bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vagal nerve stimulation for headache
Authors: Venkatakrishnan Srikant , Thomas Pravin 
Published: November 2023

Purpose of review
Vagal nerve stimulation (VNS) is emerging as a probable therapeutic option for headache. Several questions remain on the mechanism of action, device parameters, efficacy, duration of treatment and long-term safety. This review aims at describing findings of recent literature pertaining to VNS for headache, to put these findings into the perspective of our current fund of knowledge and future scope of work on the topic.

Recent findings
Several studies on functional magnetic resonance imaging patterns following VNS in patients with headache have been published, revealing potential biomarkers of headache and possible treatment effects. A study on post-COVID-19 headache and its management with noninvasive cervical VNS adds to the body of original studies. Meta-analyses and systematic reviews outlining previous work have been published. The collection of these studies adds some data to mechanisms of VNS without adding much insight to differential effects of sub-types of VNS and possible device settings that could prove to be beneficial for headache management.

Summary
Well designed studies are needed to identify mechanisms of action, elicit differential effects of various stimulation parameters, and to demonstrate long-term therapeutic effects and safety of VNS in headache.
Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure
Authors: Yang Sijie , Yu Yuanling , Xu Yanli , Jian Fanchong , Song Weiliang , Yisimayi Ayijiang , Wang Peng , Wang Jing , Liu Jingyi , Yu Lingling , Niu Xiao , Wang Jing , Wang Yao , Shao Fei , Jin Ronghua , Wang Youchun , Cao Yunlong 
Published: November 2023

AbstractWhile the BA.2.86 variant demonstrated significant antigenic drift and enhanced ACE2 binding affinity, its ability to evade humoral immunity was relatively moderate compared to dominant strains like EG.5 and HK.3. However, the emergence of a new subvariant, JN.1 (BA.2.86.1.1), which possesses an additional spike mutation, L455S, compared to BA.2.86, showed a markedly increased prevalence in Europe and North America, especially in France. Here, we found that L455S of JN.1 significantly enhances immune evasion capabilities at the expense of reduced ACE2 binding affinity. This mutation enables JN.1 to effectively evade Class 1 neutralizing antibodies, offsetting BA.2.86’s susceptibility and thus allowing it to outcompete both its precursor BA.2.86 and the prevailing variants HV.1 (XBB.1.5+L452R+F456L) and JD.1.1 (XBB.1.5+L455F+F456L+A475V) in terms of humoral immune evasion. The rapid evolution from BA.2.86 to JN.1, similar to the earlier transition from BA.2.75 to CH.1.1, highlights the importance of closely monitoring strains with high ACE2 binding affinity and distinct antigenicity, despite their temporarily unremarkable immune evasion capabilities. Such strains could survive and transmit at low levels, since their large antigenic distance to dominant strains allow them to target distinct populations and accumulate immune-evasive mutations rapidly, often at the cost of receptor binding affinity.
Phylogenetic and protein structure analyses provide insight into the evolution and diversification of the CD36 domain ‘apex’ among scavenger receptor class B proteins across Eukarya
Authors: Boohar Reed T. , Vandepas Lauren E. , Traylor-Knowles Nikki , Browne William E. 
Published: November 2023

AbstractThe cluster of differentiation 36 (CD36) domain defines the characteristic ectodomain associated with scavenger receptor class B (SR-B) proteins. In bilaterians, SR-Bs play critical roles in diverse biological processes including innate immunity functions such as pathogen recognition and apoptotic cell clearance, as well as metabolic sensing associated with fatty acid uptake and cholesterol transport. While previous studies suggest this protein family is ancient, SR-B diversity across Eukarya has not been robustly characterized. We analyzed SR-B homologs identified from the genomes and transcriptomes of 165 diverse eukaryotic species. The presence of highly conserved amino acid motifs across major eukaryotic supergroups supports the presence of a SR-B homolog in the last eukaryotic common ancestor (LECA). Our comparative analyses of SR-B protein structure identifies the retention of a canonical asymmetric beta barrel tertiary structure within the CD36 ectodomain across Eukarya. We also identify multiple instances of independent lineage-specific sequence expansions in the apex region of the CD36 ectodomain — a region functionally associated with ligand-sensing. We hypothesize that a combination of both sequence expansion and structural variation in the CD36 apex region may reflect the evolution of SR-B ligand sensing specificity between diverse eukaryotic clades.Significance StatementSR-Bs are well-described in bilaterians, however the diversity and evolution of this ancient receptor protein family is poorly understood across Eukarya. Our analyses reveal a conserved beta barrel tertiary structure across eukaryotic SR-Bs that correlates with the presence of an intramolecular tunnel. In contrast, the putative ligand-sensing region associated with the apex of the protein can be highly divergent in both sequence and structure within and between taxa. Our data confirm the antiquity of the SR-B receptor protein family in Eukaryota and improve characterization of SR-B diversity outside of Metazoa. We hypothesize that eukaryotic SR-B diversity may be used as a model to explore receptor protein evolution driven by lineage-specific ligand specificity.
Cholinergic mu-opioid receptor deletion alters reward preference and aversion-resistance
Authors: Beane Cambria R. , Lewis Delainey G. , VI Nicolaus Bruns , Pikus Kat L. , Durfee Mary H. , Zegarelli Roman A. , Perry Thomas W. , Sandoval Oscar , Radke Anna K. 
Published: November 2023

AbstractHeavy alcohol use and binge drinking are important contributors to alcohol use disorder (AUD). The endogenous opioid system has been implicated in alcohol consumption and preference in both humans and animals. The mu opioid receptor (MOR) is expressed on multiple cells in the striatum, however little is known about the contributions of specific MOR populations to alcohol drinking behaviors. The current study used mice with a genetic deletion of MOR in cholinergic cells (ChAT- Cre/Oprm1fl/fl) to examine the role of MORs expressed in cholinergic interneurons (CINs) in home cage self-administration paradigms. Male and female ChAT-Cre/Oprm1fl/flmice were generated and heterozygous Cre+ (knockout) and Cre- (control) mice were tested for alcohol and nicotine consumption. In Experiment 1, binge-like and quinine-resistant drinking was tested using 15% ethanol (EtOH) in a two- bottle, limited-access Drinking in the Dark paradigm. Experiment 2 involved a six-week intermittent access paradigm in which mice received 20% EtOH, nicotine, and then a combination of the two drugs.Experiment 3 assessed locomotor activity, sucrose preference, and quinine sensitivity. Deleting MORs in cholinergic cells did not alter consumption of EtOH in Experiment 1 or 2. In Experiment 1, the MOR deletion resulted in greater consumption of quinine-adulterated EtOH in male Cre+ mice (vs. Cre-). In Experiment 2, Cre+ mice demonstrated a significantly lower preference for nicotine but did not differ from Cre- mice in nicotine or nicotine + EtOH consumption. Overall fluid consumption was also heightened in the Cre+ mice. In Experiment 3, Cre+ females were found to have greater locomotor activity and preference for sucrose vs. Cre- mice. These data suggest that cholinergic MORs are not required for EtOH, drinking behaviors but may contribute to aversion resistant EtOH drinking in a sex- dependent manner.
Mutation Impact on mRNA Versus Protein Expression across Human Cancers
Authors: Liu Yuqi , Elmas Abdulkadir , Huang Kuan-lin 
Published: November 2023

ABSTRACTCancer mutations are often assumed to alter proteins, thus promoting tumorigenesis. However, how mutations affect protein expression has rarely been systematically investigated. We conduct a comprehensive analysis of mutation impacts on mRNA- and protein-level expressions of 953 cancer cases with paired genomics and global proteomic profiling across six cancer types. Protein-level impacts are validated for 47.2% of the somatic expression quantitative trait loci (seQTLs), including mutations from likely “long-tail” driver genes. Devising a statistical pipeline for identifying somatic protein-specific QTLs (spsQTLs), we reveal several gene mutations, includingNF1andMAP2K4truncations andTP53missenses showing disproportional influence on protein abundance not readily explained by transcriptomics. Cross-validating with data from massively parallel assays of variant effects (MAVE),TP53missenses associated with high tumor TP53 proteins were experimentally confirmed as functional. Our study demonstrates the importance of considering protein-level expression to validate mutation impacts and identify functional genes and mutations.
High-sensitivity whole-genome recovery of single viral species in environmental samples
Authors: Chen Liyin , Chen Anqi , Zhang Xinge Diana , T. Robles Maria Saenz , Han Hee-Sun , Xiao Yi , Xiao Gao , Pipas James M. , Weitz David A. 
Published: November 2023

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. This work presents a method for reliably recovering complete viral genomes from complex environmental samples. Individual genomes are encapsulated into droplets and amplified using multiple displacement amplification. A novel gene detection assay, which employs an RNA-based probe and an exonuclease, selectively identifies droplets containing the target viral genome. Labeled droplets are sorted using a microfluidic sorter, and genomes are extracted for sequencing. Validation experiments using a sewage sample spiked with two known viruses demonstrate the method’s efficacy. We achieve 100% recovery of the spiked-in SV40 (Simian virus 40, 5243bp) genome sequence with uniform coverage distribution, and approximately 99.4% for the larger HAd5 genome (Human Adenovirus 5, 35938bp).Notably, genome recovery is achieved with as few as one sorted droplet, which enables the recovery of any desired genomes in complex environmental samples, regardless of their abundance. This method enables targeted characterizations of rare viral species and whole-genome amplification of single genomes for accessing the mutational profile in single virus genomes, contributing to an improved understanding of viral ecology.
Causal interpretations of family GWAS in the presence of heterogeneous effects
Authors: Veller Carl , Przeworski Molly , Coop Graham 
Published: November 2023

AbstractFamily-based genome-wide association studies (GWAS) have emerged as a gold standard for assessing causal effects of alleles and polygenic scores. Notably, family studies are often claimed to provide an unbiased estimate of the average causal effect (or average treatment effect; ATE) of an allele, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. Here, we show that this interpretation does not hold in general. Because Mendelian segregation only randomizes alleles among children of heterozygotes, the effects of alleles in the children of homozygotes are not observable. Consequently, if an allele has different average effects in the children of homozygotes and heterozygotes, as can arise in the presence of gene-by-environment interactions, gene-by-gene interactions, or differences in LD patterns, family studies provide a biased estimate of the average effect in the sample. At a single locus, family-based association studies can be thought of as providing an unbiased estimate of the average effect in the children of heterozygotes (i.e., a local average treatment effect; LATE). This interpretation does not extend to polygenic scores, however, because different sets of SNPs are heterozygous in each family. Therefore, other than under specific conditions, the within-family regression slope of a PGS cannot be assumed to provide an un-biased estimate for any subset or weighted average of families. Instead, family-based studies can be reinterpreted as enabling an unbiased estimate of the extent to which Mendelian segregation at loci in the PGS contributes to the population-level variance in the trait. Because this estimate does not include the between-family variance, however, this interpretation applies to only (roughly) half of the sample PGS variance. In practice, the potential biases of a family-based GWAS are likely smaller than those arising from confounding in a standard, population-based GWAS, and so family studies remain important for the dissection of genetic contributions to phenotypic variation. Nonetheless, the causal interpretation of family-based GWAS estimates is less straightforward than has been widely appreciated.
Xanthomonas citri subsp. citri type III effector PthA4 directs the dynamical expression of a putative citrus carbohydrate-binding protein gene for canker formation
Authors: Chen Xinyu , Zou Huasong , Zhuo Tao , Rou Wei , Wu Wei , Fan Xiaojing 
Published: November 2023

AbstractXanthomonas citrisubsp.citri(Xcc), the causal agent of citrus canker, elicits canker symptoms in citrus plants because of the transcriptional activator-like (TAL) effector PthA4, which activates the expression of the citrus susceptibility geneCsLOB1. This study reports the regulation of the putative carbohydrate-binding protein geneCs9g12620by PthA4-mediated induction of CsLOB1 duringXccinfection. We found that the transcription ofCs9g12620was induced by infection withXccin a PthA4-dependent manner. Even though it specifically bound to a putative TAL effector-binding element in theCs9g12620promoter, PthA4 exerted a suppressive effect on the promoter activity. In contrast, CsLOB1 bound to theCs9g12620promoter to activate its expression. The silencing ofCsLOB1significantly reduced the level of expression ofCs9g12620, which demonstrated thatCs9g12620was directly regulated by CsLOB1. Intriguingly, PhtA4 interacted with CsLOB1 and exerted feedback control that suppressed the induction of expression ofCs9g12620by CsLOB1. Transient overexpression and gene silencing revealed thatCs9g12620was required for the optimal development of canker symptoms. These results support the hypothesis that the expression ofCs9g12620is dynamically directed by PthA4 for canker formation through the PthA4-mediated induction of CsLOB1.
Latitudinal gradients in predation persist in urban environments
Authors: Hargreaves Anna L , Ensing John , Rahn Olivia , Oliveira Fernanda M. P. , Burkiewicz Jérôme , Lafond Joëlle , Haeussler Sybille , Byerley-Best M. Brooke , Lazda Kira , Slinn Heather L. , Martin Ella , Carlson Matthew L. , Sformo Todd L. , Dawson-Glass Emma , Chiuffo Mariana C. , Vargas-Rodriguez Yalma L. , García-Jiménez Carlos I. , Gomes Inácio J. M. T. , Klemet-N’Guessan Sandra , Paolucci Lucas , Joly Simon , Mehltreter Klaus , Muñoz Jenny , Buono Carmela , Brodie Jedediah F. , Rodriguez-Campbell Antonio , Veen Thor , Freeman Ben , Lee-Yaw Julie , Muñoz Juan Camilo , Paquette Alexandra , Butler Jennifer , Suaréz Esteban 
Published: November 2023

AbstractUrbanization can profoundly disrupt local ecology. But while urban areas now stretch across latitudes, little is known about urbanization’s effects on macroecological patterns. We used standardized experiments to test whether urbanization disrupts latitudinal gradients in seed predation, a macroecological pattern that shapes community assembly and diversity. Using >56,000 seeds, we compared predation in urbanized and natural areas across 14,000 km of latitude, spanning the Americas. Predation increased 5-fold from high latitudes to the tropics, and latitudinal gradients in predation persisted in urban areas despite significant habitat modification. Urbanization reduced predation by vertebrates, but not invertebrates, and seemed to increase ant predation specifically. Our results show that macroecological patterns in predation intensity can persist in urbanized environments, even as urbanization alters the relative importance of predators.One-Sentence SummaryAcross 56,000 seeds and 112° of latitude, latitudinal gradients in seed predation are equally strong in natural vs. urban areas
Reproducible Neuronal Components found using Group Independent Component Analysis in Resting State Electroencephalographic Data
Authors: Ochoa-Gómez John Fredy , Mantilla-Ramos Yorguin-José , Isaza Verónica Henao , Tobón Carlos Andrés , Lopera Francisco , Aguillón David , Suárez Jazmín Ximena 
Published: November 2023

AbstractObjectiveEvaluate the reliability of neural components obtained from the appli-cation of the group ICA (gICA) methodology to resting-state EEG datasets acquired from multiple sites.MethodsFive databases from three sites, covering a total of 292 healthy subjects, were analyzed. Each dataset was segmented into groups of 15 subjects, for a total of 19 groups. Data were pre-processed using an automatic pipeline leveraging robust average referencing, wavelet-ICA and automatic rejection of epochs. On each group, stable gICA decompositions were calculated using the ICASSO methodology through a range of orders of decompositions. Each order was characterized by reliability and neuralness metrics, which were evaluated to select a single order of decomposition. Finally, using the decompositions of the selected order, a clustering analysis was performed to find the common components across the 19 groups. Each cluster was characterized by the mean scalp map, its dipole generator with its localization in Talairach coordinates, the spectral behavior of the associated time-series of the components, the assigned ICLabel class and metrics that reflected their reproducibility.ResultsLower order of decompositions benefits the gICA methodology. At this, using an order of ten, the number of reproducible components with high neuronal information tends to be around nine. Of these, the bilateral motor, frontal medial, and occipital neuronal components were the most reproducible across the different datasets, appearing in more than 89% of the 19 groups evaluated.ConclusionWe developed a workflow that allows finding reproducible spatial filters between different data sets. This contributes to the improvement of the spatial resolution of the EEG as a brain mapping technique.
Perigestational Opioid Exposure Alters Alcohol-Driven Reward Behaviors in Adolescent Rats
Authors: Searles Christopher T. , Harder Hannah J. , Vogt Meghan E. , Murphy Anne Z. 
Published: November 2023

AbstractEvery fifteen minutes, a baby is born in the U.S. experiencing neonatal opioid withdrawal syndrome (NOWS). Since 2004, the rate of NOWS has increased 7-fold. Clinical studies have established intrauterine exposure to drugs of abuse as a risk factor for adverse health outcomes in adult life, including the propensity for future illicit drug use. Despite extensive knowledge about common mechanisms of action in the neural circuitry that drives opioid and alcohol reward, there is little data on the risks that those born with NOWS face regarding alcohol use later in life. Here, we investigate the impact of perigestational opioid exposure (POE) on the mesolimbic reward system of male and female Sprague Dawley rats at postnatal and adolescent ages. Our laboratory has developed a clinically relevant model for morphine exposure spanning pre-conception to the first week of life. Using this model, we found that POE increased alcohol consumption in female rats under noncontingent conditions, and inversely, reduced alcohol consumption in both male and female rats during operant conditioning sessions. Operant responding was also reduced for sucrose, suggesting that the impact of POE on reward-seeking behaviors is not limited to drugs of abuse. Expression of µ-opioid receptors was also significantly altered in the nucleus accumbens and medial habenula, regions previously shown to play a significant role in reward/aversion circuitry.Significance StatementEarly life exposure to opioids is known to alter future drug behavior in rats. In the present study, female rats exposed to morphine via their mothers throughout and after pregnancy exhibited increased alcohol consumption when allowed to consume freely. During operant conditioning, however, male and female rats exposed to gestational morphine decreased consumption of alcohol as well as sucrose. We also observed that gestational morphine exposure altered µ-opioid receptor expression in reward-related brain regions. Our study provides the first evidence of changes in alcohol-directed reward behavior in a gestational opioid exposure rat model.
Injectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and generate neuroprotection in the SOD1G93Amouse model of ALS via activation of the IGF–Akt–mTOR axis pathway
Authors: Rodriguez-Romano Ana , Gonzalez-Valdivieso Juan , Moreno-Martinez Laura , Costa Juan Francisco Vázquez , Osta Rosario , Rico Patricia 
Published: November 2023

AbstractAmyotrophic Lateral Sclerosis (ALS) is the most frequent and fatal condition that causes motor neuron loss and skeletal muscle paralysis. Although ALS is associated with mutations in over 40 genes, its etiology remains largely elusive without a cure or effective treatment. Historically considered the prototype of motor neuron diseases, ALS is defined today as a multisystem disorder that presents several changes in non-neuronal cell types, such as pathological changes in muscle occurring before disease onset and independent from motor neuron degeneration (dying back hypothesis). We base on the hypothesis that skeletal muscle may have an active contribution to disease pathology and thus we consider skeletal muscle tissue as a therapeutic target for ALS.In previous works, we have demonstrated that boron transporter NaBC1 (encoded by theSLC4A11gene), after activation co-localizes with integrins and growth factor receptors producing a functional cluster that synergistically enhances crosstalk mechanisms accelerating muscle repair. In this work, we aimed to study the effects of borax (B) in a SOD1 mouse model of ALS targeting muscle. We have engineered and characterized injectable alginate-based hydrogels with controlled local borax release to effectively activate muscle NaBC1in vivo. Treated mice presented improved motor function and extended survival correlated with the activation of essential muscle metabolic pathways, resulting in an enhanced muscle repair response and reduced muscle atrophy and inflammation. Interestingly, the activation of muscle repair mechanisms at the local level produced retrograde neuroprotection by motor neuron preservation and reduction in neuroinflammation. Altogether, this work presents evidence supporting the involvement of muscle tissue in ALS pathology, reinforcing skeletal muscle as a primary target to develop new therapies for ALS. We propose a novel strategy based on NaBC1 activation for ALS muscle regeneration.Graphical abstract