bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational modeling of dorsal root ganglion stimulation using an Injectrode
Authors: Bhowmick Sauradeep , Graham Robert D. , Verma Nishant , Trevathan James K. , Franke Manfred , Nieuwoudt Stephan , Fisher Lee E. , Shoffstall Andrew J. , Weber Douglas J. , Ludwig Kip A. , Lempka Scott F. 
Published: September 2023

ABSTRACTObjectiveMinimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated platinum/iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, effectiveness of stimulation relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures.ApproachWe employed a hybrid computational modeling approach to analyze the impact of the Injectrode system design parameters on charge delivery and the neural response to stimulation. We constructed multiple finite element method models of DRG stimulation and multi-compartment models of DRG neurons. We simulated the neural responses using parameters based on prior acute preclinical experiments. Additionally, we developed multiple human-scale computational models of DRG stimulation to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds.Main resultsOur findings were in accordance with acute experimental measurements and indicated that the Injectrode system predominantly engages large-diameter afferents (Aβ-fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (Aδ-fibers) activity.SignificanceThe Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired Aβ activation from the undesired Aδ-fiber activation.
Effect of Tai Ji and/or Qigong on Patients with Stable Chronic Obstructive Pulmonary Disease A protocol for meta-analysis and systematic review
Authors: Liu Hongliang , Cheng Ningchang 
Published: September 2023

AbstractBackgroundChronic obstructive pulmonary disease (COPD) is a global health problem with high morbidity and mortality. Tai Ji and Qigong are traditional Chinese mediative movements, benefit COPD patient’s physical and mental health.MethodsWe searched the following twelve databases Web of Science, EBSCO, Medline, EMBASE, Scopus, PubMed, PsycArticles, Psychology and Behavioral Sciences Collection, PsycInfo, CINAHL, Cochrane Library online and Clinical trials from inception to July 2023. Any RCTs managed with Tai Ji and/or Qigong on stable COPD were eligible without age, publishment language and comparison management restrict. Outcome measures comprised pulmonary function, the incidence of acute exacerbation, 6WMD, chronic pain, physical and/or cognitive function, and any assessment of people QoL.ResultsOur research will update evidence summaries and provide a quantitative and standardized assessment of the effect of Tai Ji and/or Qigong on patients with stable COPD.ConclusionOur research will generate the latest evidence for determining whether Tai Ji and/or Qigong is equivalent to conventional PR.
Recognition of highly branched N-glycans of the porcine whipworm by the immune system
Authors: Eckmair Barbara , Gao Chao , Mehta Akul Y. , Dutkiewicz Zuzanna , Vanbeselaere Jorick , Cummings Richard D. , Paschinger Katharina , Wilson Iain B. H. 
Published: September 2023

AbstractGlycans are key to host-pathogen interactions, whereby recognition by the host and immunomodulation by the pathogen can be mediated by carbohydrate binding proteins, such as lectins of the innate immune system, and their glycoconjugate ligands. Previous studies have shown that excretory-secretory products of the porcine nematode parasiteTrichuris suisexert immunomodulatory effects in a glycan-dependent manner. To better understand the mechanisms of these interactions, we prepared N-glycans fromT. suisand both analyzed their structures and used them to generate a natural glycan microarray. With this array we explored the interactions of glycans with C-type lectins, C-reactive protein and sera fromT. suisinfected pigs. Glycans containing LacdiNAc and phosphorylcholine-modified glycans were associated with the highest binding by most of these proteins. In-depth analysis revealed not only fucosylated LacdiNAc motifs with and without phosphorylcholine moieties, but phosphorylcholine-modified mannose and N-acetylhexosamine-substituted fucose residues, in the context of maximally tetraantennary N-glycan scaffolds. Furthermore, O-glycans also contained fucosylated motifs. In summary, the glycans ofT. suisare recognized by both the innate and adaptive immune systems, and also exhibit species-specific features distinguishing its glycome from those of other nematodes.
Rapid and dynamic evolution of a giant Y chromosome inSilene latifolia
Authors: Akagi Takashi , Fujita Naoko , Masuda Kanae , Shirasawa Kenta , Nagaki Kiyotaka , Horiuchi Ayano , Kuwada Eriko , Kunou Riko , Nakamura Koki , Ikeda Yoko , Ushijima Koichiro , Charlesworth Deborah 
Published: September 2023

AbstractTo test hypotheses about the evolution of massive sex-linked regions in plants, we sequenced the genome ofSilene latifolia, whose giant heteromorphic sex chromosomes were first discovered in 1923. It has long been known that the Y consists mainly of a male-specific region which does not recombine with the X in male meiosis, and that this region carries the primary sex-determining genes, and other genes contributing to male functioning. However, only with a whole Y chromosome assembly can the candidates be validated experimentally, as we describe. Our new results also illuminate the genomic changes as the ancestral chromosome evolved into the current XY pair, testing ideas about why large regions of sex-linkage evolve, and the mechanisms creating the present recombination pattern.One sentence summaryBased on the whole genome sequences ofSilene latifolia, a model species for plant sex chromosome evolution, we describe discovery of genes underlying male-female flower differences, and relate the results to ideas about the evolution of the vast non-recombining regions of the Y chromosome.
Identification and targeting of microbial putrescine acetylation in bloodstream infections
Authors: Mayers Jared R. , Varon Jack , Zhou Ruixuan R. , Daniel-Ivad Martin , Beaulieu Courtney , Bholse Amrisha , Glasser Nathaniel R. , Lichtenauer Franziska M. , Ng Julie , Pinilla Vera Mayra , Huttenhower Curtis , Perrella Mark A. , Clish Clary B. , Zhao Sihai D. , Baron Rebecca M. , Balskus Emily P. 
Published: September 2023

SUMMARYThe growth of antimicrobial resistance (AMR) has highlighted an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe bacterial infections profoundly alter host metabolism, prior studies have largely ignored alterations in microbial metabolism in this context. Performing metabolomics on patient and mouse plasma samples, we identify elevated levels of bacterially-derivedN- acetylputrescine during gram-negative bloodstream infections (BSI), with higher levels associated with worse clinical outcomes. We discover that SpeG is the bacterial enzyme responsible for acetylating putrescine and show that blocking its activity reduces bacterial proliferation and slows pathogenesis. Reduction of SpeG activity enhances bacterial membrane permeability and results in increased intracellular accumulation of antibiotics, allowing us to overcome AMR of clinical isolates both in culture andin vivo.This study highlights how studying pathogen metabolism in the natural context of infection can reveal new therapeutic strategies for addressing challenging infections.
An ATF4-centric regulatory network is required for the assembly and function of the OXPHOS system
Authors: Cagin Umut , Gómez Manuel José , Casajús-Pelegay Ester , Nieto-Arellano Rocío , Arias-Sanroman Daniel , Movilla Nieves , Moreno-Loshuertos Raquel , Gallardo M. Esther , Sánchez-Cabo Fátima , Enriquez José Antonio 
Published: September 2023

ABSTRACTIdentifying the factors that determine mammalian cell viability when oxidative phosphorylation (OXPHOS) function is impaired poses challenges due to the diverse cellular responses and limited clinical material availability. Moreover, animal models often fail to replicate human phenotypes. To address these challenges, this study conducted comprehensive analyses involving multiple defects and species by comparing the RNA-Seq expression profiles of human and murine cell lines with distinct nuclear backgrounds, representing both normal and OXPHOS-deficient models. To minimize species-specific variation, the study employed clustering techniques to group murine genes affected by OXPHOS dysfunction and identified crucial regulators like ATF4, UCP1, and SYVN1. ATF4 consistently displayed activation in response to OXPHOS defects, not only in murine but also in human cells, confirming its pivotal role in the cellular response to mitochondrial dysfunction. By integrating human and murine data, the study unveiled a conserved regulatory network encompassing genes related to the mTOR pathway and folate metabolism. Remarkably, the study uncovered an unexpected finding: the depletion of ATF4 in both mouse and human cells impairs OXPHOS assembly and supercomplex organization. This impairment primarily stems from a severe disruption in complex I assembly in the absence of ATF4, even under non-stress conditions.
C. elegansDicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA
Authors: Consalvo Claudia D. , Aderounmu Adedeji M. , Donelick Helen M. , Aruscavage P. Joe , Eckert Debra M. , Shen Peter S. , Bass Brenda L. 
Published: September 2023

Abstract/SummaryInvertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense,C. elegansDicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1’s helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways.
Comparative dynamics of gene expression during in vitro and in vivoCandida albicansfilamentation
Authors: Wakade Rohan S. , Krysan Damian J. 
Published: September 2023

AbstractCandida albicansis one of them most common causes of fungal disease in humans and is a commensal member of the human microbiome. The ability ofC. albicansto cause disease is tightly correlated with its ability to undergo a morphological transition from budding yeast to a filamentous form (hyphae and pseudohyphae). This morphological transition is accompanied by the induction of a set of well characterized hyphae-associated genes and transcriptional regulators. To date, the vast majority of data regarding this process has been based on in vitro studies of filamentation using a range of inducing conditions. Recently, we developed an in vivo imaging approach that allows the direct characterization of morphological transition during mammalian infection. Here, we couple this imaging assay with in vivo expression profiling to characterize the time course of in vivo filamentation and the accompanying changes in gene expression. We also compare in vivo observations to in vitro filamentation using a medium (RPMI 1640 tissue culture medium with 10% bovine calf serum) widely used to mimic host conditions. From these data, we make the following conclusions regarding in vivo and in vitro filamentation. First, the transcriptional programs regulating filamentation are rapidly induced in vitro and in vivo. Second, the tempo of filamentation in vivo is prolonged relative to in vitro filamentation and the period of high expression of genes associated with that process is also prolonged. Third, hyphae are adapting to changing infection environments after filamentation has reached steady-state.ImportanceCandida albicansfilamentation is correlated with virulence and is an intensively studied aspect ofC. albicansbiology. The vast majority of studies onC. albicansfilamentation are based on in vitro induction of hyphae and pseudohyphae. Here we used an in vivo filamentation assay and in vivo expression profiling to compare the tempo of morphogenesis and gene expression between in vitro and in vivo filamentation. Although the hyphal gene expression profile is induced rapidly in both conditions, it remains stably expressed over the 24hr time course in vivo while the expression of other environmentally responsive genes is dynamic. As such, it is important to regard the filamentation process as a separate growth phase ofC. albicansthat is as adaptable to changing growth conditions as the more familiar yeast phase.
Bacteroides thetaiotaomicronmetabolic activity decreases with polysaccharide molecular weight
Authors: Wong Jeremy P. H. , Chillier Noémie , Fischer-Stettler Michaela , Zeeman Samuel C. , Battin Tom J. , Persat Alexandre 
Published: September 2023

AbstractThe human colon hosts hundreds of commensal bacterial species, many of which ferment complex dietary carbohydrates. To transform these fibers into metabolically-accessible compounds, microbes often express series of dedicated enzymes homologous to the starch utilization system (sus) encoded in polysaccharide utilization loci (PULs). The genome ofBacteroides thetaiotaomicron (Bt),a common member of the human gut microbiota, encodes nearly 100 PULs, conferring a strong metabolic versatility. While the structures and functions of individual enzymes within the PULs have been investigated, little is known about how polysaccharide complexity impacts the function of sus-like systems. We here show that the activity of sus-like systems depends on polysaccharide size, ultimately impacting bacterial growth. We demonstrate the effect of size-dependent metabolism in the context of dextran metabolism driven by the specific utilization system PUL48. We find that as molecular weight of dextran increases,Btgrowth rate decreases and lag time increases. At the enzymatic level, the dextranase BT3087 is the main glycosylhydrolase for dextran utilization and that BT3087 and BT3088 contribute toBtdextran metabolism in a size-dependent manner. Finally, we show that the polysaccharide size-dependent metabolism ofBtimpacts its metabolic output in a way that modulates the composition of a producer-consumer community it forms withBacteroides fragilis. Altogether, our results expose an overlooked aspect ofBtmetabolism which can impact the composition and diversity of microbiota.
GENOMES UNCOUPLED1: an RNA-binding protein required for early PSII biogenesis
Authors: Cui Chaojun , Sun Shuyi , Zhang Siyuan , Zhang Yu , Kim Chanhong 
Published: September 2023

AbstractGenomes Uncoupled1 (GUN1), a nuclear-encoded chloroplast pentatricopeptide repeat (PPR) protein, serves as a master integrator of diverse retrograde signals, mediating chloroplast-to-nucleus retrograde signaling. Although PPR proteins primarily function in organelle RNA metabolism, a target RNA of GUN1 remained unknown. This study reveals that GUN1 recognizespsbDtranscripts derived from a blue light-responsive promoter (BLRP), transcripts referred to aspsbDBLRP. Overexpression of GUN1 significantly reduces the levels ofpsbDBLRP, whereas the loss of GUN1 leads to the accumulation of the putative target RNA. Thein vitroRNA andin vivogenetic studies further demonstrate the critical role of the C-terminal small MutS-related (SMR) domain in stimulatingpsbDBLRP processing and PsbD (D2, a PSII core protein) synthesis. The GUN1-dependentpsbDBLRP processing promotes PSII biogenesis during the early seedling development and de-etiolation phase. This finding underscores the role of GUN1 as an RNA-binding protein, highlighting the essential function of the SMR domain in processing the target RNA.SignificanceBiogenic retrograde signaling is essential in regulating chloroplast biogenesis, and it entails a nuclear-encoded chloroplast protein, Genomes Uncoupled1 (GUN1). Since its initial discovery in 1993, thegun1mutant has been widely used to reveal the precise function of GUN1 in plastids as well as its downstream signaling components. Although GUN1 contains pentatricopeptide repeat motifs, it has been considered a non-canonical PPR protein because no one could demonstrate GUN1-RNA interaction in planta. However, through our computational analysis of PPR codes and subsequent biochemical studies, we were able to unravel its putative target RNA, namelypsbDBLRP. Therefore, our finding may lead to a reevaluation of GUN1 research in the context of RNA metabolism and a revision of our current understanding of GUN1.
Paternal starvation affects metabolic gene expression during zebrafish offspring development and life-long fitness
Authors: Jimenez-Gonzalez Ada , Ansaloni Federico , Nebendahl Constance , Alavioon Ghazal , Murray David , Robak Weronika , Sanges Remo , Müller Ferenc , Immler Simone 
Published: September 2023

AbstractDietary restriction is a putative key to a healthier and longer life, but these benefits may come at a trade-off with reproductive fitness and may affect the following generation(s). The potential inter- and transgenerational effects of starvation are particularly poorly understood in vertebrates when they originate from the paternal line. We utilised the externally fertilising zebrafish amenable to a split-egg clutch design to explore the male-specific effects of starvation on fertility and fitness of offspring independently of maternal contribution. Eighteen days of fasting resulted in reduced fertility in exposed males. While average offspring survival was not affected, we detected higher larval growth in offspring from starved males and increased malformation rates at 24 hours post fertilisation in the F2 embryos produced by the offspring of the starved males. The transcriptome analysis of embryos from starved and fed fathers revealed robust and reproducible induction of muscle composition genes and a contrasting repressive effect on lipid metabolism and lysosome genes. A large proportion of these genes showed enrichment in the yolk syncytial layer suggesting gene regulatory responses associated with metabolism of nutrients through paternal impact on extra embryonic tissues which are loaded with maternally deposited factors. We compared the embryo transcriptome to adult transcriptome datasets and demonstrated comparable repressive effects on metabolism-associated genes. These similarities suggest a physiologically relevant, directed and potentially adaptive response transmitted by the father, independently from the offspring’s nutritional state, which was defined by the mother.
The evolution of the duckweed ionome mirrors losses in structural complexity
Authors: Smith Kellie E , Zhou Min , Flis Paulina , Jones Dylan , Bishopp Anthony , Yant Levi 
Published: September 2023

ABSTRACTBackground and AimsThe duckweeds consist of 36 species exhibiting impressive phenotypic variation, including the progressive evolutionary loss of a fundamental plant organ, the root. Loss of roots and reduction of vascular tissues in recently derived taxa occur in concert with genome expansions of up to 14-fold. Given the paired loss of roots and reduction in structural complexity in derived taxa, we focus on the evolution of the ionome (whole-plant elemental contents) in the context of these fundamental body plan changes. We expect that progressive vestigiality and eventual loss of roots may have both adaptive and maladaptive consequences which are hitherto unknown.MethodsWe quantify the ionomes of 34 accessions in 21 species across all duckweed genera, spanning 70 million years in this rapid cycling plant (doubling times are as low as 24 hours). We relate both micro– and macroevolutionary ionome contrasts to body plan remodelling and show nimble microevolutionary shifts in elemental accumulation and exclusion in novel accessions.Key ResultsWe observe a robust directional trend in calcium and magnesium levels decreasing from the ancestral representativeSpirodelagenus towards the derived rootlessWolffia, with the latter also accumulating cadmium. We also identify abundant within-species variation and hyperaccumulators of specific elements, with this extensive variation at the fine– as opposed to broad-scale.ConclusionsThese data underscore the impact of root loss, and reveal the very fine scale of microevolutionary variation in hyperaccumulation and exclusion of a wide range of elements. Broadly, they may point to trade-offs not well recognized in ionomes.
In situ synchrotron X-ray total scattering measurements and analysis of colloidal CsPbX
3 nanocrystals during flow synthesis
Authors: Greenberg Matthew W. , Lin Cheng-Hung , Chodankar Shirish , Ghose Sanjit K. 
Published: September 2023

In situ X-ray scattering measurements of CsPbX
3 (X = Cl, Br, I) nanocrystal formation and halide exchange at NSLS-II beamlines were performed in an automated flow reactor. Total scattering measurements were performed at the 28-ID-2 (XPD) beamline and small-angle X-ray scattering at the 16-ID (LiX) beamline. Nanocrystal structural parameters of interest, including size, size distribution and atomic structure, were extracted from modeling the total scattering data. The results highlight the potential of these beamlines and the measurement protocols described in this study for studying dynamic processes of colloidal nanocrystal synthesis in solution with timescales on the order of seconds.