bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies of vegetation and land-use history on Bodmin Moor: pollen investigations from Leskernick
Authors: Waller Martyn 
Published: January 2024

AbstractDetails of pollen investigations that accompanied archaeological excavations (of a Late Neolithic/Early Bronze ritual complex and a Middle to Late Bronze Age settlement) at Leskernick Hill Bodmin Moor, undertaken between 1995 and 1999, are presented. Samples were collected both from a nearby ‘off-site’ location and from a variety of ‘on-site’ contexts. The off-site peat profile contains a major hiatus. The earliest assemblage corresponds to the Late Neolithic/Early Bronze Age and indicates a largely open landscape in which both pasture and arable agriculture were practiced. Sedimentation recommenced during the early Medieval period and the pollen record shows the varying degrees to which grazing and arable agriculture were practiced up until the recent past. These phases do not accord well with historic evidence from the wider area, though other pollen diagrams from the region also record a wetter phase found at Leskernick (and dated here toc. 1400-1600 AD). Evidence obtained during the archaeological excavations suggests the ritual complex was abandoned early and the pollen records indicate this was accompanied by a period of low grazing pressure. Samples from the interiors of huts/houses dated to the Middle Bronze Age are dominated by Poaceae pollen suggesting relatively intense human activity. The assemblages from beneath the boundary walls around the settlement probably cover a considerable time period, in part as a result of rebuilding and the reuse of stone. With highCalluna vulgarisvalues they appear largely to reflect the stony nature of the environment in which the settlement was established.PreambleThis pre-print details the results of pollen investigations that accompanied archaeological excavations at Leskernick Hill, Bodmin Moor, undertaken between 1995 and 1999. A draft manuscript was prepared for publication in 2005, but the monograph in which it was to be included outlining the excavations, has not been forthcoming. Details of the archaeological/historic features present at Leskernick can be found in Johnson and Rose (1994) and Herringet al. (2008), while Benderet al. (2007) provides information on the work that these investigations formed part of. The 2005 manuscript is reproduced here with a new introduction and revisions incorporating information from the later publications.
Development of an optogenetic gene expression system inLactococcus lactisusing a split photoactivatable T7 RNA polymerase
Authors: Rodrigo-Navarro Aleixandre , Salmeron-Sanchez Manuel 
Published: January 2024

AbstractCellular processes can be modulated by physical means, such as light, which offers advantages over chemically inducible systems with respect to spatiotemporal control. Here we introduce an optogenetic gene expression system forLactococcus lactisthat utilizes a split T7 RNA polymerase linked to two variants of the Vivid regulators. Depending on the chosen photoreceptor variant, either ‘Magnets’ or ‘enhanced Magnets’, this system can achieve either high protein expression levels or low basal activity in the absence of light, exhibiting a fold induction close to 30, rapid expression kinetics, and heightened light sensitivity. This system functions effectively in liquid cultures and within cells embedded in hydrogel matrices, highlighting its potential in the development of novel engineered living materials capable of responding to physical stimuli such as light. The optogenetic component of this system is highly customizable, allowing for the adjustment of expression patterns through modifications to the promoters and/or engineered T7 RNA polymerase variants. We anticipate that this system can be broadly adapted to other Gram-positive hosts with minimal modifications required.
Spontaneous activity of striatal projection neurons supports maturation of striatal inputs to substantia nigra dopaminergic neurons
Authors: Kokinovic Bojana , Seja Patricia , Donati Angelica , Ryazantseva Maria , de Kerchove d’Exaerde Alban , Schiffmann Serge N. , Taira Tomi , Molchanova Svetlana M. 
Published: January 2024

AbstractSpontaneous activity of neurons during early ontogenesis is instrumental for stabilization and refinement of developing neuronal connections. The role of spontaneous activity in synaptic development has been described in detail for cortical-like structures. Yet, very little is known about activity-dependent development of long-range inhibitory projections, such as projections from striatum. Here, we show that striatal projection neurons (SPNs) in dorsal striatum are spontaneously active in P4-P14 mice. Spontaneous activity was detected in both direct-pathway SPNs (dSPNs) and indirect-pathway SPNs (iSPNs). Most of the spontaneously active cells were in striosomes – a chemical compartment in striatum defined by expression of µ-opioid receptor. Higher excitability of both striosomal dSPNs and iSPNs was related to their intrinsic excitability properties (higher action potential half-width and IV slope). Tonic activation of muscarinic M1 receptor maintains the spontaneous activity of striosomal SPNs, the effect being stronger in iSPNs and weaker in dSPNs. To investigate if the neonatal spontaneous activity is needed for the stabilization of SPN long-range projections, we chemogenetically inhibited striosomal SPNs in neonatal animals and studied the efficiency of striatonigral projections in adult animals. Inhibition of striosomal SPNs by chronic CNO administration to P6-14 pups caused a reduction in the functional GABAergic innervation and in the density of gephyrin puncta in dopaminergic neurons of substantia nigra pars compacta of the adult (P52-79) animals. Chronic administration of CNO later in development (P21-29), on the contrary, resulted in higher mIPSC frequency in dopaminergic cells of the adult animals. Thus, the activity-dependent stabilization of striosomal projections has different developmental phases, and the long-term outcome of perturbations in these processes depends on the developmental period when they occur. Taken together, our results demonstrate that spontaneous activity of SPNs is essential for the maturation and stabilization of striatal efferents.
Interpretable deep learning for deconvolutional analysis of neural signals
Authors: Tolooshams Bahareh , Matias Sara , Wu Hao , Temereanca Simona , Uchida Naoshige , Murthy Venkatesh N. , Masset Paul , Ba Demba 
Published: January 2024

AbstractThe widespread adoption of deep learning to build models that capture the dynamics of neural populations is typically based on “black-box” approaches that lack an interpretable link between neural activity and network parameters. Here, we propose to apply algorithm unrolling, a method for interpretable deep learning, to design the architecture of sparse deconvolutional neural networks and obtain a direct interpretation of network weights in relation to stimulus-driven single-neuron activity through a generative model. We characterize our method, referred to as deconvolutional unrolled neural learning (DUNL), and show its versatility by applying it to deconvolve single-trial local signals across multiple brain areas and recording modalities. To exemplify use cases of our decomposition method, we uncover multiplexed salience and reward prediction error signals from midbrain dopamine neurons in an unbiased manner, perform simultaneous event detection and characterization in somatosensory thalamus recordings, and characterize the heterogeneity of neural responses in the piriform cortex and in the striatum during unstructured, naturalistic experiments. Our work leverages the advances in interpretable deep learning to gain a mechanistic understanding of neural activity.
Connexin43 in mesenchymal lineage cells regulates body adiposity and energy metabolism in mice
Authors: Lee Seung-Yon , Fontana Francesca , Sugatani Toshifumi , Castillo Ignacio Portales , Leanza Giulia , Coler-Reilly Ariella , Civitelli Roberto 
Published: January 2024

AbstractConnexin43 (Cx43) is the most abundant gap junction protein present in the mesenchymal lineage. In mature adipocytes, Cx43 mediates white adipose tissue (WAT) “beiging” in response to cold exposure and maintains the mitochondrial integrity of brown adipose tissue (BAT). We found that genetic deletion ofGja1(Cx43 gene) in cells that give rise to chondro-osteogenic and adipogenic precursors driven by theDermo1/Twist2promoter leads to lower body adiposity and partial protection against the weight gain and metabolic syndrome induced by a high fat diet (HFD) in both sexes. These protective effects from obesogenic diet are related to increased locomotion, fuel utilization, energy expenditure, non-shivering thermogenesis, and better glucose tolerance in conditionallyGja1ablated mice. Accordingly,Gja1mutant mice exhibit reduced adipocyte hypertrophy, partially preserved insulin sensitivity, increased BAT lipolysis and decreased whitening under HFD. This metabolic phenotype is not reproduced with more restrictedGja1ablation in differentiated adipocytes, suggesting that Cx43 has a hitherto unknown function in adipocyte progenitors or other targeted cells, resulting in restrained energy expenditures and fat accumulation. These results disclose an hitherto unknown action of Cx43 in adiposity, and offer a promising new pharmacologic target for improving metabolic balance in diabetes and obesity.Graphical Abstract
Rapid Emergence and Evolution of SARS-CoV-2 Variants in Advanced HIV Infection
Authors: Ko Sung Hee , Radecki Pierce , Belinky Frida , Bhiman Jinal N. , Meiring Susan , Kleynhans Jackie , Amoako Daniel , Guerra Canedo Vanessa , Lucas Margaret , Kekana Dikeledi , Martinson Neil , Lebina Limakatso , Everatt Josie , Tempia Stefano , Bylund Tatsiana , Rawi Reda , Kwong Peter D. , Wolter Nicole , von Gottberg Anne , Cohen Cheryl , Boritz Eli A. 
Published: January 2024

AbstractPrevious studies have linked the evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic variants to persistent infections in people with immunocompromising conditions1–4, but the evolutionary processes underlying these observations are incompletely understood. Here we used high-throughput, single-genome amplification and sequencing (HT-SGS) to obtain up to ∼103SARS-CoV-2 spike gene sequences in each of 184 respiratory samples from 22 people with HIV (PWH) and 25 people without HIV (PWOH). Twelve of 22 PWH had advanced HIV infection, defined by peripheral blood CD4 T cell counts (i.e., CD4 counts) <200 cells/μL. In PWOH and PWH with CD4 counts ≥200 cells/μL, most single-genome spike sequences in each person matched one haplotype that predominated throughout the infection. By contrast, people with advanced HIV showed elevated intra-host spike diversity with a median of 46 haplotypes per person (IQR 14-114). Higher intra-host spike diversity immediately after COVID-19 symptom onset predicted longer SARS-CoV-2 RNA shedding among PWH, and intra-host spike diversity at this timepoint was significantly higher in people with advanced HIV than in PWOH. Composition of spike sequence populations in people with advanced HIV fluctuated rapidly over time, with founder sequences often replaced by groups of new haplotypes. These population-level changes were associated with a high total burden of intra-host mutations and positive selection at functionally important residues. In several cases, delayed emergence of detectable serum binding to spike was associated with positive selection for presumptive antibody-escape mutations. Taken together, our findings show remarkable intra-host genetic diversity of SARS-CoV-2 in advanced HIV infection and suggest that adaptive intra-host SARS-CoV-2 evolution in this setting may contribute to the emergence of new variants of concern (VOCs).
Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease
Authors: Shakiba Saeed , Haddadi Nazgol-Sadat , Afshari Khashayar , Lubov Janet E. , Raef Haya S. , Li Robert , Yildiz-Altay Ümmügülsüm , Daga Mridushi , Refat Maggi Ahmed , Kim Evangeline , Galindo de Laflin Johanna , Akabane Andressa , Sherman Shany , MacDonald Elizabeth , Strassner James P. , Zhang Liang , Leon Michael , Baer Christina E. , Dresser Karen , Liang Yan , Whitley James B , Skopelja-Gardner Sladjana , Harris John E , Deng April , Vesely Matthew D. , Rashighi Mehdi , Richmond Jillian 
Published: January 2024

AbstractChemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics. Flow and Olink data concordantly demonstrated significant increases in T cells and antigen presenting cells (APCs). We also performed spatial transcriptomics and spatial proteomics of punch biopsies using digital spatial profiling (DSP) technology on CLE skin and healthy margin controls to examine discreet locations within the tissue. Spatial and Olink data confirmed elevation of interferon (IFN) and IFN-inducible CXCR3 chemokine ligands. Comparing involved versus uninvolved keratinocytes in CLE samples revealed upregulation of essential inflammatory response genes in areas near interface dermatitis, includingAIM2. Our Olink data confirmed upregulation of Caspase 8, IL-18 which is the final product of AIM2 activation, and induced chemokines including CCL8 and CXCL6 in CLE lesional samples. Chemotaxis assays using PBMCs from healthy and CLE donors revealed that T cells are equally poised to respond to CXCR3 ligands, whereas CD14+CD16+ APC populations are more sensitive to CXCL6 via CXCR1 and CD14+ are more sensitive to CCL8 via CCR2. Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6/CXCR1 and CCL8/CCR2, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3.One Sentence SummaryWe mapped chemokine orchestrators of interface dermatitis in lupus using spatial approaches on archival tissue and confirmed with fresh tissues.
Evidence forNR2F2/COUP-TFII involvement in human testis development
Authors: Wankanit Somboon , Zidoune Housna , Bignon-Topalovic Joëlle , Schlick Laurène , Houzelstein Denis , Fusée Leila , Boukri Asma , Nouri Nassim , McElreavey Ken , Bashamboo Anu , Elzaiat Maëva 
Published: January 2024

AbstractNR2F2encodes COUP-TFII, an orphan nuclear receptor involved in mammalian gonadogenesis. COUP-TFII is expressed in the interstitial/stromal compartment of both fetal testes and ovaries, where it is required for developing steroidogenic lineages. Pathogenic variants in humanNR2F2are linked to testis formation in 46,XX individuals (46,XXdisorders ofsexdevelopment, 46,XX DSD). Such findings propose a regulatory role of COUP-TFII in the developing ovary, whereas its function in testis remains unknown. We evaluate the effect of ade novoheterozygous, predicted damaging, missense variant inNR2F2(p.Arg246His) in a 46,XY under-masculinized boy.In-vitroassays show that the mutant protein significantly loses the inhibitory effect on NR5A1-mediated activation of both theLHBandINSL3promoters. The data support the pathogenicity of the p.Arg246His variant in 46,XY DSD and a role forNR2F2in human testis formation. In addition toNR5A1andWT1,NR2F2variants are thus associated with both 46,XX and 46,XY DSD. This expands the list of genes that function in both male and female sex development, which is originally thought to be regulated by two entirely different sets of genes.
Nitrogen Management on Improving Resilience of Flood-Tolerant (Sub1) Rice Varieties in Flood-Prone Rainfed Lowlands
Authors: Singh A. K. , Pandey A. K. , Singh Ankit , Tiwari Deeksha , Singh Bijendra 
Published: January 2024

AbstractFlash flood causing submergence adversely affects rice production in vast areas of rainfed lowlands of South and Southeast Asia. Introgression at the Sub1 locus by molecularly assisted backcrossing incorporated tolerance into varieties traditional/modern high-yielding varieties and has released some varieties for commercial planting by Indian farmers. In the present study, we investigated the application of fractional N to further improve the survival and productivity potential of two Sub1 introgression varieties, Sambha Mahsuri-Sub1, and BR11-Sub1.Thirty days (d) old seedlings were transplanted, and 28-d after transplanting i.e. 58 days old seedlings were completely submerged for 18-d. Full doses of phosphorus and potassium were applied as a basal, while nitrogen was applied in split doses. Plant survival was recorded at 0, 5 and 20 days after de-submergence (AS) to study the recovery dynamics of cultivar Sub1. Results evidently established that varieties with higher biomass, tiller number, total chlorophyll and soluble sugars concentrations before flooding have higher survival rates after water drainage. They also had faster growth and better recovery, which was reflected in yield characteristics and grain yield. The 20-day and 40- day AS N application replenished flood-disturbed soil N pools, resulting in higher N uptake and N-use efficiency. These results may contribute to better nitrogen fertilization programs for rice crops and improve stress tolerance in newly developed tolerant rice varieties. It is evident from perusal of results that treatment T2i.e.1/4 N applied as a basal and rest of residual N applied in three split doses respectively after de-submergence on days 5, 20 and 40 resulted in higher survival thanT1 and T3 respectively minimising mortality rate. This method of nitrogen fertilization (T2) also significantly affected plant-1stem biomass, plant-1tiller number, total chlorophyll, and soluble sugar concentrations before and after flooding. Based on these findings we proposed that application of lower dose of N (30kg/ha) as basal and rest amount of N in three split doses along with P and K (40kg/ha) in the field might be exploited to improve submergence tolerance and to obtain higher yield under flood prone ecosystem due to higher survival after de submergence corresponding to less post oxidative damage through proper N management during before and post submergence period.
Comparing multifunctional viral and eukaryotic proteins for generating scission necks in membranes
Authors: Alimohamadi Haleh , Luo Elizabeth Wei-Chia , Gupta Shivam , de Anda Jaime , Yang Rena , Mandal Taraknath , Wong Gerard C. L. 
Published: January 2024

AbstractDeterministic formation of membrane scission necks by protein machinery with multiplexed functions is critical in biology. A microbial example is the M2 viroporin, a proton pump from the influenza A virus which is multiplexed with membrane remodeling activity to induce budding and scission in the host membrane during viral maturation. In comparison, the dynamin family constitutes a class of eukaryotic proteins implicated in mitochondrial fission, as well as various budding and endocytosis pathways. In the case of Dnm1, the mitochondrial fission protein in yeast, the membrane remodeling activity is multiplexed with mechanoenzyme activity to create fission necks. It is not clear why these functions are combined in these scission processes, which occur in drastically different compositions and solution conditions. In general, direct experimental access to changing neck sizes induced by individual proteins or peptide fragments is challenging due to the nanoscale dimensions and influence of thermal fluctuations. Here, we use a mechanical model to estimate the size of scission necks by leveraging Small-Angle X-ray Scattering (SAXS) structural data of protein-lipid systems under different conditions. The influence of interfacial tension, lipid composition, and membrane budding morphology on the size of the induced scission necks is systematically investigated using our data and molecular dynamic simulations. We find that the M2 budding protein from the influenza A virus has robust pH-dependent membrane activity that induces nanoscopic necks within the range of spontaneous hemi-fission for a broad range of lipid compositions. In contrast, the sizes of scission necks generated by mitochondrial fission proteins strongly depend on lipid composition, which suggests a role for mechanical constriction.
From Understudied to Understood: Multi-Omics Analysis with MiniENCODE Exemplified by Zebrafish
Authors: Yang Hang , Shan Zhaojun , Shang Hanqiao , Jiang Puxuan , Li Yingshu , Tu Qiang 
Published: January 2024

AbstractThe ENCODE project provides a comprehensive map of genomic activity in humans and mice. However, its extensive toolbox can be too costly and technically challenging for smaller research communities. This presents a hurdle for understudied model organisms where resource constraints and complex omics data integration further compound the challenge. To bridge this gap, our study introduces a miniENCODE project, using the zebrafish as an exemplar. We collected, generated and integrated datasets from three experimental assays across developmental stages and adult tissues. This analysis is facilitated by our newly developed miniODP database, a computational tool designed for the integration and visualization of multiomics data. Utilizing these methods, we have cataloged over 52,000 candidate enhancers, identified various stage-specific, tissue-specific, and constantly active enhancers, and experimentally validated a subset of heart-specific enhancers. We have delineated key transcription factors and their corresponding regulatory networks across developmental stages and adult tissues. This study not only delivers valuable regulatory insights for the zebrafish research community but also illustrates how an integrative approach can aid in understanding complex regulatory mechanisms even with limited resources. This strategy could empower scientific communities working with various understudied model organisms to expedite their genomic research without overstretching their resources.
Understanding feeding competition under laboratory conditions: Rohu (Labeo rohita)versus Amazon sailfin catfish (Pterygoplichthysspp.)
Authors: Mallick Suman , Sundaray Jitendra Kumar , Ghosal Ratna 
Published: January 2024

AbstractCompetitive interactions between species is widely prevalent within the animal world. In this manuscript, we attempted to understand feeding competitions between the Amazon sailfin catfish, an invasive species introduced globally, and rohu, a keystone species native to several countries within southeast Asia. We used two different size classes of each species, large-size having total length (TL, from snout tip to caudal fin) of 15-20 cm and fingerling having TL <6 cm, and feeding duration was used as a proxy to understand competition. Our results demonstrated that feeding durations of large-size rohu were either similar or significantly (P<0.05) higher in presence of catfish when compared to trials in presence of conspecifics, indicating that large-size rohu is not a weak competitor. However, feeding durations of fingerling rohu was significantly (P<0.05) reduced in presence of both large-size and fingerling catfish, when compared to trials in presence of conspecifics. Moreover, fingerling rohu also displayed freeze (alarm) behavior in presence of the catfish. Interestingly, presence of rohu had no significant (P>0.05) impact on feeding durations of catfish. Overall, the study demonstrated that invasive catfish may behaviorally outcompete fingerling rohu, thus, threatening the sustenance of a species that is native to several freshwaters around the globe.