bluuebunny/crossref_metadata_2025 huggingface dataset:
Perturbation of the mitochondrial import machinery by aggregation prone Tau affects organelle morphology and reduces neuronal complexity
Authors: Needs Hope I , Wilkinson Kevin A , Henley Jeremy M , Collinson Ian
Published: December 2022

Protein import into mitochondria is an intricate and highly conserved process essential for organellar biogenesis, and maintenance of its structure and function. Defects in the import apparatus impact the assembly of the respiratory chain and ATP synthase complexes required for oxidative phosphorylation, compromising the supply of ATP to the cytosol. The consequences of reduced bioenergetic function are particularly severe for cells with high energetic demands, such as neurons. However, relatively little is known about how defective import contributes to neurodegeneration, or how aggregation prone toxic proteins, characteristic of neurodegenerative disease, impact mitochondrial import efficiency. Here, we used HeLa cells to investigate how expressing Tau, or a disease-causing variant, affects mitochondrial import activity, morphology, and function. We found that a variant associated with frontotemporal dementia (TauP301L), but not the native version, colocalises with mitochondria, associating with TOM40–the protein-channel component of the outer membrane import complex. Interestingly, TauP301Lproduction had no discernible effect on overall mitochondrial import function, despite associating with TOM40 and altering mitochondrial morphology. This raised suspicions of a rescue mechanism manifested by the appearance of microtubule and actin containing tunnelling nanotubes (TNTs), used to recruit healthy mitochondria from neighbouring cells and/ or dispose of mitochondria containing aggregated Tau. Furthermore, in primary neuronal cultures TauP301Linduces morphological changes that resemble a neurodegeneration-like phenotype–also mirrored in cells where the import sites are blocked artificially. These results reveal an intriguing link between the production of aggregation prone protein variants, such as TauP301Land others, with the mitochondrial protein import machinery relevant to neurodegenerative disease.
Visual input dynamically changes responses to spatiotemporal tactile input patterns in S1 neurons
Authors: Kristensen Sofie Skårup , Jörntell Henrik
Published: December 2022

To understand how sensory events are represented in and perceived by the brain, one must understand how varying internal brain states affect neuronal decoding of sensory input. Recent studies indicate global state changes in the brain impact the representation of haptic events in neurons of the primary somatosensory cortex (S1). It could be argued that the manipulations used so far to alter the cortical circuitry behavior were artificial and not reflective of normal information processing in the neocortex. In the present study we therefore wanted to explore if natural visual stimulation also could impact the interpretation of given tactile input patterns. We recorded the unitary extracellular responses to a set of spatiotemporal tactile input patterns presented either alone or together with simultaneously multicolor flashing lights from a large number of neurons in parallel in the rat primary somatosensory cortex (S1). We found that the visual input, mildly but consistently altered the temporal spike outputs to tactile input patterns in S1 neurons. We argue that the visual input change the global cortical state to an extent that it affects the cortical representation of haptic events even within the S1 and that this is an indication that the cortical network in its information processing may be far more reliant on globally distributed network dynamics than traditionally thought.
Identifying content-invariant neural signatures of perceptual vividness
Authors: Barnett Benjy , Andersen Lau M. , Fleming Stephen M. , Dijkstra Nadine
Published: December 2022

Some conscious experiences are more vivid than others. Although perceptual vividness is a key component of human consciousness, how variation in this magnitude property is registered by the human brain is unknown. A striking feature of magnitudes in other psychological domains, such as number or reward, is the existence of neural magnitude codes that are independent from sensory contents. To test whether perceptual vividness similarly covaries with neural codes that are invariant to sensory content, we reanalysed existing MEG and fMRI data from two distinct studies, quantifying perceptual vividness via subjective ratings of awareness and visibility. Using representational similarity and decoding analyses, we find evidence for the existence of content-invariant neural codes for perceptual vividness distributed across visual, parietal, and frontal cortices. Our findings are consistent with a hypothesis that the subjective vividness of conscious experience is supported by neural signatures similar to magnitude codes in other cognitive domains.

Significance Statement

The vividness of conscious experience varies across different stimuli and contexts. Despite being a fundamental feature of conscious awareness, exactly how perceptual vividness is encoded in the human brain remains unclear. Neural codes underpinning magnitude in reward and numerosity domains have been shown to be unchanging as stimulus identity varies. Here, we test whether components of neural activity covarying with the magnitude of perceptual vividness are similarly independent of perceptual content in analyses of MEG and fMRI data. We find dynamic, content-invariant neural signatures of vividness in visual, parietal, and frontal cortices. Our findings introduce the surprising notion that neural signatures of conscious experience might follow similar coding principles to those found for magnitude properties of entirely different cognitive domains.
Toward a Cell Culture Model of Portal Axis Lipid Handling
Authors: Cook Joshua R. , Green Peter H.R. , Haeusler Rebecca A.
Published: December 2022

The health risks posed by excessive visceral white adipose tissue (WAT) may arise from exposure to deleterious intestinal factors in transit through the portal system. These may include an altered bile acid (BA) pool – particularly with respect to 12α-hydroxylated BA (12-HBA), which we have previously demonstrated are closely associated with insulin resistance. However, given the complexity of the enterohepatic milieu, we have worked to develop a co-culture system that allows for controlled study of the interactions between human induced pluripotent stem cell (hiPSC) derived adipocytes and primary human intestinal organoids (hIO). We present preliminary data on the characterization of both cellular compartments and their interactions, particularly in the context of BA treatment. We have recapitulated the basic functionality of each tissue type and have found reciprocal, potentially important changes in gene expression in each. However, we also have encountered numerous technical challenges in the development of this co-culture system and provide methodological observations to assist others seeking to work with a co-culture system of this type.
Down-regulation ofDrosophilaGlutactin, a cholinesterase-like adhesion molecule of the basement membrane, impairs development, compromises adult function and shortens lifespan
Authors: Alvarez-Ortiz Pedro , Guillemette Shawna , Humphrey Rachel , Ballif Bryan A. , Vigoreaux Jim O.
Published: December 2022

Basement membranes (BM) play fundamental roles in morphogenesis and tissue maintenance in multicellular organisms. Glutactin is a BM protein that belongs to the Cholinesterase-Like Adhesion Molecules (CLAMs) protein family. InDrosophilaembryos, Glutactin has been shown to outline internal organs and to play a role in synapse formation. Here, we report that Glutactin is broadly expressed in BM surrounding most vital tissues of the larva and the adult, and within the larval muscle sarcomere. Ubiquitous RNAi driven down-regulation of Glutactin expression (Tub>Glt-RNAi) resulted in pronounced impairments in larval and adult locomotor behavior, reduced oviposition, and shortened lifespan. Muscle-specific down-regulation of Glutactin resulted in reduced larval crawling speed indicating a secondary function for Glutactin independent of BM expression.Tub>Glt-RNAipupa showed abdominal scars, suggestive of defects in histoblast nest expansion and replacement of larval epidermal cells, and a high mortality rate at eclosion. Surviving adults showed a range of morphological and physiological defects including excess melanization and pigmentation, incomplete rotation and duplication of the genitalia, and abnormal heart morphology and contraction. Insofar excess melanization is symptomatic of internal tissue damage, we propose that Glutactin is essential for the mechanical stabilization of the BM and for its ability to withstand internal stresses.
Latent neural population dynamics underlying normal breathing, opioid induced respiratory depression, and gasping
Authors: Bush Nicholas E , Ramirez Jan-Marino
Published: December 2022

Breathing is vital and must be concurrently robust and flexible. This rhythmic behavior is generated and maintained within a rostro-caudally aligned set of medullary nuclei called the Ventral Respiratory Column (VRC). The rhythmic properties of individual VRC nuclei are well known, yet technical challenges have limited the interrogation of the entire VRC population simultaneously. Here, we characterize over 13,000 VRC units using high-density electrophysiology, opto-tagging, and histological reconstruction. Population dynamics analysis reveals interactions between inspiratory and expiratory dynamical states give rise to a low-dimensional, elliptical neural manifold. The structure of this manifold is robust and maintained even during opioid-induced respiratory depression (OIRD). However, during severe hypoxia-induced gasping, the low-dimensional dynamics of the VRC reconfigure from rotational to all-or-none, ballistic efforts.
Quantifying negative selection in human 3’ UTRs uncovers constrained targets of RNA-binding proteins
Authors: Findlay Scott D. , Romo Lindsay , Burge Christopher B.
Published: December 2022

Many non-coding variants associated with phenotypes occur in 3’ untranslated regions (3’ UTRs) and may affect interactions with RNA-binding proteins (RBPs) to regulate post-transcriptional gene expression. However, identifying functional 3’ UTR variants has proven difficult. We used allele frequencies from the Genome Aggregation Database (gnomAD) to identify classes of 3’ UTR variants under strong negative selection in humans. We developed intergenic mutability-adjusted proportion singleton (iMAPS), a generalized measure related to MAPS, to quantify negative selection in non-coding regions. This approach, in conjunction within vitroandin vivobinding data, identifies precise RBP binding sites, miRNA target sites, and polyadenylation signals (PASs) under strong selection. For each class of sites, we identified thousands of gnomAD variants under selection comparable to missense coding variants, and found that sites in core 3’ UTR regions upstream of the most-used PAS are under strongest selection. Together, this work improves our understanding of selection on human genes and validates approaches for interpreting genetic variants in human 3’ UTRs.
Hyperglycemia increases the severity ofStaphylococcus aureusosteomyelitis and influences bacterial genes required for survival in bone
Authors: Butrico Casey E. , Klopfenstein Nathan B. , Green Erin R. , Johnson Joshua R. , Peck Sun H. , Ibberson Carolyn B. , Serezani C. Henrique , Cassat James E.
Published: December 2022

Hyperglycemia, or elevated blood glucose, renders individuals more prone to developing severeStaphylococcus aureusinfections.S. aureusis the most common etiological agent of musculoskeletal infection, which is a common manifestation of disease in hyperglycemic patients. However, the mechanisms by whichS. aureuscauses severe musculoskeletal infection during hyperglycemia are incompletely characterized. To examine the influence of hyperglycemia onS. aureusvirulence during invasive infection, we used a murine model of osteomyelitis and induced hyperglycemia with streptozotocin. We discovered that hyperglycemic mice exhibited increased bacterial burdens in bone and enhanced dissemination compared to control mice. Furthermore, infected hyperglycemic mice sustained increased bone destruction relative to euglycemic controls, suggesting that hyperglycemia exacerbates infection-associated bone loss. To identify genes contributing toS. aureuspathogenesis during osteomyelitis in hyperglycemic animals relative to euglycemic controls, we used transposon sequencing (TnSeq). We identified 71 genes uniquely essential forS. aureussurvival in osteomyelitis in hyperglycemic mice and another 61 mutants with compromised fitness. Among the genes essential forS. aureussurvival in hyperglycemic mice was superoxide dismutase A (sodA), one of twoS. aureussuperoxide dismutases involved in detoxifying reactive oxygen species (ROS). We determined that asodAmutant exhibits attenuated growthin vitroin high glucose andin vivoduring osteomyelitis in hyperglycemic mice. SodA therefore serves an important role during growth in high glucose and promotesS. aureussurvival in bone. Collectively, these studies demonstrate that hyperglycemia increases the severity of osteomyelitis and identify genes contributing toS. aureussurvival during hyperglycemic infection.
Examining the Responsiveness of the National Health Insurance Fund (NHIF) to People Living with Hypertension and Diabetes in Kenya: A qualitative study
Authors: Oyando Robinson , Were Vincent , Willis Ruth , Koros Hillary , Kamano Jemima , Naanyu Violet , Etyang Anthony , Mugo Richard , Murphy Adrianna , Nolte Ellen , Perel Pablo , Barasa Edwine
Published: December 2022

Objectives: To assess the responsiveness of the National Health Insurance Fund (NHIF) Supa Cover benefit package to the needs of individuals with diabetes and hypertension in Kenya. Design, setting and participants: We carried out a qualitative study and collected data using key informant interviews (n = 39) and focus group discussions (n = 4) in two purposively selected counties in Western Kenya. Study participants were drawn from NHIF officials, county government officials, health facility managers, healthcare workers and individuals with NCDs who were enrolled in NHIF. We analysed data using thematic analysis. Results: Study participants reported that the NHIF Supa Cover benefit package expanded access to services for people living with NCDs. However, the NHIF members and healthcare workers had inadequate awareness of the NHIF service entitlements. The NHIF benefit package inadequately covered the range of services needed by people living with NCDs and the benefits package did not prioritise preventive and promotive services. Sometimes NCD patients were discriminated against by healthcare providers who preferred cash-paying patients, and some NHIF-empanelled health facilities had inadequate structural inputs essential for quality of care. Study participants felt that the NHIF premium for the general scheme was unaffordable, and NHIF members faced additional out-of-pocket costs because of additional payments for services not available or covered. Conclusion: Whereas NHIF has reduced financial barriers for NCD patients, to enhance its responsiveness to patient needs, NHIF should implement mechanisms to increase benefit package awareness among members and providers. In addition, preventive and promotive services should be included in NHIF's benefits package and mechanisms to monitor and hold contracted providers accountable should be strengthened.
Modeling and Simulation of CAR T cell Therapy in Chronic Lymphocytic Leukemia Patients
Authors: Nukala Ujwani , Messan Marisabel Rodriguez , Yogurtcu Osman N. , Sauna Zuben , Yang Hong
Published: December 2022

Advances in genetic engineering have made it possible to reprogram an individual’s immune cells to express receptors that recognize markers on tumor cell surfaces. The process of re-engineering T cell lymphocytes to express Chimeric Antigen Receptors (CARs) and reinfusing the CAR-modified T cells into patients to treat various cancers is being explored in clinical trials. While the majority of patients with some cancers (e.g., B cell acute lymphocytic leukemia) respond to CAR-T cell therapy, this success is not evidenced in all cancers. For example, only 26% of Chronic Lymphocytic Leukemia (CLL) patients respond to CAR T cell therapy. Understanding of the factors associated with an individual patient’s response is important for patient selection and could help develop more effective CAR T cell therapies. Here we present a mechanistic mathematical model to identify factors associated with responses to CAR T cell therapeutic interventions. The proposed model is a system of coupled ordinary differential equations designed based on known immunological principles and prevailing hypotheses on the mechanism of CAR T cell kinetics, Interleukin 6 (IL-6) secretion, and tumor killing in CAR T cell therapy. The model reportsin silicodisease outcomes using B cell concentration as a surrogate biomarker. Our results are consistent with thein vitroexperimental observations that CAR T cell fitness in terms of its tumor cell killing capacity and proliferation plays an important role in the patient response. We demonstrate the utility of mathematical modelling in understanding the factors that play an important role in patient response to CAR T cell therapy.
Mapping young people’s journeys through mental health services: a prospective longitudinal qualitative study protocol
Authors: Pilbeam Caitlin , Walsh Erin , Barnes Katelyn , Scholz Brett , Olsen Anna , Stone Louise
Published: December 2022

Mental ill health is a major health risk for young people. There is unmet need for mental health assessment and treatment across Australia despite significant investment in government-funded plans to cover mental health and youth-oriented services. Understandings of mental health care for young people are impeded by a lack of longitudinal research. Without this research, it is difficult to understand how services do or do not support the recovery of young people over time.

This project will analyse the healthcare journeys of young people aged 16-25 years experiencing their first significant episode of mental ill health, over 12 months in the Australian Capital Territory. The study team will recruit up to 25 diverse young people and their general practitioners (GPs), and conduct four qualitative semi-structured interviews over 12 months with each participant. GP interviews will explore their role in the mental health care and care coordination for the young person. Interviews with young people will explore experiences and perceptions of navigating the health system, and the supports and resources they engaged with during the 12-month period. In between interviews, young people will be asked to keep a record of their mental health care experiences, through their choice of media. Participant-produced materials will also form the basis for interviews, providing stimuli to discuss the lived experience of care.

Through analysing the narratives of both young people and their GPs, the study will establish how young people understand value in mental health care delivery. The study will use longitudinal qualitative mapping of healthcare journeys to identify key barriers and enablers to establishing effective, person-centred health care for young people with mental ill health.
Chemical factors induce aggregative multicellularity in a close unicellular relative of animals
Authors: Ros-Rocher Núria , Kidner Ria Q. , Gerdt Catherine , Davidson W. Sean , Ruiz-Trillo Iñaki , Gerdt Joseph P.
Published: December 2022

Regulated cellular aggregation is an essential process for development and healing in many animal tissues. In some animals and a few distantly related unicellular species, cellular aggregation is regulated by diffusible chemical cues. However, it is unclear whether regulated cellular aggregation was part of the life cycles of the first multicellular animals and/or their unicellular ancestors. To fill this gap, we investigated the triggers of cellular aggregation in one of animals’ closest unicellular living relatives – the filastereanCapsaspora owczarzaki. We discovered thatCapsasporaaggregation is induced by chemical cues, as observed in some of the earliest branching animals and other unicellular species. Specifically, we found that calcium ions and lipids present in lipoproteins function together to induce aggregation of viableCapsasporacells. We also found that this multicellular stage is reversible, as depletion of the cues triggers disaggregation, which can be overcome upon re-induction. Our finding demonstrates that chemically regulated aggregation is important across diverse members of the holozoan clade. Therefore, this phenotype was plausibly integral to the life cycles of the unicellular ancestors of animals.
PI 3-kinase isoform p110α controls smooth muscle cell functionality and protects against aortic aneurysm formation
Authors: Vantler Marius , Schorscher Maximilian , Berghausen Eva Maria , Moore Joseph B. , Wong Dickson , Zhaolong Li , Wißmüller Max , Gnatzy-Feik Leoni , Zierden Mario , Mehrkens Dennis , Adam Matti , Zhao Xinlei , Odenthal Margarete , Sengle Gerhard , Boor Peter , Maegdefessel Lars , Baldus Stephan , Rosenkranz Stephan
Published: December 2022

Background

Catalytic class IA PI 3-kinase isoform p110α is a crucial regulator of cellular proliferation and survival in numerous cell types. While p110α is critically involved in pathogenic vascular remodeling, its physiological role for vascular integrity under stress conditions has not been studied. We report a protective function of smooth muscle p110α against abdominal aortic aneurysm (AAA) formation.

Methods & Results

In mice lacking p110α in smooth muscle cells (sm-p110α-/-), perfusion of the infrarenal aorta with porcine pancreatic elastase (PPE) yielded substantially enhanced AAA formation compared to wild type controls. This disease phenotype is partly attributable to a subtle preexisting vascular phenotype under basal conditions, as sm-p110α-/-mice displayed a smaller media area, deranged aortic wall structure (detached smooth muscle cells, increased apoptotic cell death), and a diminished functional responsiveness of aortic rings to vasodilators. Furthermore, p110α is also implicated in regenerative processes during AAA development: Whereas wild type mice showed increased media hypertrophy, neointima formation and proliferation upon PPE intervention, these vascular remodeling processes were diminished in sm-p110α-/-mice. Concomitantly, increased numbers of elastic fiber breaks and ECM degradation were detected in sm-p110α-/-aorta. Mechanistically, we found that lack of p110α expression impaired smooth muscle cell proliferation, expression of contractile marker genes and production of elastin fibers. This phenotype largely depended on reduced phosphorylation and inactivation of FOXO1, as specific FOXO1 inhibition fully rescued proliferation of p110α-/-smooth muscle cells, and knockdown of FOXO1 increased expression of calponin and elastin.

Conclusions

Smooth muscle p110α protects against AAA disease by maintaining aortic wall homoeostasis and promoting SMC proliferation to compensate for cell loss during AAA development. Our findings have potential implications for current approaches aimed at p110α inhibition for cancer therapy and suggest new pharmacological strategies to activate p110α signaling in AAA disease.
Filter-based models of suppression in retinal ganglion cells: comparison and generalization across species and stimuli
Authors: Shahidi Neda , Rozenblit Fernando , Khani Mohammad H. , Schreyer Helene M. , Mietsch Matthias , Protti Dario A. , Gollisch Tim
Published: December 2022

The dichotomy of excitation and suppression is one of the canonical mechanisms explaining the complexity of neural activity. Computational models of the interplay of excitation and suppression in single neurons aim at investigating how this interaction affects a neuron’s spiking responses and shapes the encoding of sensory stimuli. Here, we compare the performance of three filter-based stimulus-encoding models for predicting retinal ganglion cell responses recorded from axolotl, mouse, and marmoset retina to different types of temporally varying visual stimuli. Suppression in these models is implemented via subtractive or divisive interactions of stimulus filters or by a response-driven feedback module. For the majority of ganglion cells, the subtractive and divisive models perform similarly and outperform the feedback model as well as a linear-nonlinear (LN) model with no suppression. Comparison between the subtractive and the divisive model depended on cell type, species, and stimulus components, with the divisive model generalizing best across temporal stimulus frequencies and visual contrast and the subtractive model capturing in particular responses for slow temporal stimulus dynamics and for slow axolotl cells. Overall, we conclude that the divisive and subtractive models are well suited for capturing interactions of excitation and suppression in ganglion cells and perform best for different temporal regimes of these interactions.
Liver transcriptomic and methylomic analyses identify transcriptional MAPK regulation in facultative hibernation of Syrian hamster
Authors: Oosterhof Marloes M. , Coussement Louis , Guryev Victor , Reitsema Vera A. , Bruintjes Jojanneke J. , Goris Maaike , Bouma Hjalmar R. , de Meyer Tim , Rots Marianne G. , Henning Robert H.
Published: December 2022

Hibernation consist of alternating torpor/arousal phases, during which animals cope with repetitive hypothermia and ischemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole genome bisulfite sequencing in liver of hibernating Syrian hamster(Mesocricetus auratus). Gene Ontology analysis was performed on 844 differentially expressed genes (DEGs) and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. We show a so far unreported suppression of MAPK and PP1 pathways. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (DUSPs and SPRYs) and reduced levels of MAPK induced transcription factors. Promoter methylation was found to modulate the expression of genes targeted by these transcription factors. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischemia-reperfusion.
Optimization of host cell-compatible, antimicrobial peptides effective against biofilms and clinical isolates of drug-resistant bacteria
Authors: Ghimire Jenisha , Hart Robert J. , Soldano Anabel , Chen Charles H. , Guha Shantanu , Hoffmann Joseph P. , Hall Kalen M. , Sun Leisheng , Nelson Benjamin J. , Lu Timothy K. , Kolls Jay K. , Rivera Mario , Morici Lisa A. , Wimley William C.
Published: December 2022

Here, we describe the continued synthetic molecular evolution of a lineage of host-compatible antimicrobial peptides (AMP) intended for the treatment of wounds infected with drug-resistant, biofilm-forming bacteria. The peptides tested are variants of an evolved AMP called D-CONGA, which has excellent antimicrobial activitiesin vitroandin vivo. In this newest generation of rational D-CONGA variants, we tested multiple sequence-structure-function hypotheses that had not been tested in previous generations. Many of the peptide variants have lower antibacterial activity against Gram-positive or Gram-negative pathogens, especially variants that have altered hydrophobicity, secondary structure potential, or spatial distribution of charged and hydrophobic residues. Thus, D-CONGA is generally well tuned for antimicrobial activity. However, we identified a variant, D-CONGA-Q7, with a polar glutamine inserted into the middle of the sequence, that has higher activity against both planktonic and biofilm-forming bacteria as well as lower cytotoxicity against human fibroblasts. Against clinical isolates ofK. pneumoniae, innate resistance to D-CONGA was surprisingly common despite a lack of inducible resistance inP. aeruginosareported previously. Yet, these same isolates were susceptible to D-CONGA-Q7. D-CONGA-Q7 is much less vulnerable to AMP resistance in Gram-negative bacteria than its predecessor. Consistent with the spirit of synthetic molecular evolution, D-CONGA-Q7 achieved a critical gain-of-function and has a significantly better activity profile.
Mcr-dependent methanogenesis inArchaeoglobaceaeenriched from a terrestrial hot spring
Authors: Buessecker Steffen , Chadwick Grayson L. , Quan Melanie E. , Hedlund Brian P. , Dodsworth Jeremy A. , Dekas Anne E.
Published: December 2022

The preeminent source of biological methane on Earth is methyl coenzyme M reductase (Mcr)-dependent archaeal methanogenesis. A growing body of evidence suggests a diversity of archaea possess Mcr, however, experimental validation of hypothesized methane metabolisms has been missing. Here, we provide evidence of a functional Mcr-based methanogenesis pathway in a novel member of the familyArchaeoglobaceae, designatedMethanoproducendum nevadense, which we enriched from a terrestrial hot spring on the polysaccharide xyloglucan. Our incubation assays demonstrate methane production that is highly sensitive to the Mcr-inhibitor bromoethanesulfonate, stimulated by xyloglucan and xyloglucan-derived sugars, concomitant with the consumption of molecular hydrogen, and causing a deuterium fractionation in methane characteristic of hydrogenotrophic and methylotrophic methanogens. Combined with the recovery and analysis of a high-qualityM. nevadensemetagenome-assembled genome encoding a divergent Mcr and diverse potential electron and carbon transfer pathways, our observations suggest methanogenesis inM. nevadenseoccurs via Mcr and is fueled by the consumption of cross-fed byproducts of xyloglucan fermentation mediated by other community members. Phylogenetic analysis shows close affiliation of theM. nevadenseMcr with those from Korarchaeota, Nezhaarchaeota, Verstraetearchaeota, and otherArchaeoglobalesthat are divergent from well-characterized Mcrs. We propose these archaea likely also use functional Mcr complexes to generate methane on the basis of our experimental validation inM. nevadense. Although our stable isotope approach reveals that microbial methanogenesis contributes only a small proportion of the overall methane abundance in the native habitat, divergent Mcr-encoding archaea may be underestimated sources of biological methane in terrestrial and marine hydrothermal environments.
Kinetics and targeting of Vipp1 aggregation in cyanobacteria
Authors: Gates Colin , Hill Nicholas C. , Dahlgren Kelsey , Cameron Jeffrey C.
Published: December 2022

The kinetics of regulation of vesicle-inducing protein in plastids (Vipp1), an essential protein in all oxygenic phototrophs, are not completely understood. Vipp1 is responsible for both membrane maintenance and damage repair processes, aggregating at sites of damage (proton leakage) or physical strain (responding to presence of anionic lipids). Herein we spatiotemporally resolve exchange between inactive cytoplasmic Vipp1 and these two functionalities. We demonstrate that Vipp1 can be aggregated to a specific site in the thylakoid membrane by laser damage, but this behavior appears to be mediated by a rapidly resolved secondary process, as cytoplasmic Vipp1 is rendered unresponsive to nearby damage on a time scale three orders of magnitude faster than the aggregation process itself.

One Sentence Summary

Vipp1 aggregation to points on the thylakoid is induced in response to specific damage and repair kinetics are observed.
Neural mechanisms of parasite-induced summiting behavior in “zombie”Drosophila
Authors: Elya Carolyn , Lavrentovich Danylo , Lee Emily , Pasadyn Cassandra , Duval Jasper , Basak Maya , Saykina Valerie , de Bivort Benjamin
Published: December 2022

For at least two centuries, scientists have been enthralled by the “zombie” behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the recently establishedEntomophthora muscae-Drosophila melanogaster“zombie fly” system to reveal the molecular and cellular underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a new, high-throughput behavior assay to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), who are solely responsible for juvenile hormone (JH) synthesis and release. Summiting is a fleeting phenomenon, posing a challenge for physiological and biochemical experiments requiring tissue from summiting flies. We addressed this with a machine learning classifier to identify summiting animals in real time. PI-CA neurons and CA appear to be intact in summiting animals, despiteE. muscaecells invading the host brain, particularly in the superior medial protocerebrum (SMP), the neuropil that contains DN1p axons and PI-CA dendrites. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the fly’s hemolymph, activating the neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host.
The complete sequence of a human Y chromosome
Authors: Rhie Arang , Nurk Sergey , Cechova Monika , Hoyt Savannah J. , Taylor Dylan J. , Altemose Nicolas , Hook Paul W. , Koren Sergey , Rautiainen Mikko , Alexandrov Ivan A. , Allen Jamie , Asri Mobin , Bzikadze Andrey V. , Chen Nae-Chyun , Chin Chen-Shan , Diekhans Mark , Flicek Paul , Formenti Giulio , Fungtammasan Arkarachai , Garcia Giron Carlos , Garrison Erik , Gershman Ariel , Gerton Jennifer L. , Grady Patrick G.S. , Guarracino Andrea , Haggerty Leanne , Halabian Reza , Hansen Nancy F. , Harris Robert , Hartley Gabrielle A. , Harvey William T. , Haukness Marina , Heinz Jakob , Hourlier Thibaut , Hubley Robert M. , Hunt Sarah E. , Hwang Stephen , Jain Miten , Kesharwani Rupesh K. , Lewis Alexandra P. , Li Heng , Logsdon Glennis A. , Lucas Julian K. , Makalowski Wojciech , Markovic Christopher , Martin Fergal J. , Mc Cartney Ann M. , McCoy Rajiv C. , McDaniel Jennifer , McNulty Brandy M. , Medvedev Paul , Mikheenko Alla , Munson Katherine M. , Murphy Terence D. , Olsen Hugh E. , Olson Nathan D. , Paulin Luis F. , Porubsky David , Potapova Tamara , Ryabov Fedor , Salzberg Steven L. , Sauria Michael E.G. , Sedlazeck Fritz J. , Shafin Kishwar , Shepelev Valery A. , Shumate Alaina , Storer Jessica M. , Surapaneni Likhitha , Taravella Oill Angela M. , Thibaud-Nissen Françoise , Timp Winston , Tomaszkiewicz Marta , Vollger Mitchell R. , Walenz Brian P. , Watwood Allison C. , Weissensteiner Matthias H. , Wenger Aaron M. , Wilson Melissa A. , Zarate Samantha , Zhu Yiming , Zook Justin M. , Eichler Evan E. , O’Neill Rachel J. , Schatz Michael C. , Miga Karen H. , Makova Kateryna D. , Phillippy Adam M.
Published: December 2022

The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure including long palindromes, tandem repeats, and segmental duplications1–3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4, 5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029 base pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, revealing the complete ampliconic structures ofTSPY,DAZ, andRBMYgene families; 41 additional protein-coding genes, mostly from theTSPYfamily; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a prior assembly of the CHM13 genome4and mapped available population variation, clinical variants, and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.
Orthogonal neural encoding of targets and distractors supports multivariate cognitive control
Authors: Ritz Harrison , Shenhav Amitai
Published: December 2022

The complex challenges of our mental life require us to coordinate multiple forms of neural information processing. Recent behavioral studies have found that people can coordinate multiple forms of attention, but the underlying neural control process remains obscure. We hypothesized that the brain implements multivariate control by independently monitoring feature-specific difficulty and independently prioritizing feature-specific processing. During fMRI, participants performed a parametric conflict task that separately tags target and distractor processing. Consistent with feature-specific monitoring, univariate analyses revealed spatially segregated encoding of target and distractor difficulty in dorsal anterior cingulate cortex. Consistent with feature-specific attentional priority, a novel multivariate analysis (Encoding Geometry Analysis) revealed overlapping, but orthogonal, representations of target and distractor coherence in intraparietal sulcus. Coherence representations were mediated by control demands and aligned with both performance and frontoparietal activity, consistent with top-down attention. Together, these findings provide evidence for the neural geometry necessary to coordinate multivariate cognitive control.
A phase retrieval algorithm for triply periodic minimal surface like structures
Authors: Oka Toshihiko
Published: December 2022

A method to solve the crystallographic phase problem of materials with triply periodic minimal surface like structures, such as lyotropic liquid crystal bicontinuous cubic phases, is reported. In triply periodic minimal surface like structures, the difference between the maximum and minimum electron densities tends to be the smallest for the true phase combination among the possible combinations [Oka (2022). Acta Cryst. A78, 430–436]. Using this feature, a new iterative phase retrieval algorithm for structure determination was developed. The algorithm modifies electron densities outside the upper and lower thresholds in the iterative Fourier transformation process with fixed amplitudes for the structure factors, and efficiently searches for the structure with the smallest difference between the maximum and minimum electron densities. The proper structure was determined by this algorithm for all tested data for lyotropic liquid crystal bicontinuous cubic phases and mesoporous silicas. Although some cases required constraints such as the volume fraction for structure determination, more than half could be determined without any constraints, including space groups.
Climate change, extreme events and mental health in the Pacific region
Authors: Leal Filho Walter , Krishnapillai Murukesan , Minhas Aprajita , Ali Sannia , Nagle Alverio Gabriela , Hendy Ahmed Medhat Sayed , Naidu Roselyn , Prasad Ravinesh R. , Bhullar Navjot , Sharifi Ayyoob , Nagy Gustavo J. , Kovaleva Marina
Published: December 2022

Purpose

This paper aims to address a gap in investigating specific impacts of climate change on mental health in the Pacific region, a region prone to extreme events. This paper reports on a study on the connections between climate change, public health, extreme weather and climate events (EWEs), livelihoods and mental health, focusing on the Pacific region Islands countries.

Design/methodology/approach

This paper deploys two main methods. The first is a bibliometric analysis to understand the state of the literature. For example, the input data for term co-occurrence analysis using VOSviewer is bibliometric data of publications downloaded from Scopus. The second method describes case studies, which outline some of the EWEs the region has faced, which have also impacted mental health.

Findings

The results suggest that the increased frequency of EWEs in the region contributes to a greater incidence of mental health problems. These, in turn, are associated with a relatively low level of resilience and greater vulnerability. The findings illustrate the need for improvements in the public health systems of Pacific nations so that they are in a better position to cope with the pressures posed by a changing environment.

Originality/value

This paper contributes to the current literature by identifying the links between climate change, extreme events, environmental health and mental health consequences in the Pacific Region. It calls for greater awareness of the subject matter of mental health among public health professionals so that they may be better able to recognise the symptoms and relate them to their climate-related causes and co-determinant factors.
Climate risk, climate risk distance and foreign direct investment
Authors: Xing Zhaopeng , Wang Yawen
Published: December 2022

Purpose

Climate risk greatly increases the risk exposure of global investments. Both the climate risks of home countries and host countries may affect international investment behaviors. The purpose of this paper is to explore the impact of climate risk and climate risk distance on foreign direct investment (FDI) inflows and outflows. Targeted proposals are provided to promote international economic and trade cooperation and the authors provide suggestions for the FDI strategies of multinational enterprises.

Design/methodology/approach

The authors define “climate risk distance” as the difference in climate risks between two countries. This paper uses both a theoretical model and a generalized least squares test to investigate the impact of climate risk distance on FDI from the perspectives of FDI inflows and outflows. In addition, the authors subdivide the samples according to the sign of climate risk distance and rank the FDI share from home country to host country into four groups according to the host country’s climate risk index. Finally, the authors undertake empirical tests with outward foreign direct investment (OFDI) data to support the empirical results.

Findings

Investors from countries with low climate risks have the upper hand due to their competitive advantages, like their skills, trademarks and patent rights, which they can transfer abroad to offset the disadvantage of being non-native. This is generally defined as ownership advantage. The impact of climate risk distance on FDI depends on the sign of climate risk distance. Specifically, host countries with higher climate risks compared with the climate risk levels of home countries may experience insignificant reductions in FDI inflows. For investors from home countries with higher climate risks, they are less likely to invest in host countries with lower climate risks. The results for samples from emerging market economies are shown to be more significant.

Originality/value

This study advances the O (ownership advantage) part of the ownership, location and internationalization (OLI) paradigm by incorporating the climate risk distance between the home country and the host country into the influencing factors of FDI. Both the O part and the L (location advantage, the advantage that host countries offers to make internationalization worthwhile to undertake FDI) part of the OLI paradigm concerning climate risks are validated with FDI and OFDI data.
Implementing structural equation modelling and multiple mediator models for management information systems
Authors: Osman Esam , Hardaker Glenn , Glenn Liyana Eliza
Published: December 2022

Purpose

Overall quantitative research aims to observe certain fundamental principles of logic and scientific frame of reasoning. There continues to be challenges on how quantitative research is conducted in the field of information systems.

Design/methodology/approach

Structured equation modelling (SEM) research identifies concerns about the standard of scientific enquiry method, the issue of the misconception of sustaining the consequent and the issue of collective validity. Therefore, rigor and robustness in instrument validity, constructs validity and path analysis validity maybe better achieved by attending to these three concerns. Measuring a multiple mediator construct in a hypothetical model continues to be a challenge for researchers in information systems research and related fields.

Findings

This paper aims to provide a thoughtful assessment of the contemporary issues of structural equation modelling methodology (SEMM), by providing rigid and robust SEMM that has several stages in specifying valid multiple mediators construct and the process to measuring in a path analysis model. This paper attempts to develop each stage of the methodology using relevant research to construct a methodology specified to test effects in multiple mediators in SEM using AMOS software. The methodology developed contains the two main phases; first is prior to data collection phase and the second phase is after the data collection, the use of this methodology design, for implementation, intended to support high methodological standards and subsequent quality in MIS research findings.

Originality/value

The research paper provides SEMM that has several stages in specifying valid multiple mediators construct and the process to measuring in a path analysis model.
Intellectual capital disclosure and its determinants in healthcare organisations – Evidence from Italy
Authors: Nicolò Giuseppe , Ferullo Diana , Aversano Natalia , Ardito Nadia
Published: December 2022

Purpose

The present study aims to extend the knowledge of intellectual capital disclosure (ICD) disclosure practices in the Italian Healthcare Organisations (HCOs) context. The ultimate goal of the study is to provide fresh insight into the possible explanatory factors that may drive the extent of ICD provided by Italian HCOs via the web.

Design/methodology/approach

The present study applies a manual content analysis on the websites of a sample of 158 HCOs to determine the level of voluntary ICD. A multivariate regression model is estimated to test the association between different variables – size, gender diversity in top governance positions, financial performance and indebtedness – and the level of ICD provided by sampled HCOs through their official websites.

Findings

Content analysis results reveal that – in the absence of mandatory requirements – Italian HCOs tend to use websites to disclose information about IC. Particular attention is devoted to Structural and Relational Capital. The statistical analysis pinpoints that size and indebtedness negatively influence the level of ICD. In contrast, the presence of a female General Manager (GM) positively drives ICD. Also, it is observed that Research and University HCOs and those located in the Italian Northern Regions are particularly prone to discharge accountability on IC through websites.

Originality/value

To the best of the authors’ knowledge, this is the first study that examines voluntary ICD practices through websites in the Italian HCOs' context. Also, since prior studies on IC in the healthcare context are mainly descriptive or normative, this is the first study examining the potential determinants of ICD provided by HCOs in terms of size, gender diversity in top governance positions, financial performance and indebtedness.