bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informing Extinction Risk: Summarizing Population Viability through a Meta-analysis of Multiple Long-term Monitoring Programs for a Declining Estuarine Fish Species
Authors: Tobias Vanessa D. , Chen Ernest , Hobbs James , Eakin Michael , Detwiler Steven 
Published: April 2023

AbstractDecisions about whether to designate a species for conservation and protection depend on the ability to summarize their population trajectories and their risk of extinction. Such decisions may rely on quantitative population viability analyses based on a time series of abundance index values that are derived from a monitoring program. In the case of the Longfin Smelt (Spirinchus thaleichthys), a decision to protect a distinct population segment of the species under the U.S. Endangered Species Act was informed by several indices of population abundance. In this paper, we combined individual population viability analyses into a single metric for extinction risk using a meta-analysis framework. Individual monitoring surveys for this species generally agreed that the trajectory of abundance was downward and combining data from all of the surveys produced a better summary of the population growth rate. We also used the population growth rates in a simulation to estimate the probability that the abundance of Longfin Smelt dropped too low to recover. We found that this probability of quasi-extinction was substantial, exceeding 20% over two decades. This study demonstrates a practical way that having multiple sources of information creates better information about the trajectory of a population. Individually, the surveys contribute information about specific life stages or ages to our understanding of the population. Combined into one metric and an associated graphical summary, this analysis succinctly communicates risk and creates a benchmark for evaluating future management decisions.
Anticipatory Biogenesis of Hepatic Fed MicroRNAs is Regulated by Metabolic and Circadian Inputs
Authors: Sandra U.S. , Chowdhury Shreyam , Kolthur-Seetharam Ullas 
Published: April 2023

ABSTRACTStarvation and refeeding are mostly unanticipated in the wild in terms of duration, frequency, and nutritional value of the refed state. Notwithstanding this, organisms mount efficient and reproducible responses to restore metabolic homeostasis. Hence, it is intuitive to invoke expectant molecular mechanisms that build anticipatory responses to enable physiological toggling during fed-fast cycles. In this regard, we report anticipatory biogenesis of oscillatory hepatic microRNAs, which were earlier shown to peak during a fed state to inhibit starvation-responsive genes. Results presented in this study clearly demonstrate that the levels of primary and precursor microRNA transcripts increase during a fasting state, in anticipation of a fed response. We delineate the importance of both metabolic inputs and circadian cues in orchestrating microRNA homeostasis in a physiological setting, using the most prominent hepatic fed-miRNAs as candidates. Besides illustrating the metabo-endocrine control, our findings provide a mechanistic basis for the overarching influence of starvation on anticipatory biogenesis. Importantly, by employing pharmacological agents that are widely used in the clinics, we point out the high potential of interventions to restore homeostasis of hepatic microRNAs, whose deregulated expression is otherwise well established to cause metabolic diseases.
A novel simian adenovirus vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens
Authors: Zhang Panli , Luo Shengxue , Zou Peng , Deng Qitao , Wang Cong , Li Jinfeng , Cai Peiqiao , Zhang Ling , Li Chengyao , Li Tingting 
Published: April 2023

ABSTRACTThe failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus vectored COVID-19 vaccine (Sad23L- nCoV-S) in mice in comparison with Ad5-nCoV-S by intranasal (IN) drip and intramuscular (IM) injection vaccinations. As good as the well-known Ad5-nCoV-S vaccine, a single-dose IN inoculation of 1×109PFU Sad23L-nCoV-S vaccine induced a similar level of IgG S-binding antibody (S-BAb) and neutralizing antibody (NAb) and higher IgA in serum, while IN route raised significantly higher IgG and IgA S- BAb and NAb in bronchoalveolar lavage (BAL), and specific IFN-γ secreting T cell response in lung compared with IM route, but lower T cell response in spleen. By prime-boost vaccination regimens with different combination of IN and IM inoculations of Sad23L-nCoV-S vaccine, the IN involved vaccinations stimulated higher protective mucosal or local immunity in BAL and lung, while the IM involved immunizations induced higher systemic immunity in serum and spleen. A long-term sustained systemic and mucosal NAb and T cell immunity to SARS-CoV-2 was maintained at high levels over 32 weeks by prime-boost vaccination regimens with IN and IM routes. In conclusion, priming or boosting immunization with IN inoculation of Sad23L-nCoV-S vaccine could induced effective mucosal immunity and in combination of IM route could additionally achieve systemic immunity, which provided an important reference for vaccination regimens against respiratory virus infection.IMPORTANCEThe essential goal of vaccination is to generate potent and long-term protection against diseases. Several factors including type of vector, delivery route, boosting regimen influence the outcome of prime-boost immunization approaches. The immunization regimen by constructing a novel simian adenovirus vectored COVID-19 vaccine and employing combination of intranasal and intramuscular inoculations, could elicit mucosal neutralizing antibodies against five mutant strains in the respiratory tract, and strong systemic immunity. Immune protection could last for more than 32 weeks. Vectored vaccine construction and immunization regimens have positively impacted respiratory disease prevention.
Do glucocorticoids indicate stress? Meta-analysis reveals a tight association between glucocorticoids and metabolic rate
Authors: Jimeno Blanca , Verhulst Simon 
Published: April 2023

ABSTRACTGlucocorticoid (GC) variation has long been thought to reflect variation in organismal ‘stress’, but associations between GCs and Darwinian fitness components are diverse in magnitude, direction, and highly context-dependent. This paradox reveals our poor understanding of the causes of GC variation, contrasting with the detailed knowledge of the functional consequences of GC variation. Amongst an array of effects in many physiological systems, GCs orchestrate energy availability to anticipate and recover from predictable and unpredictable environmental fluctuations and challenges. Although this is mechanistically well-known, the extent to which GC levels are quantitatively explained by energy metabolism is unresolved. We investigated this association through meta-analysis, selecting studies of endotherms in which (1) an experiment was performed that affected metabolic rate and (2) metabolic rate and GC-levels were measured simultaneously. We found that an increase in metabolic rate was associated with an increase in GC levels in 20 out of 21 studies (32 out of 35 effect sizes). More importantly, there was a strong positive correlation between the increases in metabolic rate and GCs (p=0.003). This pattern was similar in birds and mammals, and independent of the nature of the experimental treatment. We conclude that metabolic rate is a major driver of GC variation within individuals. Stressors often affect metabolic rate, leading us to question whether GC levels provide information on ‘stress’ beyond the stressor’s effect on metabolic rate.
Spatial phylogenetics of Fagales: Investigating the history of temperate forests
Authors: Folk R.A. , Siniscalchi C.M. , Doby J. , Kates H.R. , Manchester S.R. , Soltis P.S. , Soltis D.E. , Guralnick R.P. , Belitz M. 
Published: April 2023

AimQuantifying the phylogenetic diversity of temperate trees is essential for understanding what processes are implicated in shaping the modern distribution of temperate broadleaf forest and other major forest biomes. Here we focus on Fagales, an iconic member of forests worldwide, to uncover global diversity and endemism patterns and investigate potential drivers responsible for the spatial distribution of fagalean forest communities.LocationGlobal.TaxonFagales.MethodsWe combined phylogenetic data covering 60.2% of living species, fine-scale distribution models covering 90% of species, and nodulation data covering all species to investigate the distribution of species richness at fine spatial scales and compare this to relative phylogenetic diversity (RPD) and phylogenetic endemism. Further, we quantify phylogenetic betadiversity and bioregionalization of Fagales and determine hotspots of Fagales species engaging in root nodule symbiosis (RNS) with nitrogen-fixing actinomycetes.ResultsWe find the highest richness in temperate east Asia, eastern North America, and equatorial montane regions of Asia and Central America. By contrast, RPD is highest at higher latitudes, where RNS also predominates. We found a strong spatial structuring of regionalizations of Fagales floras as defined by phylogeny and traits related to RNS, reflecting distinct Northern and Southern Hemisphere floras (with the exception of a unique Afro-Boreal region) and highly distinct tropical montane communities.Main conclusionsSpecies richness and phylogenetic regionalization accord well with traditional biogeographic concepts for temperate forests, but RPD does not. This may reflect ecological filtering specific to Fagales, as RNS strategies are almost universal in the highest RPD regions. Our results highlight the importance of global-scale, clade-specific spatial phylogenetics and its utility for understanding the history behind temperate forest diversity.
PTPN1/2 inhibition induces highly functional terminal effector CD8 T cells through autocrine IL-10
Authors: Perez-Quintero Luis-Alberto , Poirier Alexandre , Martinez-Cordoba Zuzet , Feng Chu-Han , Aubry Isabelle , Carli Cedric , Kamyabiazar Samaneh , Pacis Alain , Zolotarov Yevgen , Pike Kelly-Anne , Delisle Jean-Sebastien , Tremblay Michel L. 
Published: April 2023

AbstractIncreased understanding of the modulatory pathways controlling CD8 T cell responses has led to the formulation of successful checkpoint inhibitor-based immunotherapies against cancer. However, their effectiveness is limited to a few tumor types, motivating the search for novel combinatorial strategies. PTPN1 and PTPN2 are two homologous protein tyrosine phosphatases recently proposed as potent intracellular checkpoints. Furthermore, their catalytic domain is a propitious target for small-molecule pharmacological intervention. Herein we investigated the potential effects of conditional genetic deletion of either or both phosphatases in mouse CD8 T cells, one of the main effectors in cancer immunotherapy. Our results demonstrated that hemizygous deletion of PTPN1 in a PTPN2 deficient background heightens the enhanced effector phenotype already observed in PTPN2 defective CD8 T cells. This functional gain is mediated by an autocrine IL-10 positive feedback loop. Pharmacological inhibition with a PTPN1/2 small-molecule inhibitor yielded similar results, highlighting the importance of simultaneously inhibiting both phosphatases. Our study uncovers a novel mechanism by which the downregulation of PTPN1 and PTPN2 act as a powerful tool for potentiating CD8 cytotoxic responses.
RGS6 mediates exercise-induced recovery of hippocampal neurogenesis, learning, and memory in an Alzheimer’s mouse model
Authors: Spicer Mackenzie M. , Yang Jianqi , Fu Daniel , DeVore Alison N. , Lauffer Marisol , Atasoy Nilufer S. , Atasoy Deniz , Fisher Rory A. 
Published: April 2023

AbstractHippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease (AD). Adult hippocampal neurogenesis (AHN) is reduced in AD patients. Exercise stimulates AHN in rodents and improves memory and slows cognitive decline in AD patients. However, the molecular pathways for exercise-induced AHN and improved cognition in AD are poorly understood. Here, we show that voluntary running in APPSWEmice restores their hippocampal cognitive impairments to that of control mice. This cognitive rescue was abolished by RGS6 deletion in dentate gyrus (DG) neuronal progenitors (NPs), which also abolished running-mediated increases in AHN. AHN was reduced in sedentary APPSWEmice versus control mice, with basal AHN reduced by RGS6 deletion in DG NPs. RGS6 expression is significantly lower in the DG of AD patients. Thus, RGS6 mediates exercise-induced rescue of impaired cognition and AHN in AD mice, identifying RGS6 in DG NPs as a potential target to combat hippocampal neuron loss in AD.TeaserRGS6 expression in hippocampal NPCs promotes voluntary running-induced neurogenesis and restored cognition in APPSWEmice.Field CodesRGS6, Alzheimer’s disease, adult hippocampal neurogenesis, neural precursor cells, dentate gyrus, exercise, learning/memory
ER-dependent membrane repair of mycobacteria-induced vacuole damage
Authors: Anand Aby , Mazur Anna-Carina , Rosell-Arevalo Patricia , Franzkoch Rico , Breitsprecher Leonhard , Listian Stevanus A. , Hüttel Sylvana V. , Müller Danica , Schäfer Deise G. , Vormittag Simone , Hilbi Hubert , Maniak Markus , G. Gutierrez Maximiliano , Barisch Caroline 
Published: April 2023

AbstractSeveral intracellular pathogens, such asMycobacterium tuberculosis,damage endomembranes to access the cytosol and subvert innate immune responses. The host counteracts endomembrane damage by recruiting repair machineries that retain the pathogen inside the vacuole.Here, we show that the endoplasmic reticulum (ER)-Golgi protein oxysterol binding protein (OSBP) and itsDictyostelium discoideumhomologue OSBP8 are recruited to theMycobacterium-containing vacuole (MCV) after ESX-1-dependent membrane damage. Lack of OSBP8 causes a hyperaccumulation of phosphatidylinositol-4-phosphate (PI4P) on the MCV and decreased cell viability. OSBP8-depleted cells had reduced lysosomal and degradative capabilities of their vacuoles that favoured mycobacterial growth. In agreement with a function of OSBP8 in membrane repair, human macrophages infected withM. tuberculosisrecruited OSBP in an ESX-1 dependent manner. These findings identified an ER-dependent repair mechanism for restoring MCVs in which OSBP8 functions to equilibrate PI4P levels on damaged membranes.ImportanceTuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen.Mycobacterium tuberculosis, the causative agent, has perfected many ways to replicate and persist within its host. While mycobacteria induce vacuole damage to evade the toxic environment and eventually escape into the cytosol, the host recruits repair machineries to restore the MCV membrane. However, how lipids are delivered for membrane repair is poorly understood. Using advanced fluorescence imaging and volumetric correlative approaches, we demonstrate that this involves the recruitment of the ER-Golgi lipid transfer protein OSBP8 in theD. discoideum/M. marinumsystem. Strikingly, depletion of OSBP8 affects lysosomal function accelerating mycobacterial growth. This indicates that an ER-dependent repair pathway constitutes a host defence mechanism against intracellular pathogens such asM. tuberculosis.
Barley HvNIP2;1 aquaporin permeates water, metalloids, saccharides, and ion pairs due to structural plasticity and diversification
Authors: Venkataraghavan Akshayaa , Kim Hoshin , Schwerdt Julian G. , Gulyuk Alexey V. , Singh Abhishek , Yingling Yaroslava G. , Tyerman Stephen D. , Hrmova Maria 
Published: April 2023

AbstractAquaporins can facilitate the passive movement of water and small polar molecules and some ions. The barley Nodulin 26-like Intrinsic Protein (HvNIP2;1) embedded in liposomes and examined through stopped-flow light scattering spectrophotometry andXenopusoocyte swelling assays was found to permeate water, boric and germanic acids, sucrose and L-arabinose but not D-glucose or D-fructose. Other saccharides, such as neutral (D-mannose, D-galactose, D-xylose, D-mannoheptaose) and charged (N-acetyl D-glucosamine, D-glucosamine, D-glucuronic acid) aldoses, disaccharides (lactose, cellobiose, gentiobiose, trehalose), trisaccharide raffinose, and urea, glycerol, and acyclic polyols were permeated to a much lower extent. Apparent permeation of hydrated KCl and MgSO4ion pairs was observed, while CH3COONa and NaNO3permeated at significantly lower rates. Experiments with boric acid and sucrose revealed no apparent interaction between solutes when permeated together, and AgNO3blocked the permeation of all solutes. Full-scale steered molecular dynamics simulations of HvNIP2;1 and spinach SoPIP2;1 revealed possible rectification for water, boric acid, and sucrose transport, and defined key residues interacting with permeants. In a biological context, the simulated sucrose rectification could mediate its apoplastic-to-intracellular transport but not the reverse, thus, constituting a novel element of plant saccharide-transporting machinery. Phylogenomic analyses of 164 Viridiplantae and 2,993 Archaean, bacterial, fungal, and Metazoan aquaporins rationalised solute poly-selectivity in NIP3 sub-clade entries and suggested that they diversified from other sub-clades to acquire a unique specificity of saccharide transporters. Solute specificity definition in NIP aquaporins could inspire developing plants for sustained food production.Significance StatementAquaporins are fundamental to water and solute movements in nearly all living organisms. Solute selectivity inspections of the HvNIP2;1 aquaporin revealed that it transported water, hydroxylated metalloids boric and germanic acids, sucrose, L-arabinose, KCl, and MgSO4ion pairs, but not D-glucose or D-fructose and to lesser extent urea, and acyclic polyols. This poly-selective transport by HvNIP2;1 classified in the NIP3 sub-clade aquaporins may afford nutritional and protective roles during plant development and in response to abiotic stresses. It is anticipated that the solute specificity definition of HvNIP2;1 inspires protein engineering and in silico mining to develop plants, which when exposed to suboptimal soil conditions of high soil metalloids, would overcome toxicity for sustained food production.
Cell Type-Specific Regulation by a Heptad of Transcription Factors in Human Hematopoietic Stem and Progenitor Cells
Authors: Subramanian Shruthi , Thoms Julie A.I. , Huang Yizhou , Cornejo Paola , Koch Forrest C. , Jacquelin Sebastien , Shen Sylvie , Song Emma , Joshi Swapna , Brownlee Chris , Woll Petter S. , Fajardo Diego Chacon , Beck Dominik , Curtis David J. , Yehson Kenneth , Antonenas Vicki , Brien Tracey O’ , Trickett Annette , Powell Jason A. , Lewis Ian D. , Pitson Stuart M. , Gandhi Maher K. , Lane Steven W. , Vafaee Fatemeh , Wong Emily S. , Göttgens Berthold , Rokny Hamid Alinejad , Wong Jason W.H , Pimanda John E. 
Published: April 2023

SummaryHematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay of transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs - FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2 - bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remained unknown. We mapped genome-wide chromatin contacts and TF binding profiles in HSPC subsets (HSC, CMP, GMP, MEP) and found that heptad occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type-specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell-specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. These findings suggest that specific heptad-TF combinations play critical roles in regulating hematopoietic differentiation and provide a valuable resource for development of targeted therapies to manipulate specific HSPC subsets.
Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain
Authors: Kroll Sara L. , Hulka Lea M. , Kexel Ann-Kathrin , Vonmoos Matthias , Preller Katrin H. , Treyer Valerie , Ametamey Simon M. , Baumgartner Markus R. , Boost Carola , Pahlisch Franziska , Rohleder Cathrin , Leweke F. Markus , Quednow Boris B. 
Published: April 2023

ABSTRACTAnimal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33; controls: N=43). In an additional analysis using11C-ABP688 positron emission tomography (PET) in a male subsample (CU: N=18; controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence.