the production of functional food containing an efficacious dose.
Emerging topics in scientific research on global water-use efficiency

Abstract A bibliometric analysis of research articles published on water-use efficiency was performed using the Web of Science database and evaluated. Journal titles, publication years, subject categories, keywords and countries publishing were obtained. A number of 2077 papers were retrieved, two-thirds of them published in the last decade. The articles were published in 439 journals, with Agricultural Water Management, Agronomy Journal, Crop Science, Field Crops Research and Indian Journal of Agricultural Sciences the most productive. Most of the leading productive journals have Impact Factors in the top quartiles of the Journal Citation Reports. Agronomy, Plant Sciences, Water Resources and Agriculture Multidisciplinary were the most common journal subject categories, indicating a wide diversity of research fields ascribed to this topic. The predominant key words and phrases used were growth, ‘carbon isotope discrimination’, yield, photosynthesis, ‘gas exchange’, evapotranspiration and ‘stomatal conductance’. The productivity ranking for countries was headed by China (456 papers), followed by the USA (410), Australia (176) and India (165). A content analysis of the papers made identification of the key issues of greatest scientific concern possible, as well as their evolution over time. The most cited papers relate to physiological aspects, but also important studies on experimental biology, drought resistance, effects of climate, crop production and ecology, among others.
Neutrophil gelatinase-associated lipocalin as a potential biomarker for pulmonary thromboembolism

Abstract Objective Pulmonary thromboembolism (PTE) is a clinical condition that can be lethal unless promptly diagnosed and treated. The objective was to evaluate the significance of serum neutrophil gelatinase-associated lipocalin (NGAL) in the diagnosis of PTE. Materials and methods In this study, 60 patients hospitalized for acute PTE between May 2015 and December 2016 were enrolled. PTE was diagnosed using spiral computed tomography angiography of the thorax. Cardiac enzyme levels, arterial blood gas, and echocardiography measurements were performed. Whole blood samples were drawn to measure serum NGAL before treatment. Results The PTE group comprised 34 women and 26 men, and the healthy control group included 22 women and 18 men. The mean ages of the patient and control groups were 70.3 ± 14.4 years and 69.0 ± 10.2 years, respectively. Serum NGAL was significantly higher in the patients than in the controls (88.6 ± 33.6 vs. 31.7 ± 10.0 ng/mL, p < 0.001, respectively). The optimal NGAL cut-off value was >50 ng/mL, the sensitivity was 100%, specificity was 98.3%, the negative predictive value was 100%, and the positive predictive value was 68%. Conclusion Serum NGAL is a new biomarker with high sensitivity and specificity to detect, diagnose, and exclude PTE.
Implementing an Integrated Electronic Discharge Summaries Solution to Improve Hospital Communication with General Practitioners

The growing acuity of hospital patients coupled with shorter hospitalisations imply an increasing need to ensure effective communication between hospital staff and general practitioners. This paper will describe the rapid implementation of a fully integrated clinical information system designed to improve the communication of discharge information between a metropolitan health service (Peninsula Health, Victoria) and general practitioners. The system uses browser-based technology (Concerto , Orion Systems International) to integrate multiple hospital information systems, connecting them to provide clinicians with a seamless 'single patient view'. The electronic discharge summary (EDS) component provides discharging clinicians with an easy to use, largely 'point and click' method of formulating discharge summaries. Upon discharge, the electronic document is transmitted to the general practitioner's surgery via either auto fax or directly to their desktop PC via a secure network (HealthLink.Net). The system has recently been successfully implemented and is now demonstrating qualitative and quantitative improvements in Peninsula Health's discharge documentation.