bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of early community transmission of Omicron (B1.1.529) in Delhi- A city with very high seropositivity and past-exposure!
Authors: Garg Rahul , Gautam Pramod , Suroliya Varun , Agarwal Reshu , Bhugra Arjun , Kaur Urvinder S. , Das Santanu , Bihari Chhagan , Agarwal Anil , Sarin S. K , Gupta Ekta 
Published: January 2022

SummaryBackgroundSince identification, infections by new SARS-CoV-2 variant Omicron are rapidly increasing worldwide. There is huge gap of knowledge regarding virus behaviour in the population from low and middle income countries. Delhi being unique population with a high seropositivity and vaccination rate against COVID-19 infection. We aimed to study the epidemiological and clinical presentations of few early cases of community spread of Omicron infection in the state.MethodsThis is a prospective study where respiratory specimen from all RT-PCR confirmed positive cases between November 25th-December 23rd 2021 collected from five districts of Delhi were subjected to whole genome sequencing. Complete demographic and clinical details were recorded. We also analyzed the formation of local and familial clusters and eventual community transmission.FindingsOut of the 264 cases included during study period, 68.9% (n=182)were identified as Delta and its sub-lineages while 31.06% (n=82) were Omicron with BA.1 as the predominant sub-lineage (73.1%). Most of the Omicron cases were asymptomatic (n=50,61%) and not requiring any hospitalizations. A total of 72 (87.8%) cases were fully vaccinated. 39.1% (n=32) had a history of travel and/or contacts while 60.9 (n=50) showed a community transmission. A steep increase in the daily progression of Omicron cases with its preponderance in the community was observed from 1.8% to 54%.InterpretationThis study is among the first from India to provide the evidence of community transmission of Omicron with significantly increased breakthrough infections, decreased hospitalization rates, and lower rate of symptomatic infections among individuals with high seropositivity against SARS-CoV-2 infections.
Hippocampal Transplants of Fetal GABAergic Progenitors Regulate Adult Neurogenesis in Mice with Temporal Lobe Epilepsy
Authors: Arshad Muhammad N. , Oppenheimer Simon , Jeong Jaye , Buyukdemirtas Bilge , Naegele Janice R. 
Published: January 2022

ABSTRACTGABAergic interneurons within the dentate gyrus of the hippocampus regulate adult neurogenesis, including proliferation, migration, and maturation of new granule cells born in the subgranular zone (SGZ) of the dentate gyrus (DG). In temporal lobe epilepsy (TLE), some adult-born granule cells migrate ectopically into the hilus, and these cells contribute to increased hyperexcitability and seizures. Yet, transplanting embryonic day 13.5 fetal mouse medial ganglionic eminence (MGE) GABAergic progenitors into the hippocampus of mice with TLE ameliorates spontaneous seizures, due in part, to increased postsynaptic inhibition of adult-born granule cells. Here, we asked whether MGE progenitor transplantation affects earlier stages of adult neurogenesis, by comparing patterns of neurogenesis in naïve mice and epileptic (TLE) mice, with or without MGE transplants. In naïve and TLE mice, transplanted MGE cells showed comparable migration and process outgrowth. However, in TLE mice with MGE transplants, fewer adult-born Type 3 progenitors migrated ectopically. Furthermore, more Type 3 progenitors survived and migrated into the granule cell layer (GCL), as determined by immunostaining for doublecortin or the thymidine analogue, bromodeoxyuridine (BrdU). To determine whether MGE transplants affected earlier stages of adult neurogenesis, we compared proliferation in the SGZ two-hours after pulse labeling with BrdU in Naive vs. TLE mice and found no significant differences. Furthermore, MGE progenitor transplantation had no effect on cell proliferation in the SGZ. Moreover, when compared to naïve mice, TLE mice showed increases in inverted Type 1 progenitors and Type 2 progenitors, concomitant with a decrease in the normally oriented radial Type 1 progenitors. Strikingly, these alterations were abrogated by MGE transplantation. Thus, MGE transplants appear to reverse seizure-induced abnormalities in adult neurogenesis by increasing differentiation and radial migration of adult-born granule cell progenitors, outcomes that may ameliorate seizures.
PFTK1 kinase regulates axogenesis during development via RhoA activation
Authors: Rodríguez González Yasmilde , Kamkar Fatemeh , Jafar-nejad Paymaan , Wang Suzi , Qu Dianbo , Sanchez Alvarez Leticia , Hawari Dina , Sonnenfeld Margaret , Slack Ruth S. , Albert Paul , Park David S. , Joselin Alvin 
Published: January 2022

AbstractPFTK1/Eip63E is a member of the Cyclin-dependent kinases (CDKs) family and plays an important role in normal cell cycle progression. Eip63E expresses primarily in postnatal and adult nervous system in Drosophila melanogaster but its role in CNS development remains unknown. We sought to understand the function of Eip63E in the CNS by studying the fly ventral nerve cord during development. Our results demonstrate that Eip63E regulates axogenesis in neurons and its deficiency leads to neuronal defects. Functional interaction studies performed using the same system identify an interaction between Eip63E and the small GTPase Rho1. Furthermore, deficiency of Eip63E homolog in mice, PFTK1, in a newly generated PFTK1 knockout mice results in increased axonal outgrowth confirming that the developmental defects observed in the fly model are due to defects in axogenesis. Importantly, RhoA phosphorylation and activity is affected by PFTK1 in primary neuronal cultures. We here report that GDP bound inactive RhoA is a substrate of PFTK1 and PFTK1 phosphorylation is required for RhoA activity. In conclusion, our work establishes an unreported neuronal role of PFTK1 in axon development mediated by phosphorylation and activation of GDP-bound RhoA. The results presented add to our understanding of the role of Cdks in the maintenance of RhoA mediated axon growth and its impact on CNS development and axonal regeneration.
Global monitoring of soil animal communities using a common methodology
Authors: Potapov Anton M. , Sun Xin , Briones Maria J. I. , Brown George G. , Cameron Erin K. , Cortet Jérôme , Eisenhauer Nico , Fujii Saori , Geisen Stefan , Gongalsky Konstantin B. , Guerra Carlos , Handa I.Tanya , Janion-Scheepers Charlene , Lindo Zoë , Mathieu Jérôme , Murvanidze Maka , Nielsen Uffe N , Scheu Stefan , Schmidt Olaf , Schneider Clement , Seeber Julia , Tuma Jiri , Tiunov Alexei V. , Zaitsev Andrey S. , Wall Diana H. 
Published: January 2022

SummaryHere we introduce the Soil BON Foodweb Team, a cross-continental collaborative network that aims to monitor soil animal communities and food webs using consistent methodology at a global scale. Soil animals support vital soil processes via soil structure modification, direct consumption of dead organic matter, and interactions with microbial and plant communities. Soil animal effects on ecosystem functions have been demonstrated by correlative analyses as well as in laboratory and field experiments, but these studies typically focus on selected animal groups or species at one or few sites with limited variation in environmental conditions. The lack of comprehensive harmonised large-scale soil animal community data including microfauna, mesofauna, and macrofauna, in conjunction with related soil functions, limits our understanding of biological interactions in soil communities and how these interactions affect ecosystem functioning. To provide such data, the Soil BON Foodweb Team invites researchers worldwide to use a common methodology to address six long-term goals: (1) to collect globally representative harmonised data on soil micro-, meso-, and macrofauna communities; (2) to describe key environmental drivers of soil animal communities and food webs; (3) to assess the efficiency of conservation approaches for the protection of soil animal communities; (4) to describe soil food webs and their association with soil functioning globally; (5) to establish a global research network for soil biodiversity monitoring and collaborative projects in related topics; (6) to reinforce local collaboration networks and expertise and support capacity building for soil animal research around the world. In this paper, we describe the vision of the global research network and the common sampling protocol to assess soil animal communities and advocate for the use of standard methodologies across observational and experimental soil animal studies. We will use this protocol to conduct soil animal assessments and reconstruct soil food webs on the sites included in the global soil biodiversity monitoring network, Soil BON, allowing us to assess linkages among soil biodiversity, vegetation, soil physico-chemical properties, and ecosystem functions. In the present paper, we call for researchers especially from countries and ecoregions that remain underrepresented in the majority of soil biodiversity assessments to join us. Together we will be able to provide science-based evidence to support soil biodiversity conservation and functioning of terrestrial ecosystems.
Loss of plastid developmental genes coincides with a reversion to monoplastidy in hornworts
Authors: MacLeod Alexander I. , Raval Parth K. , Stockhorst Simon , Knopp Michael R. , Frangedakis Eftychios , Gould Sven B. 
Published: January 2022

ABSTRACTThe first plastid evolved from an endosymbiotic cyanobacterium in the common ancestor of the Archaeplastida. The transformative steps from cyanobacterium to organelle included the transfer of control over developmental processes; a necessity for the host to orchestrate, for example, the fission of the organelle. The plastids of almost all embryophytes divide independent from nuclear division, leading to cells housing multiple plastids. Hornworts, however, are monoplastidic (or near-monoplastidic) and their photosynthetic organelles are a curious exception among embryophytes for reasons such as the occasional presence of pyrenoids. Here we screened genomic and transcriptomic data of eleven hornworts for components of plastid developmental pathways. We find intriguing differences among hornworts and specifically highlight that pathway components involved in regulating plastid development and biogenesis were differentially lost in this group of bryophytes. In combination with ancestral state reconstruction, our data suggest that hornworts have reverted back to a monoplastidic phenotype due to the combined loss of two plastid division-associated genes: ARC3 and FtsZ2.
Generation and characterisation of P. falciparum parasites with a G358S mutation in the PfATP4 Na+ pump and clinically relevant levels of resistance to some PfATP4 inhibitors
Authors: Qiu Deyun , Pei Jinxin V. , Rosling James E. O. , Li Dongdi , Xue Yi , Penington Jocelyn Sietsma , Kümpornsin Krittikorn , Vincent Aw Yi Tong , Han Aw Jessica Yi , Hasemer Heath , Dennis Adelaide S. M. , Ridgway Melanie C. , Papenfuss Anthony T. , Lee Marcus C. S. , van Dooren Giel G. , Kirk Kiaran , Lehane Adele M. 
Published: January 2022

AbstractSmall-molecule inhibitors of PfATP4, a Plasmodium falciparum protein that is believed to pump Na+ out of the parasite while importing H+, are on track to become much-needed new antimalarial drugs. The spiroindolone cipargamin is poised to become the first PfATP4 inhibitor to reach the field, having performed strongly in Phase 1 and 2 clinical trials. Previous attempts to generate cipargamin-resistant parasites in the laboratory have yielded parasites with reduced susceptibility to the drug; however, the highest 50% inhibitory concentration reported to date is 24 nM. Here, we show that P. falciparum parasites can acquire a clinically-significant level of resistance to cipargamin that enables them to withstand micromolar concentrations of the drug. Independent experiments to generate high-level cipargamin resistance using different protocols and strains led to the same change each time – a G358S mutation in PfATP4. Parasites with this mutation showed high-level resistance not only to cipargamin, but also to the dihydroisoquinolone (+)-SJ733. However, for certain other (less clinically advanced) PfATP4-associated compounds the G358S mutation in PfATP4 conferred only moderate resistance or no resistance. The G358S mutation in PfATP4 did not affect parasite susceptibility to antimalarials that do not target PfATP4. The G358S mutation in PfATP4, and the equivalent mutation in the Toxoplasma gondii ATP4 homologue (G419S), decreased the sensitivity of the Na+-ATPase activity of ATP4 to inhibition by cipargamin and (+)-SJ733, and decreased the sensitivity of parasites expressing these ATP4 mutations to disruption of parasite Na+ regulation by cipargamin- and (+)-SJ733. The G358S mutation in PfATP4 reduced the affinity of the protein for Na+ and was associated with an increase in the parasite’s resting cytosolic Na+ concentration; however, no significant defect in parasite growth rate was observed. Our findings suggest that codon 358 in pfatp4 should be monitored closely in the field as a molecular marker for cipargamin resistance, and that PfATP4 inhibitors in clinical development should be tested for their activity against PfATP4G358S parasites.
Optimal control methods for nonlinear parameter estimation in biophysical neuron models
Authors: Kadakia Nirag 
Published: January 2022

AbstractFunctional forms of biophysically-realistic neuron models are constrained by neurobiological and anatomical considerations, such as cell morphologies and the presence of known ion channels. Despite these constraints, neurons models still contain unknown static parameters which must be inferred from experiment. This inference task is most readily cast into the framework of state-space models, which systematically takes into account partial observability and measurement noise. Inferring only dynamical state variables such as membrane voltages is a well-studied problem, and has been approached with a wide range of techniques beginning with the well-known Kalman filter. Inferring both states and fixed parameters, on the other hand, is less straightforward. Here, we develop a method for joint parameter and state inference that combines traditional state space modeling with chaotic synchronization and optimal control. Our methods are tailored particularly to situations with considerable measurement noise, sparse observability, very nonlinear or chaotic dynamics, and highly uninformed priors. We illustrate our approach both in a canonical chaotic model and in a phenomenological neuron model, showing that many unknown parameters can be uncovered reliably and accurately from short and noisy observed time traces. Our method holds promise for estimation in larger-scale systems, given ongoing improvements in calcium reporters and genetically-encoded voltage indicators.
Horizontal Transfers Lead to the Birth of Momilactone Biosynthetic Gene Clusters in Grass
Authors: Wu Dongya , Hu Yiyu , Akashi Shota , Nojiri Hideaki , Ye Chu-Yu , Zhu Qian-Hao , Okada Kazunori , Fan Longjiang 
Published: January 2022

AbstractMomilactone A, an important plant labdane-related diterpenoid, functions as a phytoalexin against pathogens and an allelochemical against neighboring plants. The genes involved in biosynthesis of momilactone A are found in clusters, i.e., MABGCs (Momilactone A biosynthetic gene clusters), in the rice and barnyardgrass genomes. How MABGCs originate and evolve is still not clear. Here, we integrated results from comprehensive phylogeny and comparative genomic analyses of the core genes of MABGC-like clusters and MABGCs in 40 monocot plant genomes, providing convincing evidence for the birth and evolution of MABGCs in grass species. The MABGCs found in the PACMAD clade of the core grass lineage (including Panicoideae and Chloridoideae) originated from a MABGC-like cluster in Triticeae (BOP clade) via horizontal gene transfer (HGT) and followed by recruitment of MAS and CYP76L1 genes. The MABGCs in Oryzoideae originated from PACMAD through another HGT event and lost CYP76L1 afterwards. The Oryza MABGC and another Oryza diterpenoid cluster c2BGC are two distinct clusters, with the latter being originated from gene duplication and relocation within Oryzoideae. Further comparison of the expression patterns of the MABGC genes between rice and barnyardgrass in response to pathogen infection and allelopathy provides novel insights into the functional innovation of MABGCs in plants. Our results demonstrate HGT-mediated origination of MABGCs in grass and shed lights into the evolutionary innovation and optimization of plant biosynthetic pathways.
A unique dexamethasone-dependent gene expression profile in the lungs of COVID-19 patients
Authors: Fahnøe Ulrik , Ronit Andreas , Berg Ronan M. G. , Jørgensen Sofie E. , Mogensen Trine H. , Underwood Alexander P. , Scheel Troels K. H. , Bukh Jens , Plovsing Ronni R. 
Published: January 2022

AbstractLocal immunopathogenesis of COVID-19 acute respiratory distress syndrome (CARDS) and the effects of systemic dexamethasone (DXM) treatment on pulmonary immunity in COVID-19 remain insufficiently understood. To provide further insight into insight into immune regulatory mechanisms in the lungs of CARDS (with and without DXM treatment) and critically ill non-COVID-19 patients (without DXM treatment), transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid (BALF) was performed in these patients. Functional analysis was performed using gene ontology and a blood transcription module, and gene expression of select pro-inflammatory cytokines, interferon-stimulated genes (ISGs) and auto-IFN antibodies were assessed. We found 550 and 2173 differentially expressed genes in patients with non-DXM-CARDS and DXM-CARDS, respectively. DXM-CARDS was characterized by upregulation of genes related to pulmonary innate and adaptive immunity, notably B-cell and complement pathway activation, antigen presentation, phagocytosis and FC-gamma receptor signalling. Pro-inflammatory genes were not differentially expressed in CARDS vs. non-COVID-19, nor did they differ according to DXM. Most ISGs were specifically upregulated in CARDS, particularly in non-DXM-CARDS. Auto-IFN autoantibodies were detectable in BALF of some CARDS patients. In conclusion, DXM treatment was not associated with regulation of pro-inflammatory pathways in CARDS but with regulation of other specific local innate and adaptive immune responses.summaryThis study identifies differentially expressed genes in bronchoalveolar fluid of COVID-19 acute respiratory distress patients with a distinct RNA expression profile of those treated with dexamethasone. These results challenge the concept of a COVID-19 specific cytokine storm.
Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunisation Stress-related Responses with COVID-19 mRNA Vaccine
Authors: Imai Kazuo , Tanaka Fumika , Kawano Shuichi , Esaki Kotoba , Arakawa Junko , Nishiyama Takashi , Seno Soichiro , Hatanaka Kosuke , Sugiura Takao , Kodama Yu , Yamada Seigo , Iwamoto Shinichiro , Takesima Shigeto , Abe Nobujiro , Kamae Chikako , Aono Shigeaki , Ito Toshimitsu , Yamamoto Tetsuo , Mizuguchi Yasunori 
Published: January 2022

AbstractBackgroundWith the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated.ObjectiveWe aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunisation stress-related responses (ISRR) with the Moderna COVID-19 vaccine.MethodsThis nested case-control study included recipients who received the Moderna vaccine at a mass vaccination centre, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1:4) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR.ResultsOf the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2,478 recipients (cases 2) showed 318 events of IHSR and 2,558 events of ISRR, respectively. The incidence rates per million doses were estimated as – IHSR: 266 cases, ISRR: 2,129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and history of allergy; for ISRR, they were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex.ConclusionIn the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should beware of the occurrence of ISRR. Risk factor identification may contribute to the stratification of high-risk recipients for IHSR and ISRR.
Evidence from human placenta, ER-stressed trophoblasts and transgenic mice links transthyretin proteinopathy to preeclampsia
Authors: Cheng Shibin , Huang Zheping , Banerjee Sayani , Buxbaum Joel N. , Sharma Surendra 
Published: January 2022

ABSTRACTWe have demonstrated that protein aggregation plays a pivotal role in the pathophysiology of preeclampsia (PE) and identified several aggregated proteins in the circulation of PE patients, most significantly the serum protein transthyretin (TTR). Here we show robust accumulation of TTR aggregates in the placentas of women with early-onset PE (e-PE). TTR aggregation was inducible in primary human trophoblasts (PHTs) and the TCL-1 trophoblast cell line by ER stress inducers or autophagy-lysosomal disruptors. Hypoxia/reoxygenation (H/R) of cultured PHTs increased intracellular BiP, phosphorylated IRE1α, PDI and Ero-1, all markers of the UPR, and the apoptosis mediator caspase-3. Blockade of IRE1α inhibited H/R-induced upregulation of Ero-1 in PHTs. Excessive UPR was observed in the PE placenta. Further, pregnant mice, overexpressing transgene encoded wild type human TTR, displayed aggregated TTR in the junctional zone of the placenta and PE-like features including hypertension, proteinuria, intrauterine growth restriction, kidney injury, and elevated levels of the PE biomarkers serum sFlt-1 and endoglin. High Resolution Ultrasound analysis revealed low blood flow in uterine and umbilical arteries compared to that found in wild type pregnant mice. On the other hand, loss of mouse TTR function did not cause any pregnancy abnormalities in Ttr-/- mice. These observations in the PE placenta, cultured trophoblast cells and TTR transgenic mice indicate that TTR aggregation is an important causal contributor to PE pathophysiology.