bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin of electroneutrality in living system
Authors: Akbari Amir , Palsson Bernhard O. 
Published: September 2021

AbstractIdentifying the first chemical transformations, from which life emerged is a central problem in the theories of life’s origins. These reactions would likely have been self-sustaining and self-reproductive before the advent of complex biochemical pathways found in modern organisms to synthesize lipid membranes, enzymes, or nucleic acids. Without lipid membranes and enzymes, exceedingly low concentrations of the organic intermediates of early metabolic cycles in protocells would have significantly hindered evolvability. To address this problem, we propose a mechanism, where a positive membrane potential elevates the concentration of the organic intermediates. In this mechanism, positively charged surfaces of protocell membranes due to accumulation of transition metals generate positive membrane potentials. We compute steady-state ion distributions and determine their stability in a protocell model to identify the key factors constraining achievable membrane potentials. We find that (i) violation of electroneutrality is necessary to induce nonzero membrane potentials; (ii) strategies that generate larger membrane potentials can destabilize ion distributions; and (iii) violation of electroneutrality enhances osmotic pressure and diminishes reaction efficiency, thereby driving the evolution of lipid membranes, specialized ion channels, and active transport systems.SignificanceThe building blocks of life are constantly synthesized and broken down through concurrent cycles of chemical transformations. Tracing these reactions back 4 billion years to their origins has been a long-standing goal of evolutionary biology. The first metabolic cycles at the origin of life must have overcome several obstacles to spontaneously start and sustain their nonequilibrium states. Notably, maintaining the concentration of organic intermediates at high levels needed to support their continued operation and subsequent evolution would have been particularly challenging in primitive cells lacking evolutionarily tuned lipid membranes and enzymes. Here, we propose a mechanism, in which the concentration of organic intermediates could have been elevated to drive early metabolic cycles forward in primitive cells with ion-permeable porous membranes under prebiotic conditions and demonstrate its feasibility in a protocell model from first principles.
Single shot detector application for image disease localization
Authors: Chopade Rushikesh , Stanam Aditya , Pawar Shrikant 
Published: September 2021

AbstractBounding box algorithms are useful in localization of image patterns. Recently, utilization of convolutional neural networks on X-ray images has proven a promising disease prediction technique. However, pattern localization over prediction has always been a challenging task with inconsistent coordinates, sizes, resolution and capture positions of an image. Several model architectures like Fast R-CNN, Faster R-CNN, Histogram of Oriented Gradients (HOG), You only look once (YOLO), Region-based Convolutional Neural Networks (R-CNN), Region-based Fully Convolutional Networks (R-FCN), Single Shot Detector (SSD), etc. are used for object detection and localization in modern-day computer vision applications. SSD and region-based detectors like Fast R-CNN or Faster R-CNN are very similar in design and implementation, but SSD have shown to work efficiently with larger frames per second (FPS) and lower resolution images. In this article, we present a unique approach of SSD with a VGG-16 network as a backbone for feature detection of bounding box algorithm to predict the location of an anomaly within chest X-ray image.
Relative timing of RSV epidemics in summer 2021 across the US was similar to a typical RSV season
Authors: Zheng Zhe , Warren Joshua L. , Artin Iris , Pitzer Virginia E. , Weinberger Daniel M. 
Published: September 2021

AbstractWe evaluated the timing of respiratory syncytial virus (RSV) epidemics in 2021 using Google search data. Despite the unusual out-of-season timing, the relative timing of RSV epidemics between states in 2021 shared a similar spatial pattern with typical RSV seasons. These insights can inform prophylaxis administration and planning of clinical trials.
An artificial intelligence system for predicting mortality in COVID-19 patients using chest X-rays: a retrospective study
Authors: Nanivadekar Avinash , Zirpe Kapil , Dwivedi Ashutosh , Patel Rajan , Pant Richa , Gupte Tanveer , Lokwani Rohit , Shende Dinesh , Kulkarni Viraj , Kharat Amit 
Published: September 2021

ABSTRACTBackgroundEarly prediction of disease severity in COVID-19 patients is essential. Chest X-ray (CXR) is a faster, widely available, and less expensive imaging modality that may be useful in predicting mortality in COVID-19 patients. Artificial Intelligence (AI) may help expedite CXR reading times, and improve mortality prediction. We sought to develop and assess an artificial intelligence system that used chest X-rays and clinical parameters to predict mortality in COVID-19 patients.MethodsA retrospective study was conducted in Ruby Hall Clinic, Pune, India. The study included patients who had a positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for COVID-19 and at least one available chest X-ray at the time of their initial presentation or admission. Features from CXR images and clinical parameters were used to train the Random Forest model.ResultsClinical data from a total of 201 patients was assessed retrospectively. The average age of the cohort was 51.4±14.8 years, with 29.4% of the patients being over the age of 60. The model, which used CXRs and clinical parameters as inputs, had a sensitivity of 0.83 [95% CI: 0.7, 0.95] and a specificity of 0.7 [95% CI: 0.64, 0.77]. The area under the curve (AUC) on receiver operating characteristics (ROC) was increased from 0.74 [95% CI: 0.67, 0.8] to 0.79 [95% CI: 0.72, 0.85] when the model included features of CXRs in addition to clinical parameters.ConclusionAn Artificial Intelligence (AI) model based on CXRs and clinical parameters demonstrated high sensitivity and can be used as a rapid and reliable tool for COVID-19 mortality prediction.
Hyperconcentrated Mucus Unifies Submucosal Gland and Superficial Airway Dysfunction in Cystic Fibrosis
Authors: Kato Takafumi , Radicioni Giorgia , Papanikolas Micah J. , Stoychev Georgi V. , Markovetz Matthew R. , Aoki Kazuhiro , Porterfield Mindy , Okuda Kenichi , Barbosa Cardenas Selene M. , Gilmore Rodney C. , Morrison Cameron B. , Ehre Camille , Burns Kimberlie A. , White Kristen K. , Brennan Tara A. , Goodell Henry P. , Thacker Holly , Loznev Henry T. , Forsberg Lawrence J. , Nagase Takahide , Rubinstein Michael , Randell Scott H. , Tiemeyer Michael , Hill David B. , Kesimer Mehmet , O’Neal Wanda K. , Ballard Stephen T. , Freeman Ronit , Button Brian , Boucher Richard C. 
Published: September 2021

AbstractCystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway CF model revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Utilizing proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, proteomics analyses of CF sputum revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and within SMGs of the CF lung.
The impact of phosphorylated Pten at threonine 366 on cortical connectivity and behaviour
Authors: Ledderose Julia , Benitez Jorge A. , Roberts Amanda J. , Reed Rachel , Bintig Willem , Sachdev Robert , Furnari Frank , Eickholt Britta J. 
Published: September 2021

AbstractThe lipid phosphatase Pten (phosphatase and tensin homologue on chromosome 10) is a key tumour suppressor gene and an important regulator of neuronal signalling. Pten mutations have been identified in patients with autism spectrum disorders, characterized by macrocephaly, impaired social interactions and communication, repetitive behaviour, intellectual disability, and epilepsy. Pten enzymatic activity is regulated by a cluster of phosphorylation sites at the C-terminus of the protein. Here we specifically focussed on the role of Pten T366 phosphorylation and generated a knock-in mouse line in which Pten T366 was substituted with alanine (PtenT366A/T366A). We identify that phosphorylation of Pten at T366 controls neuron size and connectivity of brain circuits involved in sensory processing. We show in behavioural tests that PtenT366/T366A mice exhibit cognitive deficits and selective sensory impairments, with significant differences in male individuals. We identify restricted cellular overgrowth of cortical neurons in PtenT366A/T366A brains, linked to increases in both dendritic arborization and soma size. In a combinatorial approach of anterograde and retrograde monosynaptic tracing using rabies virus, we characterize differences in connectivity to the primary somatosensory cortex of PtenT366A/T366A brains, with imbalances in long-range cortico-cortical input to neurons. We conclude that phosphorylation of Pten at T366 controls neuron size and connectivity of brain circuits involved in sensory processing and propose that PTEN T366 signalling may account for a subset of autism-related functions of Pten.
Drivers of an epic radiation: the role of climate and islands in species diversification and reproductive-mode evolution of Old-World tree frogs
Authors: Ellepola Gajaba , Pie Marcio R. , Pethiyagoda Rohan , Hanken James , Meegaskumbura Madhava 
Published: September 2021

AbstractAlthough large diversifications of species occur unevenly across space and evolutionary lineages, the relative importance of their driving mechanisms, such as climate, ecological opportunity and key innovations, remains poorly understood. Here, we explore the remarkable diversification of rhacophorid frogs, which represent six percent of global amphibian diversity, utilize four distinct reproductive modes, and span a climatically variable area across mainland Asia, associated continental islands, and Africa. Using a complete species-level phylogeny, we find near-constant diversification rates but a highly uneven distribution of species richness. Montane regions on islands and some mainland regions have higher phylogenetic diversity and unique assemblages of taxa; we identify these as cool-wet refugia. Starting from a centre of origin, rhacophorids reached these distant refugia by adapting to new climatic conditions (‘niche evolution’-dominant), especially following the origin of key innovations such as terrestrial reproduction (in the Late Eocene) or by dispersal during periods of favourable climate (‘niche conservatism’-dominant).
Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids
Authors: Martino Michael R. , Gutiérrez-Aguilar Manuel , Yiew Nicole K.H. , Lutkewitte Andrew J. , Singer Jason M. , McCommis Kyle S. , Smith Gordon I. , Cho Kevin , Fletcher Justin A. , Klein Samuel , Patti Gary J. , Burgess Shawn C. , Finck Brian N. 
Published: September 2021

SUMMARYHepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We found that ALT2 was overexpressed in liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) was downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver was mediated by activating transcription factor 4; an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuated incorporation of 13C-alanine into newly synthesized glucose by hepatocytes. In vivo Gpt2 knockdown or knockout in liver had no effect on glucose concentrations in lean mice, but Gpt2 suppression alleviated hyperglycemia in db/db mice. These data suggest that ALT2 plays a significant role in hepatic gluconeogenesis from amino acids in diabetes.
Microbial Nanocellulose Biotextiles for a Circular Materials Economy
Authors: Schiros Theanne N. , Antrobus Romare , Farías Delfina , Chiu Yueh-Ting , Joseph Christian Tay , Esdaille Shanece , Sanchiricco Gwen Karen , Miquelon Grace , An Dong , Russell Sebastian T. , Chitu Adrian M. , Goetz Susanne , Chassé Anne Marika Verploegh , Nuckolls Colin , Kumar Sanat K. , Lu Helen H. 
Published: September 2021

AbstractThe synthesis and bottom-up assembly of nanocellulose by microbes offers unique advantages to tune and meet key design criteria—rapid renewability, low toxicity, scalability, performance, and degradability—for multi-functional, circular economy textiles. However, development of green processing methods that meet these criteria remains a major research challenge. Here, we harness microbial biofabrication of nanocellulose and draw inspiration from ancient textile techniques to engineer sustainable biotextiles with a circular life cycle. The unique molecular self-organization of microbial nanocellulose (MC) combined with bio-phosphorylation with a lecithin treatment yields a compostable material with superior mechanical and flame-retardant properties. Specifically, treatment of MC with a lecithin-phosphocholine emulsion makes sites available to modulate cellulose cross-linking through hydroxyl, phosphate and methylene groups, increasing the interaction between cellulose chains. The resultant bioleather exhibits enhanced tensile strength and high ductility. Bio-phosphorylation with lecithin also redirects the combustion pathway from levoglucosan production towards the formation of foaming char as an insulating oxygen barrier, for outstanding flame retardance. Controlled color modulation is demonstrated with natural dyes. Life cycle impact assessment reveals that MC bioleather has up to an order of magnitude lower carbon footprint than conventional textiles, and a thousandfold reduction in the carcinogenic impact of leather production. Eliminating the use of hazardous substances, these high performance materials disrupt linear production models and strategically eliminate its toxicity and negative climate impacts, with widespread application in fashion, interiors and construction. Importantly, the biotextile approach developed in this study demonstrates the potential of biofabrication coupled with green chemistry for a circular materials economy.
AMPK regulates germline stem cell integrity and quiescence through a mir-1/tbc-7/rab-7 pathway in C. elegans
Authors: Wong Christopher , Kadekar Pratik , Jurczak Elena , Roy Richard 
Published: September 2021

AbstractDuring periods of energetic stress, Caenorhabditis elegans can undergo a global quiescent stage known as “dauer”. During this stage, all germline stem cells undergo G2 cell cycle arrest through an AMPK-dependent mechanism. In animals that lack AMPK signalling, the germ cells fail to arrest, undergo uncontrolled proliferation and lose their reproductive capacity. These germline defects are accompanied by an altered chromatin landscape and gene expression program. We identified an allele of tbc-7, a RabGAP protein that functions in the neurons, which when compromised, suppresses the germline hyperplasia in the dauer larvae, as well as the post-dauer sterility and somatic defects characteristic of AMPK mutants. This mutation also corrects the abundance and aberrant distribution of transcriptionally activating and repressive chromatin marks in animals that otherwise lack all AMPK signalling. We identified RAB-7 as one of the potential RAB proteins that is regulated by tbc-7 and show that the activity of RAB-7 is critical for the maintenance of germ cell integrity during the dauer stage. A singular small RNA, mir-1, was identified as a direct negative regulator of tbc-7 expression through the analysis of seed sequences on the 3’UTR of tbc-7. Animals lacking mir-1 are post-dauer sterile, displaying a similar phenotype to AMPK mutants. Altogether, our findings describe a novel mir-1/tbc-7/rab-7 pathway occurring in the neurons that regulates the germ line in a cell non-autonomous manner.
pSNAP: Proteome-wide analysis of elongating nascent polypeptide chains
Authors: Uchiyama Junki , Roy Rohini , Wang Dan Ohtan , Morikawa Kazuya , Kawahara Yuka , Iwasaki Mio , Yoshino Chiaki , Mishima Yuichiro , Ishihama Yasushi , Imami Koshi 
Published: September 2021

SummaryCellular global translation is often measured using ribosome profiling or quantitative mass spectrometry, but these methods do not provide direct information at the level of elongating nascent polypeptide chains (NPCs) and associated co-translational events. Here we describe pSNAP, a method for proteome-wide profiling of NPCs by affinity enrichment of puromycin- and stable isotope-labeled polypeptides. pSNAP does not require ribosome purification and/or chemical labeling, and captures bona fide NPCs that characteristically exhibit protein N-terminus-biased positions. We applied pSNAP to evaluate the effect of silmitasertib, a potential molecular therapy for cancer, and revealed acute translational repression through casein kinase II and mTOR pathways. We also characterized modifications on NPCs and demonstrated that the combination of different types of modifications, such as acetylation and phosphorylation in the N-terminal region of histone H1.5, can modulate interactions with ribosome-associated factors. Thus, pSNAP provides a framework for dissecting co-translational regulations on a proteome-wide scale.
LON DELETION IMPAIRS PERSISTER CELL RESUSCITATION IN ESCHERICHIA COLI
Authors: Mohiuddin Sayed Golam , Massahi Aslan , Orman Mehmet A. 
Published: September 2021

ABSTRACTBacterial persisters are non-growing cells that are highly tolerant to bactericidal antibiotics. However, this tolerance is reversible and not mediated by heritable genetic changes. Lon, an ATP-dependent protease, has repeatedly been shown to play a critical role in fluoroquinolone persistence. Although lon deletion (Δlon) is thought to kill persister cells via accumulation of the cell division inhibitor protein SulA, the exact mechanism underlying this phenomenon has yet to be elucidated. Here, we show that Lon is an important regulatory protein for the resuscitation of the fluoroquinolone persisters in Escherichia coli, and lon deletion impairs the ability of persister cells to form colonies during recovery, without killing these cells, through a sulA- and ftsZ-dependent mechanism. Notably, this observed non-culturable state of antibiotic-tolerant Δlon cells is transient, as environmental conditions, such as starvation, can restore their culturability. Our data further indicate that starvation-induced SulA degradation or expression of Lon during recovery facilitates Z-ring formation in Δlon persisters. Calculating the ratio of the cell length (L in µm) to the number of Z-rings (Z) for each ofloxacin-treated intact cell analyzed has revealed a strong correlation between persister resuscitation and calculated L/Z values, which represents a potential biomarker for Δlon persisters that are transitioning to the normal cell state under the conditions studied here.
Anti-PF4 VITT antibodies are oligoclonal and variably inhibited by heparin
Authors: Singh B , Kanack A , Bayas A , George G , Abou-Ismail MY , Kohlhagen M , Christ M , Naumann M , Moser K , Smock K , Grazioli A , Murray D , Padmanabhan A 
Published: September 2021

AbstractBackgroundCOVID-19 vaccines have been associated with a rare thrombotic and thrombocytopenic reaction, Vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by platelet-activating anti-PF4 antibodies. This study sought to assess clonality of VITT antibodies and evaluate their characteristics in antigen-based and functional platelet studies.MethodsAnti-PF4 antibodies were isolated from five patients with VITT secondary to ChAdOx1 nCoV-19 (n=1) or Ad26.COV2.S (n=4) vaccination. For comparative studies with heparin-induced thrombocytopenia (HIT), anti-PF4 antibodies were isolated from one patient with spontaneous HIT, another with “classical” HIT, and two patients with non-pathogenic (non-platelet activating) anti-PF4 antibodies. Isolated antibodies were subject to ELISA and functional testing, and mass spectrometric evaluation for clonality determination.ResultsAll five VITT patients had oligoclonal anti-PF4 antibodies (3 monoclonal, one bi- and one tri-clonal antibodies), while HIT anti-PF4 antibodies were polyclonal. Notably, like VITT antibodies, anti-PF4 antibodies from a spontaneous HIT patient were monoclonal. The techniques employed did not detect non-pathogenic anti-PF4 antibodies. The ChAdOx1 nCoV-19-associated VITT patient made an excellent recovery with heparin treatment. In vitro studies demonstrated strong inhibition of VITT antibody-induced platelet activation with therapeutic concentrations of heparin in this and one Ad26.COV2.S-associated VITT patient. Oligoclonal VITT antibodies with persistent platelet-activating potential were detected at 6 and 10 weeks after acute presentation in two patients tested. Two of the 5 VITT patients had recurrence of thrombocytopenia and one patient had focal seizures several weeks after acute presentation.ConclusionOligoclonal anti-PF4 antibodies mediate VITT. Heparin use in VITT needs to be further studied.