bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host microbiome-pathogen interactions in pediatric infections
Authors: Hurst Jillian H. , Heston Sarah M. , Kelly Matthew S. 
Published: July 2023

Purpose of review
In this review, we discuss recent research that has furthered our understanding of microbiome development during childhood, the role of the microbiome in infections during this life stage, and emerging opportunities for microbiome-based therapies for infection prevention or treatment in children.

Recent findings
The microbiome is highly dynamic during childhood and shaped by a variety of host and environmental factors. In turn, the microbiome influences risk and severity of a broad range of infections during childhood, with recent studies highlighting potential roles in respiratory, gastrointestinal, and systemic infections. The microbiome exerts this influence through both direct interactions with potential pathogens and indirectly through modulation of host immune responses. The elucidation of some of these mechanisms by recent studies and the development of effective microbiome-based therapies for adults with recurrent Clostridioides difficile infection highlight the enormous promise that targeting the microbiome has for reducing the burden of infectious diseases during childhood.

Summary
The microbiome has emerged as a key modifier of infection susceptibility and severity among children. Further research is needed to define the roles of microbes other than bacteria and to elucidate the mechanisms underlying microbiome-host and microbiome-pathogen interactions of importance to infectious diseases in children.
Long-term Stability Over 2 Years After Isolated Maxillary Orthognathic Surgery Combined With Mandibular Autorotation in Risk Patients for Condylar Resorption
Authors: Xiong Ni , Yang Hoon Joo , Kim Soung Min , Hwang Soon Jung 
Published: July 2023

Objective:
Counterclockwise rotation of mandible can cause condylar resorption and condylar displacement posteroinferiorly after maxillary orthognathic surgery with mandibular in patients with high-angle mandibular retrognathism. This study was aimed to evaluate long-term stability >2 years and postoperative changes of condylar displacement.

Materials and methods:
In 15 patients who underwent Le Fort I osteotomy with mandibular autorotation, postoperative stability was cephalometrically investigated until 2 years. Condylar changes were analyzed with transcranial temporomandibular joint projection. Correlation between condylar displacement and surgical movement was analyzed.

Results:
Significant clockwise relapse of mandible (P<0.01 for SNB reduction and backward movement of point B) was observed between 6 months and >2 years after surgery, even though the values were small (0.5±0.1 degrees and 1.14±0.13 mm, respectively). The condyle was displaced posteroinferiorly immediately after surgery; however, it achieved a stable position at postoperative 6 weeks. The amount of vertical condylar displacement was significantly correlated with surgical change in mandibular posterior border sagittal angle, palatal plane angle, facial height ratio, and point B in the horizontal dimension. Greater mandibular rotation prompted more vertical condylar displacement.

Conclusions:
Small mandibular relapse in long term should be considered after maxillary orthognathic surgery with mandibular autorotation, although it is regarded as a surgical maneuver to minimize mandibular instability in patients susceptible to postoperative condylar resorption.
Metabolic Interactive Nodular Network for Omics (MINNO): Refining and investigating metabolic networks based on empirical metabolomics data
Authors: Mandwal Ayush , Bishop Stephanie L. , Castellanos Mildred , Westlund Anika , Chaconas George , Lewis Ian , Davidsen Jörn 
Published: July 2023

ABSTRACTMetabolomics is a powerful tool for uncovering biochemical diversity in a wide range of organisms, and metabolic network modeling is commonly used to frame results in the context of a broader homeostatic system. However, network modeling of poorly characterized, non-model organisms remains challenging due to gene homology mismatches. To address this challenge, we developed Metabolic Interactive Nodular Network for Omics (MINNO), a web-based mapping tool that takes in empirical metabolomics data to refine metabolic networks for both model and unusual organisms. MINNO allows users to create and modify interactive metabolic pathway visualizations for thousands of organisms, in both individual and multi-species contexts. Herein, we demonstrate an important application of MINNO in elucidating the metabolic networks of understudied species, such as those of theBorreliagenus, which cause Lyme disease and relapsing fever. Using a hybrid genomics-metabolomics modeling approach, we constructed species-specific metabolic networks for threeBorreliaspecies. Using these empirically refined networks, we were able to metabolically differentiate these genetically similar species via their nucleotide and nicotinate metabolic pathways that cannot be predicted from genomic networks. These examples illustrate the use of metabolomics for the empirical refining of genetically constructed networks and show how MINNO can be used to study non-model organisms.GRAPHICAL ABSTRACTMINNO tool facilitates refining of metabolic networks, multi omics integration and investigation of cross-species interactions.
THE CEREBELLUM CONVERTS INPUT DATA INTO A HYPER LOW-RESOLUTION GRANULE CELL CODE WITH SPATIAL DIMENSIONS: A HYPOTHESIS
Authors: Gilbert Mike , Rasmussen Anders 
Published: July 2023

ABSTRACTWe present a theory of the inner layer of the cerebellar cortex, the granular layer, where the main excitatory input to the cerebellum is received. We ask how input signals are converted into an internal code and what form that has. While there is a computational element, and the ideas are quantified with a computer simulation, the approach is primarily evidence-led and aimed at experimenters rather than the computational community. Network models are often simplified to provide a noiseless medium for sophisticated computations. We propose, with evidence, the reverse: physiology is highly adapted to provide a noiseless medium for straightforward computations. We find that input data are converted to a hyper low-resolution internal code. Information is coded in the joint activity of large cell groups and therefore has minimum spatial dimensions – the dimensions of a code group. The conversion exploits statistical effects of random sampling. Code group dimensions are an effect of topography, cell morphologies and granular layer architecture. The activity of a code group is the smallest unit of information but not the smallest unit of code – the same information is coded in any random sample of signals. Code in this form is unexpectedly wasteful – there is a huge sacrifice of resolution – but may be a solution to fundamental problems involved in the biological representation of information.
The Effect of Gradual Ovarian Failure on Dynamic Muscle Function and the Role of High Intensity Interval Training on Mitigating Impairments
Authors: Hubbard Emma F. , Mashouri Parastoo , Pyle W Glen , Power Geoffrey A 
Published: July 2023

AbstractSkeletal muscle function is impaired in menopause and exercise may mitigate tshis decline. We used the VCD model of menopause to investigate the effects of gradual ovarian failure on skeletal muscle contractile function and whether high intensity interval training (HIIT) can mitigate impairments. Sexually mature female CD-1 mice were assigned to one of three groups: control (n=5), VCD-sedentary (n=5), or VCD-training (n=5). Following ovarian failure, the VCD-training group underwent 8 weeks of uphill HIIT. Mice were sacrificed 8 weeks after ovarian failure, representing late menopause. Single muscle fibres from the soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected, chemically permeabilized, and mechanically tested. Single muscle fibres were maximally activated (pCa 4.5) then isotonic load clamps were performed to calculate force-velocity-power curves. Absolute force and peak power were 31% and 32% lower in VCD-sedentary fibres compared to control fibres, respectively, in both SOL and EDL muscles. Despite reductions in absolute force and therefore lighter relative loads imposed during the isotonic contractions in VCD-sedentary fibres, there were no concomitant increases in contractile velocity. HIIT was partially effective at mitigating power loss (22% higher peak power in VCD-training compared to VCD-sedentary), but only in fast-type SOL fibres. These findings indicate that ovarian failure impairs dynamic contractile function – likely through a combination of lower force-generating capacity and slower shortening velocity – and that HIIT may be insufficient to completely counteract the deleterious effects of menopause at the cellular level.New & NoteworthyReductions in circulating ovarian hormones impair static muscle contractile performance, but less is known about dynamic properties like power.Typically, rodent models of menopause completely remove the ovaries and fail to mimic the prolonged and complex hormonal transition that includes a retention in ovarian androgen production.Using an ovary intact VCD model of ovarian failure, we found that single fibre power was impaired compared with controls in both SOL and EDL fibres.Our uphill high intensity interval training program was partially sufficient to reverse power loss, but only in fast-type SOL fibres.Impairments in muscle power following ovarian failure are likely driven by a combination of decreased muscle size and force-generating capacity.
Broadscale dampening of uncertainty adjustment in the aging brain
Authors: Kosciessa Julian Q. , Mayr Ulrich , Lindenberger Ulman , Garrett Douglas D. 
Published: July 2023

0.AbstractThe ability to prioritize among input features according to relevance enables adaptive behaviors across the human lifespan. However, relevance often remains ambiguous, and such uncertainty increases demands for dynamic control. While both cognitive stability and flexibility decline during healthy ageing, it is unknown whether aging alters how uncertainty impacts perception and decision-making, and if so, via which neural mechanisms. Here, we assess uncertainty adjustment across the adult lifespan (N = 100; cross-sectional) via behavioral modelling and a theoretically informed set of EEG-, fMRI-, and pupil-based signatures. On the group level, older adults show a broad dampening of uncertainty adjustment relative to younger adults. At the individual level, older individuals with more young-like neural responses also showed better maintained cognitive control. Our results highlight neural mechanisms whose maintenance plausibly enables flexible task-set, perception, and decision computations across the adult lifespan.
iPSC-Astrocyte morphology reflects patient clinical markers
Authors: Rowland Helen A. , Miller Georgina , Liu Qiang , Sharp Nicola , Ng Bryan , Wei Tina , Arunasalam Kanisa , Koychev Ivan , Hedegaard Anne , Ribe Elena M. , Chan Dennis , Chessell Tharani , Kocagoncu Ece , Lawson Jennifer , Malhotra Paresh , Ridha Basil H. , Rowe James B. , Thomas Alan J. , Zamboni Giovanna , Zetterberg Henrik , Cader M. Zameel , Wade-Martins Richard , Lovestone Simon , Nevado-Holgado Alejo , Kormilitzin Andrey , Buckley Noel J. 
Published: July 2023

AbstractHuman iPSCs provide powerful cellular models of Alzheimer’s disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer’s disease (AD) reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets. In this work iPSC-derived astrocytes were generated from a cohort of individuals with high versus low levels of the inflammatory marker YKL-40, in their cerebrospinal fluid (CSF). iPSC-derived astrocytes were treated with exogenous Aβ oligomers and high content imaging demonstrated a correlation between astrocytes that underwent the greatest morphology change from patients with low levels of CSF-YKL-40 and more protectiveAPOEgenotypes. This finding was subsequently verified using similarity learning as an unbiased approach. This study shows that iPSC-derived astrocytes from AD patients reflect key aspects of the pathophysiological phenotype of those same patients, thereby offering a novel means of modelling AD, stratifying AD patients and conducting therapeutic screens.Graphical Abstract
Nonlinear feedback modulation contributes to the optimization of flexible decision-making
Authors: Wu Xuanyu , Zhou Yang 
Published: July 2023

AbstractNeural activity in the primate brain correlates with both sensory evaluation and action selection aspects of decision-making. However, the intricate interaction between these distinct neural processes and their impact on decision behaviors remains unexplored. Here, we examined the interplay of these decision processes in posterior parietal cortex (PPC) when monkeys performed a flexible decision task. We found that the PPC activity related to monkeys’ abstract decisions about visual stimuli was nonlinearly modulated by monkeys’ following saccade choices directing outside each neuron’s response field. Recurrent neural network modeling indicated that the feedback connections, matching the learned stimuli-response associations during the task, mediated such feedback modulation. Further analysis on network dynamics revealed that selectivity-specific feedback connectivity intensified the attractor basins of population activity underlying saccade choices, thereby increasing the consistency of flexible decisions. These results highlight an iterative computation between different decision processes, mediated primarily by precise feedback connectivity, contributing to the optimization of flexible decision-making.
In vivofate of systemically administered encapsulin protein nanocages and implications for their use in targeted drug delivery
Authors: Rennie Claire , Sives Caitlin , Boyton India , Diaz Dennis , Gorrie Catherine A , Vittorio Orazio , Collins-Praino Lyndsey , Care Andrew 
Published: July 2023

AbstractEncapsulins, self-assembling protein nanocages derived from prokaryotes, are promising nanoparticle-based drug delivery systems (NDDS). However, thein vivobehavior and fate of encapsulins are poorly understood. In this pre-clinical study, we probe the interactions between the model encapsulin fromThermotoga maritima(TmEnc) and key biological barriers encountered by NDDS. Here, a purified TmEnc formulation that exhibited colloidal stability, storability, and blood compatibility was intravenously injected into BALB/c mice. TmEnc had an excellent nanosafety profile, with no abnormal weight loss or gross pathology observed, and only temporary alterations in toxicity biomarkers detected. Notably, TmEnc demonstrated immunogenic properties, inducing the generation of nanocage-specific IgM and IgG antibodies, but without any prolonged pro-inflammatory effects. An absence of antibody cross-reactivity also suggested immune-orthogonality among encapsulins systems. Moreover, TmEnc formed a serum-derived protein corona on its surface which changed dynamically and appeared to play a role in immune recognition. TmEnc’s biodistribution profile further revealed its sequestration from the blood circulation by the liver and then biodegraded within Kupffer cells, thus indicating clearance via the mononuclear phagocyte system. Collectively, these findings provide critical insights into how encapsulins behavein vivo,thereby informing their future design, modification, and application in targeted drug delivery.
Epigenetic Variation in Tree Evolution: a case study in black poplar (Populus nigra)
Authors: Sow Mamadou Dia , Rogier Odile , Lesur Isabelle , Daviaud Christian , Mardoc Emile , Sanou Edmond , Duvaux Ludovic , Civan Peter , Delaunay Alain , Descauses Marie-Claude Lesage- , Benoit Vanina , Le-Jan Isabelle , Buret Corinne , Besse Celine , Durufle Harold , Fichot Régis , Le-Provost Grégoire , Guichoux Erwan , Boury Christophe , Garnier Abel , Senhaji-Rachik Abdeljalil , Jorge Véronique , Ambroise Christophe , Tost Jorg , Plomion Christophe , Segura Vincent , Maury Stéphane , Salse Jérôme 
Published: July 2023

SUMMARYHow perennial organisms adapt to environments is a key question in biology. To address this question, we investigated ten natural black poplar (Populus nigra) populations from Western Europe, a keystone forest tree of riparian ecosystems. We assessed the role of (epi)genetic regulation in driving tree species evolution and adaptation over several millions of years (macro-evolution) up to a few generations (micro-evolution). At the macro-evolution scale, polar experienced differential structural (gene loss) and regulation (expression and methylation) reprogramming between sister genomic compartments inherited from polyploidization events. More interestingly, at the micro-evolution scale, both genetic and epigenetic variations differentiate populations from different geographic origins, targeting specifically genes involved in disease resistance, immune response, hormonal and stress response that can be considered as key functions of local adaptation of long lifespan species. Moreover, genes involved in cambium formation, an important functional trait for forest trees, as well as basal functions for cell survival are constitutively expressed though methylation control. These results highlight DNA methylation as a marker of population differentiation, evolutionary adaptation to diverse ecological environments and ultimately opening the need to take epigenetic marks into account in breeding strategies, especially for woody plants.
Urine lipoarabinomannan concentrations among HIV-uninfected adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam
Authors: Hoa Nguyen B. , Fajans Mark , Nguyen Van Hung , Vu Ngoc Bao , Nguyen Viet Nhung , Nguyen Thi Hoa , Thi Huong Lien Tran , Tran Minh Dung , Nguyen Kim Cuong , Thi Tuyet Trinh Ha , Huu Tri Nguyen , Ngoc Diep Bui , Viet Hai Nguyen , Khanh An Tran , Lillis Lorraine , Perez Marcos , Thomas Katherine K. , Peck Roger B. , Cantera Jason L. , Murphy Eileen , Halas Olivia R. , Storey Helen L. , Pinter Abraham , Ruhwald Morten , Drain Paul K. , Boyle David S. 
Published: July 2023

AbstractLipoarabinomannan (LAM) is a Mycobacterial cell wall glycolipid excreted in urine, and a target biomarker of rapid diagnostic tests (RDTs) for tuberculosis (TB) disease. Urine LAM (uLAM) testing by RDT has been approved for people living with HIV, but there is limited data regarding uLAM levels in HIV-negative adults with TB disease. We conducted a clinical study of adults presenting with TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent immunoassays and compared to a microbiological reference standard (MRS) of sputum, GeneXpert Ultra and TB culture. Additional microbiological testing was conducted for possible extrapulmonary TB, when clinically indicated. Among 745 participants enrolled, 335 (44.9 %) participants recruited from the pulmonary TB wards (PR-PTBW) and 6 (11.3%) participants recruited from the EPTB wards (PR-EPTBW) had confirmed TB disease. The MRS positive cohort measured median uLAM concentration for S4-20/A194-01 (S/A) were 14.5 pg/mL and 51.5 pg/mL, respectively. The FIND28/A194-01 (F/A) antibody pair overall and TB-positive cohort measured mean uLAM was 44.4 pg/mL and 78.1 pg/mL, respectively. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and specificity of 97% (95% CI 0.96, 0.99) against the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and specificity of 79% (95% CI 0.75, 0.84). The areas under the receiver operating curves were 0.748 for S/A and 0.629 for F/A. There was little difference between the S/A median uLAM concentration with pulmonary (55 pg/mL) and extrapulmonary (36 pg/mL) TB disease. With F/A the medians for pulmonary and extrapulmonary TB disease were 79% and 76.5% respectively. Among HIV-negative adults in Vietnam, concentrations of uLAM remained relatively low for people with TB disease, which may present challenges for developing a more sensitive rapid uLAM test.
Arabidopsis Transcription Factor WRKY45 Confers Cadmium Tolerance via ActivatingPCS1andPCS2Expression
Authors: Li Fangjian , Deng Yaru , Liu Yan , Mai Cuishan , Xu Yun , Wu Jiarui , Zheng Xinni , Liang Cuiyue , Wang Jinxiang 
Published: July 2023

AbstractCadmium (Cd) has long been recognized as toxic pollutant to crops worldwide. The biosynthesis of glutathione-dependent phytochelatin plays crucial roles in the detoxification of Cd in plants. However, its regulatory mechanism remains elusive. Here, we revealed that Arabidopsis transcription factor WRKY45 confers Cd tolerance via promoting the expression of PC synthesis-related genes PCS1 and PCS2, respectively. Firstly, we found that Cd stress induces the transcript levels of WRKY45 and its protein abundance. Accordingly, in contrast to wild type Col-0, the increased sensitivity to Cd is observed inwrky45mutant, while overexpressing WRKY45 plants are more tolerant to Cd. Secondly, quantitative real-time PCR revealed that the expression of AtPCS1 and AtPCS2 is stimulated in overexpressing WRKY45 plants, but decreased in wrky45 mutant. Thirdly, WRKY45 promotes the expression of PCS1 and PCS2, electrophoresis mobility shift assay analysis uncovered that WRKY45 directly bind to the W-box cis-element of PCS2 promoter. Lastly, the overexpression of WRKY45 in Col-0 leads to more accumulation of PCs in Arabidopsis, and the overexpression of PCS1 or PCS2 inwrky45mutant plants rescues the phenotypes induced by Cd stress. In conclusion, our results show that AtWRKY45 positively regulate Cd tolerance in Arabidopsis via activating PCS1 and PCS2 expression.Environmental implicationAccumulation of cadmium (Cd) in soils poses a threat to crop productivity and food safety. It has been revealed that phytochelatin (PC) plays an essential role in plants to alleviate Cd toxicity, yet the regulatory mechanisms governing its expression remain unclear. We have demonstrated that the Arabidopsis transcription factorWRKY45directly activates the expression ofPCS1andPCS2, which encode PC synthase, thereby increasing the content of PC and enhancing Arabidopsis tolerance to Cd stress. These findings offer insights into precise regulation strategies for crop Cd tolerance via modulation ofWRKY45homologue in crops.