bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlled Oxygenated Rewarming Compensates for Cold Storage–induced Dysfunction in Kidney Grafts
Authors: von Horn Charlotte , Zlatev Hristo , Kaths Moritz , Paul Andreas , Minor Thomas 
Published: June 2021

Background.
Normothermic machine perfusion (NMP) provides a promising strategy for preservation and conditioning of marginal organ grafts. However, at present, high logistic effort limits normothermic renal perfusion to a short, postponed machine perfusion at site of the recipient transplant center. Thus, organ preservation during transportation still takes place under hypothermic conditions, leading to significantly reduced efficacy of NMP. Recently, it was shown that gentle and controlled warming up of cold stored kidneys compensates for hypothermic induced damage in comparison to end ischemic NMP. This study aims to compare controlled oxygenated rewarming (COR) with continuous upfront normothermic perfusion in a porcine model of transplantation.

Methods.
Following exposure to 30 min of warm ischemia, kidneys (n = 6/group) were removed and either cold stored for 8 h (cold storage [CS]), cold stored for 6 h with subsequent controlled rewarming up to 35 °C for 2 h (COR), or directly subjected to 8 h of continuous NMP. Kidney function was evaluated using a preclinical autotransplant model with follow-up for 7 d.

Results.
NMP and COR both improved renal function in comparison to CS and displayed similar serum creatinine and urea levels during follow-up. COR resulted in less tenascin C expression in the tissue compared with CS, indicating reduced proinflammatory upregulation in the graft by gentle rewarming.

Conclusions.
COR seems to be a potential alternative in clinical application of NMP, thereby providing logistic ease and usability.
Comparative study of the reorganization in bilateral motor and sensory cortices after spinal cord hemisection in mice
Authors: Deng Junhao , Xie Huimin , Chen Youbai , Peng Zhan , Zhao Jiajia , Zhou Yanmei , Chen Chao , Zhang Kexue 
Published: June 2021

Objective
The effects of spinal cord injury (SCI) on sensorimotor cortex plasticity have not been well studied. Therefore, to explore the reorganization after SCI, we dynamically monitored postsynaptic dendritic spines of pyramidal neurons in vivo.

Methods
Thy1-YFP transgenic mice were randomly divided into two groups: the control and SCI group. We then opened the spinal vertebral plates of all mice and sectioned one-half of the spinal cord in SCI group. The relevant areas were imaged bilaterally at 0, 3, 14 and 28 days post-SCI. The rates of elimination, formation and stable spines were evaluated.

Results
At the early stage, the rate of stable and elimination spines experienced a similar change trend. But the rate of formation spines in the contralateral sensory cortex was significantly increased after SCI compared with those in the control group. At the late stage, spines of three types remodeled very differently between the sensory and motor cortex. Compared with those in the control group, spines in the bilateral sensory cortex demonstrated obvious differences in the rate of stable and elimination spines but not formation spines, while spines in the motor cortex, especially in the contralateral cortex increased significantly in the rate of formation after SCI. As for survival rate, differences mainly appeared in time frame instead of cortex type or region.

Conclusions
The dendritic spines in hindlimb representation area of the sensorimotor cortex experienced bilaterally remodeling after SCI. And those spines in the sensory and motor cortex experienced great but different change trends after SCI.
SLIMP: Supervised learning of metabolite-protein interactions from co-fractionation mass spectrometry data
Authors: Zühlke Boris M. , Sokolowska Ewelina M. , Luzarowski Marcin , Schlossarek Dennis , Chodasiewicz Monika , Leniak Ewa , Skirycz Aleksandra , Nikoloski Zoran 
Published: June 2021

AbstractMetabolite-protein interactions affect and shape diverse cellular processes. Yet, despite advances, approaches for identifying metabolite-protein interactions at a genome-wide scale are lacking. Here we present an approach termed SLIMP that predicts metabolite-protein interactions using supervised machine learning on features engineered from metabolic and proteomic profiles from a co-fractionation mass spectrometry-based technique. By applying SLIMP with gold standards, assembled from public databases, along with metabolic and proteomic data sets from multiple conditions and growth stages we predicted over 9,000 and 20,000 metabolite-protein interactions forSaccharomyces cerevisiaeandArabidopsis thaliana, respectively. Extensive comparative analyses corroborated the quality of the predictions from SLIMP with respect to widely-used performance measures (e.g. F1-score exceeding 0.8). SLIMP predicted novel targets of 2’, 3’ cyclic nucleotides and dipeptides, which we analysed comparatively between the two organisms. Finally, predicted interactions for the dipeptide Tyr-Asp in Arabidopsis and the dipeptide Ser-Leu in yeast were independently validated, opening the possibility for future applications of supervised machine learning approaches in this area of systems biology.
Clinical profile and immediate outcome of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Covid-19: a multicentric study
Authors: Sethy Geetanjali , Mishra Bibhudatta , Jain Mukesh Kumar , Patnaik Sibabratta , Mishra Reshmi , Behera Jyoti Ranjan , Sahoo Bandya 
Published: June 2021

STRUCTURED ABSTRACTINTRODUCTIONFollowing an asymptomatic or mildly symptomatic Corona virus disease (COVID 19), otherwise healthy children, may develop serious manifestations in form of cardiac, neurological, respiratory, gastrointestinal and dermatologic dysfunction. Many such cases were being observed in Odisha, an eastern state of India and reported from different health care facilities. We related these unexplained serious manifestations to Multisystem Inflammatory Syndrome associated with COVID 19 (MIS-C) and planned this study.METHODSThis retrospective observational study was carried out in three tertiary care centres: Kalinga Institute of Medical Sciences, Bhubaneswar, MKCG Medical college Berhampur and Jagannath Hospital, Bhubaneswar between July to September of year 2020. Study population include all children from 1 month to 15 years admitted to hospital with MIS-C according to WHO Diagnostic Criteria. All the data were analyzed by SPSS.RESULTSA total of 21 children were included in our study. Maximum number of cases were male (76.2%), predominate age group was 6-10 yrs (47.6%). Predominate symptoms /signs in our observation were fever, pain abdomen, seizure and hypotension. Most of these cases were positive for SARS CoV antibody (80.95%). Response to immunotherapy was dramatic. Mortality (9%) of our study is higher to 1.8–3% from western literature. None of our patient had coronary abnormality while 2 had mild cardiac dysfunction at discharge comparable to other studies.CONCLUSIONMIS-C following exposure to COVID 19 infection in children is a clinical syndrome which needs early suspicion and appropriate intervention to prevent mortality.
In vivo delayed clearance of Plasmodium falciparum malaria independent of kelch13 polymorphisms and with escalating malaria in Bangladesh
Authors: Nima Maisha Khair , Sazed Saiful Arefeen , Mukherjee Angana , Hossainey Muhammad Riadul Haque , Phru Ching Swe , Johora Fatema Tuj , Safeukui Innocent , Saha Anjan , Khan Afsana Alamgir , Prue Marma Aung Swi , Ware Russell E. , Narla Mohandas , Calhoun Barbara , Haque Rashidul , Khan Wasif Ali , Alam Mohammad Shafiul , Haldar Kasturi 
Published: June 2021

AbstractThe emergence of resistance to artemisinin drugs threatens global malaria control. Resistance is widely seen in South East Asia (SEA) and Myanmar, but not comprehensively assessed in Bangladesh. This is due to lack of measuring parasite clearance times in response to drug treatment, a gold standard used to track artemisinin resistance (AR), in the Chittagong Hill Tracts (CHT), where >90% of malaria occurs in Bangladesh. Here we report delay in clinical parasite clearance half-lives > 5 h characteristic of AR, in Bandarban, a south-eastern rural, CHT district with escalating malaria and bordering Myanmar. Thirty-one and 68 malaria patients respectively presented in the clinic in 2018 and 2019, and this increase well correlated to the district-level malaria surge and rise in rainfall, humidity and temperature. A total of 27 patients with uncomplicated Plasmodium falciparum malaria mono-infection, after administration of an artemisinin combination therapy (ACT) showed median (range) parasite clearance half-life and time of 5.6 (1.5 – 9.6) and 24 (12–48) hours (h) respectively. The frequency distribution of parasite clearance half-life and time was bimodal, with a slower parasite clearance of 8 h in 20% of the participants. There was however, no detectable parasitemia 72 h after initiating ACT. Half-life clearance of > 5h, respectively seen in 35% and 40% of participants in 2018 and 2019, lacked in correlation to initial parasitemia, blood count parameters or resistance mutations of PfKelch13 (K13, the major parasite marker of AR). Culture adapted strains await assessment of in vitro resistance and new parasite determinants of AR.
Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses
Authors: López-Hernández Tania , Takenaka Koh-ichiro , Mori Yasunori , Kongpracha Pornparn , Nagamori Shushi , Haucke Volker , Takamori Shigeo 
Published: June 2021

ABSTRACTNeurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Conflicting models have been proposed regarding the mechanisms of SV endocytosis, most notably clathrin/ AP-2-mediated endocytosis and clathrin-independent ultrafast endocytosis. Partitioning between these pathways has been suggested to be controlled by temperature and stimulus paradigm. We report on the comprehensive survey of six major SV proteins to show that SV endocytosis in hippocampal neurons at physiological temperature occurs independent of clathrin while the endocytic retrieval of a subset of SV proteins including the vesicular transporters for glutamate and GABA depend on sorting by the clathrin adaptor AP-2. Our findings highlight a clathrin-independent role of the clathrin adaptor AP-2 in the endocytic retrieval of select SV cargos from the presynaptic cell surface and suggest a unified model for the endocytosis of SV membranes at mammalian central synapses.
Phylogenetic network analysis revealed the recombinant origin of the SARS-CoV-2 VOC202012/01 (B.1.1.7) variant first discovered in U.K.
Authors: Xie Xianfa , Lewis Teash-Juan , Green Nikoli , Wang Zhenping 
Published: June 2021

AbstractThe emergence of new variants of the SARS-CoV-2 virus poses serious problems to the control of the current COVID-19 pandemic. Understanding how the variants originate is critical for effective control of the spread of the virus and the global pandemic. The study of the virus evolution so far has been dominated by phylogenetic tree analysis, which however is inappropriate for a few important reasons. Here we used phylogenetic network approach to study the origin of the VOC202012/01 (Alpha) or so-called UK variant (PANGO Lineage B.1.1.7). The multiple network analyses using different methods consistently revealed that the VOC202012/01 variant was a result of recombination, in contrast to the common assumption that the variant evolved from step-wise mutations in a linear order. The study provides an example for the power and application of phylogenetic network analysis in studying virus evolution, which can be applied to study the evolutionary processes leading to the emergence of other variants of the SARS-CoV-2 virus as well as many other viruses.SignificanceThe emergence of new variants of the SARS-CoV-2 virus, including the Alpha variant first found in U.K., poses serious challenges to the control of the current COVID-19 pandemic. Understanding how new variant originated is paramount to end the pandemic as effectively and quickly as possible. The dominant phylogenetic tree approach to study virus evolution has been inadequate and even misleading. Here we used a phylogenetic network approach to study the origin of the VOC202012/01 (Alpha) variant which was first reported in U.K. last year but has soon spread into many other countries, leading to dramatic increase in infection and death. Multiple analyses consistently revealed that the variant originated through recombination of pre-existing virus strains, highlighting an important but largely ignored mechanism in the evolution of the SARS-CoV-2 virus so far.
Experience-dependent weakening of callosal synaptic connections in the absence of postsynaptic FMRP
Authors: Zhang Zhe , Gibson Jay R. , Huber Kimberly M. 
Published: June 2021

AbstractReduced structural and functional interhemispheric connectivity correlates with the severity of Autism Spectrum Disorder (ASD) behaviors in humans. Little is known of how ASD-risk genes regulate callosal connectivity. Here we show that Fmr1, whose loss-of-function leads to Fragile X Syndrome (FXS), cell autonomously promotes maturation of callosal excitatory synapses between somatosensory barrel cortices in mice. Postnatal, cell-autonomous deletion of Fmr1 in postsynaptic Layer (L) 2/3 or L5 neurons results in a selective weakening of AMPA receptor- (R), but not NMDA receptor-, mediated callosal synaptic function, indicative of immature synapses. Sensory deprivation by contralateral whisker trimming normalizes callosal input strength, suggesting that experience-driven activity of postsynaptic Fmr1 KO L2/3 neurons weakens callosal synapses. In contrast to callosal inputs, synapses originating from local L4 and L2/3 circuits are normal, revealing an input-specific role for postsynaptic Fmr1 in regulation of synaptic connectivity within local and callosal neocortical circuits. These results suggest direct cell autonomous and postnatal roles for FMRP in development of specific cortical circuits and suggest a synaptic basis for long-range functional underconnectivity observed in FXS patients.
Bacterial swarm-mediated phage transportation disrupts a biofilm inherently protected from phage penetration
Authors: Ratheesh Nichith K. , Calderon Cole A. , Zdimal Amanda M. , Shrivastava Abhishek 
Published: June 2021

AbstractThe treatment of chronic bacterial infections by phages has shown promise in combating antimicrobial resistance. A typical phage particle is at least an order of magnitude larger than an antibiotic molecule. Hence, phages diffuse slower than antibiotics, and can also get trapped in the polymeric mesh of biofilm matrix. By tracking fluorescently labeled lambda phages that do not infect Capnocytophaga gingivalis, a bacterium abundant in the human oral microbiota, we demonstrate active phage transportation by a C. gingivalis swarm. As a result, the rate of disruption of the prey of lambda phage i.e., an Escherichia coli colony, increases 10 times. C. gingivalis drills tunnels within a curli fiber containing E. coli biofilm and increase the efficiency of phage penetration. This provides evidence for a novel mechanism of phage-bacterial warfare.
Use of hiPSC-derived cardiomyocytes to rule out proarrhythmic effects of drugs: the case of hydroxychloroquine in COVID-19
Authors: Sala Luca , Leonov Vladislav , Mura Manuela , Moretti Alessandra , Crotti Lia , Gnecchi Massimiliano , Schwartz Peter J 
Published: June 2021

AbstractIn the early phases of the COVID-19 pandemic, drug repurposing was widely used to identify compounds that could improve the prognosis of symptomatic patients infected by SARS-CoV-2. Hydroxychloroquine (HCQ) was one of the first drugs used to treat COVID-19 patients due to its supposed capacity of inhibiting SARS-CoV-2 infection and replication in vitro.While its efficacy is debated, HCQ has been associated with QT interval prolongation and potentially Torsades de Pointes, especially in patients predisposed to developing drug-induced Long QT Syndrome (LQTS) as silent carriers of variants associated with congenital LQTS. If confirmed, these effects represent a limitation to the at-home use of HCQ for COVID-19 infection as adequate ECG monitoring may be challenging.We investigated the proarrhythmic profile of HCQ with Multi-Electrode Arrays after subchronic exposure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from two healthy donors, one asymptomatic and two symptomatic LQTS patients.We demonstrate that: I) HCQ induced a concentration-dependent Field Potential Duration (FPD) prolongation in vitro and triggered arrhythmias that halted the beating at high concentration. II) hiPSC-CMs from healthy or asymptomatic carriers tolerated higher concentrations of HCQ and showed lower susceptibility to HCQ-induced electrical abnormalities regardless of baseline FPD values. These findings agree with the clinical safety records of HCQ and demonstrated that hiPSC-CMs potentially discriminates symptomatic vs asymptomatic mutation carriers through pharmacological interventions. Disease-specific cohorts of hiPSC-CMs may be a valid preliminary addition to quickly assess drug safety in vulnerable populations, offering rapid preclinical results with valuable translational relevance for precision medicine.
RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage
Authors: Krais John J. , Wang Yifan , Patel Pooja , Basu Jayati , Bernhardy Andrea J. , Johnson Neil 
Published: June 2021

AbstractDNA damage prompts a diverse range of alterations to the chromatin landscape. The RNF168 E3 ubiquitin ligase catalyzes the mono-ubiquitination of histone H2A at lysine (K)13/15 (mUb-H2A), forming a binding module for DNA repair proteins. BRCA1 promotes homologous recombination (HR), in part, through its interaction with PALB2, and the formation of a larger BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex. The mechanism by which BRCA1-P is recruited to chromatin surrounding DNA breaks is unclear. In this study, we reveal that an RNF168-governed signaling pathway is responsible for localizing the BRCA1-P complex to DNA damage. Using mice harboring a Brca1CC (coiled coil) mutation that blocks the Brca1-Palb2 interaction, we uncovered an epistatic relationship between Rnf168- and Brca1CC alleles, which disrupted development, and reduced the efficiency of Palb2-Rad51 localization. Mechanistically, we show that RNF168-generated mUb-H2A recruits BARD1 through a BRCT domain ubiquitin-dependent recruitment motif (BUDR). Subsequently, BARD1-BRCA1 accumulate PALB2-RAD51 at DNA breaks via the CC domain-mediated BRCA1-PALB2 interaction. Together, these findings establish a series of molecular interactions that connect the DNA damage signaling and HR repair machinery.
Comparing Imaging Biomarkers of Cerebral Edema after TBI in Young Adult Male and Female Rats
Authors: Minchew Heather M , Ferren Sadie L , Christian Sarah K , Hu Jinxiang , Keselman Paul , Brooks William M , Andrews Brian T , Harris Janna L 
Published: June 2021

ABSTRACTTraumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 hours after unilateral contusive TBI in male and female rats. We then directly quantified brain water content in the same subjects ex vivo. We found that both males and females had similarly elevated T2 values after TBI compared with sham controls. Apparent diffusion coefficient (ADC) was more variable than T2 and did not show significant injury effects in males or females. Brain water was elevated in male TBI rats compared with sham controls, but there was no difference between female TBI and sham groups. Notably, MRI biomarkers of edema were more closely correlated with brain water in male rats; female rats did not show any relationship between brain water and T2 or ADC. These observations raise questions about the interpretation of radiological findings traditionally interpreted as edema in female TBI patients. A better understanding of sex differences and similarities in the pathophysiology of post-traumatic edema is needed to help improve patient management and the development of effective treatment strategies for men and women.
Functional diversification gave rise to allelic specialization in a rice NLR immune receptor pair
Authors: De la Concepcion Juan Carlos , Benjumea Javier Vega , Białas Aleksandra , Terauchi Ryohei , Kamoun Sophien , Banfield Mark J. 
Published: June 2021

SummaryCooperation between receptors from the NLR superfamily is important for intracellular activation of immune responses. NLRs can function in pairs that, upon pathogen recognition, trigger hypersensitive cell death and stop pathogen invasion. Natural selection drives specialization of host immune receptors towards an optimal response, whilst keeping a tight regulation of immunity in the absence of pathogens. However, the molecular basis of co-adaptation and specialization between paired NLRs remains largely unknown. Here, we describe functional specialization in alleles of the rice NLR pair Pik that confers resistance to strains of the blast fungusMagnaporthe oryzaeharbouring AVR-Pik effectors. We revealed that matching pairs of allelic Pik NLRs mount effective immune responses whereas mismatched pairs lead to autoimmune phenotypes, a hallmark of hybrid necrosis in both natural and domesticated plant populations. We further showed that allelic specialization is largely underpinned by a single amino acid polymorphism that determines preferential association between matching pairs of Pik NLRs. These results provide a framework for how functionally linked immune receptors undergo co-adaptation to provide an effective and regulated immune response against pathogens. Understanding the molecular constraints that shape paired NLR evolution has implications beyond plant immunity given that hybrid necrosis can drive reproductive isolation.