bluuebunny/crossref_metadata_2025 huggingface dataset:
Glyphosate resistance evolution to lethal and sublethal doses in chemostat populations of model organismChlamydomonas reinhardtii
Authors: Hansson Erika M. , Childs Dylan Z. , Beckerman Andrew P.
Published: February 2024

Herbicide resistant weeds are an increasing economic and ecological problem world-wide. Evolutionary theory and insight from experiments testing this theory are now a central part of solving resistance problems. More specifically, experimental evolution, where populations are allowed to evolve under specific conditions, can offer substantial insights into the trade-offs that govern the pace at which resistance arises. Here we leverage the green algaChlamydomonas reinhardtiifacing glyphosate as a model plant system to evaluate such theory, monitoring the level of evolved resistance and associated fitness costs throughout the course of adaptation. On a gradient of lethal and sub-lethal doses of glyphosate, we found evidence for evolved resistance from standing genetic variation but limited evidence for classic growth rate trade-offs that are expected to affect the pace of resistance evolution.
Variable recruitment of distal tuft dendrites shapes new hippocampal place fields
Authors: O’Hare Justin K. , Wang Jamie , Shala Margjele D. , Polleux Franck , Losonczy Attila
Published: February 2024

Hippocampal pyramidal neurons support episodic memory by integrating complementary information streams into new ‘place fields’. Distal tuft dendrites are widely thought to initiate place field formation by locally generating prolonged, globally-spreadingCa2+spikes known as plateau potentials. However, the hitherto experimental inaccessibility of distal tuft dendrites in the hippocampus has rendered theirin vivofunction entirely unknown. Here we gained direct optical access to this elusive dendritic compartment. We report that distal tuft dendrites do not serve as the point of origin for place field-forming plateau potentials. Instead, the timing and extent of peri-formation distal tuft recruitment is variable and closely predicts multiple properties of resultant place fields. Therefore, distal tuft dendrites play a more powerful role in hippocampal feature selectivity than simply initiating place field formation. Moreover, place field formation is not accompanied by globalCa2+influx as previously thought. In addition to shaping new somatic place fields, distal tuft dendrites possess their own local place fields. Tuft place fields are back-shifted relative to that of their soma and appear to maintain somatic place fields via post-formation plateau potentials. Through directin vivoobservation, we provide a revised dendritic basis for hippocampal feature selectivity during navigational learning.
Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution
Authors: Peters Anna L. , DePasquale Erica A.K. , Begum Gousia , Roskin Krishna M. , Woodle E. Steve , Hildeman David A.
Published: February 2024

Acute cellular rejection (ACR) affects >80% of pediatric liver transplant recipients within 5 years, and late ACR is associated with graft failure. Traditional anti-rejection therapy for late ACR is ineffective and has remained unchanged for six decades. Although CD8+ T cells promote late ACR, little has been done to define their specificity and gene expression. Here, we used single-cell sequencing and immune repertoire profiling (10X Genomics) on 30 cryopreserved 16G liver biopsies from 14 patients (5 pre-transplant or with no ACR, 9 with ACR). We identified expanded intragraft CD8+ T cell clonotypes (CD8EXP) and their gene expression profiles in response to anti-rejection treatment. Notably, we found that expanded CD8+clonotypes (CD8EXP) bore markers of effector and CD56hiCD161-‘NK-like’ T cells, retaining their clonotype identity and phenotype in subsequent biopsies from the same patients despite histologic ACR resolution. CD8EXPclonotypes localized to portal infiltrates during active ACR, and persisted in the lobule after histologic ACR resolution. CellPhoneDB analysis revealed differential crosstalk between KC and CD8EXPduring late ACR, with activation of the LTB-LTBR pathway and downregulation of TGFß signaling. Therefore, persistently-detected intragraft CD8EXPclones remain active despite ACR treatment and may contribute to long-term allograft fibrosis and failure of operational tolerance.

Graphical Abstract
Evidence for shallow cognitive maps in schizophrenia
Authors: Karagoz Ata B. , Moran Erin K. , Barch Deanna M. , Kool Wouter , Reagh Zachariah M.
Published: February 2024

Individuals with schizophrenia can have marked deficits in goal-directed decision making. Prominent theories differ in whether schizophrenia (SZ) affects the ability to exert cognitive control, or the motivation to exert control. An alternative explanation is that schizophrenia negatively impacts the formation of cognitive maps, the internal representations of the way the world is structured, necessary for the formation of effective action plans. That is, deficits in decision-making could also arise when goal-directed control and motivation are intact, but used to plan over ill-formed maps. Here, we test the hypothesis that individuals with SZ are impaired in the construction of cognitive maps. We combine a behavioral representational similarity analysis technique with a sequential decision-making task. This enables us to examine how relationships between choice options change when individuals with SZ and healthy age-matched controls build a cognitive map of the task structure. Our results indicate that SZ affects how people represent the structure of the task, focusing more on simpler visual features and less on abstract, higher-order, planning-relevant features. At the same time, we find that SZ were able to display similar performance on this task compared to controls, emphasizing the need for a distinction between cognitive map formation and changes in goal-directed control in understanding cognitive deficits in schizophrenia.
The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2
Authors: Guenthoer Jamie , Garrett Meghan E , Lilly Michelle , Depierreux Delphine M , Ruiz Felicitas , Chi Margaret , Stoddard Caitlin I , Chohan Vrasha , Sung Kevin , Ralph Duncan , Chu Helen Y , Matsen Frederick A , Overbaugh Julie
Published: February 2024

The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity for viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in the receptor binding domain of the S1 subunit of the spike glycoprotein have led to considerable escape from antibody responses, reducing the efficacy of vaccines and monoclonal antibody (mAb) therapies. Therefore, there is a need to interrogate more constrained regions of Spike, such as the S2 subdomain. Here, we describe a collection of S2 mAbs from two SARS-CoV-2 convalescent individuals that target multiple regions in the S2 subdomain and can be grouped into at least five epitope classes. Most did not neutralize SARS-CoV-2 with the exception of C20.119, which bound to a highly conserved epitope in the fusion peptide and showed broad binding and neutralization activity across SARS-CoV-2, SARS-CoV-1, and closely related zoonotic sarbecoviruses. Several of the S2 mAbs tested mediated antibody-dependent cellular cytotoxicity (ADCC) at levels similar to the S1 mAb S309 that was previously authorized for treatment of SARS-CoV-2 infections. Three of the mAbs with ADCC function also bound to spike trimers from HCoVs, such as MERS-CoV and HCoV-HKU1. Our findings suggest there are diverse epitopes in S2, including functional S2 mAbs with HCoV and sarbecovirus breadth that likely target functionally constrained regions of spike. These mAbs could be developed for potential future pandemics, while also providing insight into ideal epitopes for eliciting a broad HCoV response.
How were Hospitals Affected by the Ministry’s Release of Hospital Names to be Potentially Reorganized?
Authors: Takahashi Hiromichi , Shin Jung-ho , Kunisawa Susumu , Fushimi Kiyohide , Imanaka Yuichi
Published: February 2024

Background

The Japanese Ministry of Health, Labour and Welfare (MHLW) released a list of public and municipal hospitals (hereinafter “the list”) that are subject to reevaluation for hospital function. First, this study describes the functional differentiation status of Japanese hospital beds. Second, it evaluates the impact of the list release on the number of admissions in the listed hospitals.

Methods

Firstly, the number of hospitals and beds by the function of listed and non-listed hospitals in 2019 and 2021 were described using the bed function report. The Controlled Interrupted Time Series (CITS) analyses were subsequently conducted using Diagnosis Procedure Combination (DPC) data. Hospitals were divided near the cutoff point of the list. The outcomes were the number of admissions for gastrointestinal cancer surgery, those admitted via ambulance, or with a femoral fracture per 1,000 admissions. The exposure point was the week when the list was released.

Results

A decrease in the total number of beds was observed in 18.9% of the listed hospitals and 10.2% of others. Changes in bed functions were observed in 19.9% of the listed hospitals and 12.5% of others. CITS analyses showed that the rate ratio of admissions for gastrointestinal cancer surgery, those admitted via ambulance, and those with a femoral fracture in the listed hospital group after the list’s release were 1.001 (95% CI: 0.998–1.004, p = 0.619), 1.001 (95% CI: 0.998–1.004, p = 0.548), and 0.998 (95% CI: 0.998–1.002, p = 0.313), respectively.

Conclusion

More prominent trends of functional differentiation of hospital beds were observed in the listed hospitals. The release of the list did not impact the number of hospital admissions for gastrointestinal cancer surgery, those admitted via ambulance, or those with a femoral fracture per 1,000 admissions in the listed hospitals.
Cortical thickness and grey-matter volume anomaly detection in individual MRI scans: Comparison of two methods
Authors: Romascano David , Rebsamen Michael , Radojewski Piotr , Blattner Timo , McKinley Richard , Wiest Roland , Rummel Christian
Published: February 2024

Over the past decades, morphometric analysis of brain MRI has contributed substantially to the understanding of healthy brain structure, development and aging as well as to improved characterisation of disease related pathologies. Certified commercial tools based on normative modeling of these metrics are meanwhile available for diagnostic purposes, but they are cost intensive and their clinical evaluation is still in its infancy. Here we have compared the performance of “ScanOMetrics”, an open-source research-level tool for detection of statistical anomalies in individual MRI scans, depending on whether it is operated on the output of FreeSurfer or of the deep learning based brain morphometry tool DL+DiReCT. When applied to the public OASIS3 dataset, containing patients with Alzheimer’s disease (AD) and healthy controls (HC), cortical thickness anomalies in patient scans were mainly detected in regions that are known as predilection areas of cortical atrophy in AD, regardless of the software used for extraction of the metrics. By contrast, anomaly detections in HCs were up to twenty-fold reduced and spatially unspecific using both DL+DiReCT and FreeSurfer. Progression of the atrophy pattern with clinical dementia rating (CDR) was clearly observable with both methods. DL+DiReCT provided results in less than 25 minutes, more than 15 times faster than FreeSurfer. This difference in computation time might be relevant when considering application of this or similar methodology as diagnostic decision support for neuroradiologists.
Functional connectivity in preterm infants with intraventricular hemorrhage using fNIRS
Authors: Kebaya Lilian M. N. , Tang Lingkai , Altamimi Talal , Kowalczyk Alexandra , Musabi Melab , Roychaudhuri Sriya , Vahidi Homa , Meyerink Paige , Mayorga Paula Camila , de Ribaupierre Sandrine , Bhattacharya Soume , de Moraes Leandro Tristao Abi Ramia , Jurkiewicz Michael T. , St. Lawrence Keith , Duerden Emma G.
Published: February 2024

Introduction

Intraventricular hemorrhage (IVH) is a common neurological complication following very preterm birth. Resting-state functional connectivity (RSFC) using functional magnetic resonance imaging (fMRI) is associated with injury severity; yet fMRI is impractical for use in intensive care settings. Sensitive bedside neuroimaging biomarkers are needed to characterize injury patterns. Functional near-infrared spectroscopy (fNIRS) measures RSFC through cerebral hemodynamics and has greater accessibility. We aimed to determine comparability of RSFC in preterm infants with IVH using fNIRS and fMRI at term equivalent age (TEA), then examine fNIRS connectivity with the severity of IVH.

Methods

Very preterm born infants with IVH were scanned with both modalities at rest at TEA (postmenstrual age=37±0.92 weeks). Connectivity maps of IVH infants were compared between fNIRS and fMRI with the Euclidean and Jaccard distances. The severity of IVH in relation to fNIRS RSFC strength was examined using generalized linear models.

Results

fNIRS and fMRI RSFC maps showed good correspondence. At TEA, connectivity strength was significantly lower in healthy newborns (p-value = 0.023) and preterm infants with mild IVH (p-value = 0.026) compared to infants with moderate/severe IVH.

Conclusion

fNIRS has potential to be a new tool for assessing brain injury and monitoring cerebral hemodynamics and a promising marker for IVH severity in very preterm born infants.

Highlights

There is no previous study combining fNIRS and fMRI focused on preterm neonates with IVH.

This is the first study associating functional connectivity strength yielded from fNIRS with severity of IVH.

Good correspondence of functional connectivity was shown between fNIRS and fMRI.

Preterm neonates showed increased functional connectivity strength compared to healthy term born neonates. This can potentially be a marker for clinical assessment of severity of IVH.

fNIRS was demonstrated to have potential as a new bedside neuromonitoring tool for assessing early brain injuries of neonates.
Inflammatory proteins as strong predictors of death in COVID-19 patients with coexisting neurological diseases
Authors: Zielińska-Turek Justyna , Turek Grzegorz , Lyson Tomasz , Gajewski Jan , Ząbek Mirosław , Dorobek Małgorzata
Published: February 2024

Background

Although many studies published so far on COVID-19 have examined its clinical prognosis, there is still no universal laboratory test that can assess the risk of a fatal outcome in patients with coexisting neurological diseases.

Methods

The plasma concentrations of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, interleukin 6 (IL-6), D-dimers, and highly sensitive troponin I (hsTnI) were determined in a group of 400 consecutive in-patients with COVID-19 and concomitant neurological comorbidities.

Results

The median concentration levels of most of the inflammatory mediators/indicators, calculated for the whole group of patients, remained above the normal reference ranges, whereas the median concentrations of these substances were much higher in the sub-group of patients who died. Backward stepwise logistic regression confirmed the statistically significant predictors of death in a descending order of odds ratios as follows: LDH (3.8), ferritin (2.8), hsTnI (2.0), IL-6 (1.7), and age (1.01). A concentration of hsTnI > 64 ng/L appeared to constitute a strong predictor of an unfavorable prognosis. Patients who were treated with lopinavir and ritonavir, who required mechanical ventilation, and treatment with dexamethasone presented with significant increase in the concentrations of all the studied inflammatory proteins and increased odds ratio for death.

Conclusion

High plasma concentrations of pro-inflammatory proteins in patients suffering from COVID-19 and concomitant neurological diseases were associated with a more serious clinical course and an increased risk of death. The presence of these substances is worth monitoring as a valuable indicator of the current clinical condition of COVID-19 patients.
Innovative Approaches to Improve Knowledge of Zoonoses among Wildlife Hunters and Traders in Epe, Lagos, Nigeria: A Community Action Network-Based Intervention
Authors: Cadmus E , Awosanya E.J. , Adesokan H.K. , Akinseye V.O. , Olaleye F. , Morenikeji O , Fawole E.O. , Ansumana Rashid , Ayinmode K.O. , Oluwayelu D.O. , Cadmus S.
Published: February 2024

The West Africa One Health project is a multi-country project designed to utilise the One Health approach and deploy the Community Action Networks (CAN) to improve knowledge of high-risk communities on zoonoses. Majority of emerging zoonoses occur at the human-wildlife interface, of which wildlife hunters and traders are critical stakeholders. We assessed the effectiveness of a CAN-based intervention involving the use of a video documentary and case studies as model tools in improving the knowledge of zoonoses among wildlife hunters and traders in Epe, an established hunting community in Lagos State, Nigeria.

A quasi-experimental study design involving a total of 39 consenting registered wildlife stakeholders was adopted. A pre-tested, semi-structured, interviewer-administered questionnaire was used to obtain data on the participant’s sociodemographic characteristics, awareness level, and knowledge of zoonoses pre and post CAN-based intervention. Data were analysed using descriptive statistics McNemar and Wilcoxon Signed Ranks tests at a 5% level of significance.

The mean age of the participants was 46.7 ± 10.9 years. Most (76.9%) identified as male and had at least secondary education (89.7%). The number of participants who were aware that diseases could be contracted from animals and that it could be through inhalation and close contact increased significantly from 13 (33.3%), 2 (5.1%), and 9 (23.1%) pre-intervention to 37 (94.9 %), 11 (28.2%), and 21 (53.8%) post-intervention, respectively. The overall median knowledge score increased significantly from 1 (Interquartile range (IQR): 0 – 2) pre-intervention to 3 (IQR: 2 – 4) post-intervention.

The CAN-based intervention involving the use of a video documentary and case studies as model tools was effective in improving the knowledge of zoonoses among wildlife hunters and traders in the hunting community and may be beneficial for future practice.
Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance
Authors: Dumitrascu Oana M. , Doustar Jonah , Fuchs Dieu-Trang , Koronyo Yosef , Sherman Dale S. , Miller Michelle Shizu , Johnson Kenneth O. , Carare Roxana O. , Verdooner Steven R. , Lyden Patrick D. , Schneider Julie A. , Black Keith L. , Koronyo-Hamaoui Maya
Published: February 2024

Introduction

The vascular contribution to Alzheimer’s disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition.

Methods

Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects. Perivascular AP burden among cognitive states was correlated with neuroimaging and cognitive measures.

Results

Peri-arteriolar exceeded peri-venular AP count (p<0.0001). Secondary branch AP count was significantly higher in cognitively impaired (p<0.01). Secondary small and tertiary peri-venular AP count strongly correlated with clinical dementia rating, hippocampal volumes, and white matter hyperintensity count.

Discussion

Our topographic analysis indicates greater retinal amyloid accumulation in the retinal peri-arteriolar regions overall, and distal peri-venular regions in cognitively impaired individuals. Larger longitudinal studies are warranted to understand the temporal-spatial relationship between vascular dysfunction and perivascular amyloid deposition in AD.

Highlights:

Retinal peri-arteriolar region exhibits more amyloid compared with peri-venular regions.

Secondary retinal vascular branches have significantly higher perivascular amyloid burden in subjects with impaired cognition, consistent across sexes.

Cognitively impaired individuals have significantly greater retinal peri-venular amyloid deposits in the distal small branches, that correlate with CDR and hippocampal volumes.
Liquid phase electron microscopy of bacterial ultrastructure
Authors: Caffrey Brian J. , Pedrazo-Tardajos Adrián , Liberti Emanuela , Gaunt Ben , Kim Judy S. , Kirkland Angus I.
Published: February 2024

Recent advances in liquid phase scanning transmission electron microscopy (LP-STEM) have enabled the study of dynamic biological processes at nanometre resolutions, paving the way for live-cell imaging using electron microscopy. However, this technique is often hampered by the inherent thickness of whole cell samples and damage from electron beam irradiation. These restrictions degrade image quality and resolution, impeding biological interpretation. Here we detail the use of graphene encapsulation, STEM, and energy-dispersive X-ray (EDX) spectroscopy methods to mitigate these issues, providing unprecedented levels of intracellular detail in aqueous specimens. This work demonstrates the potential of LP-STEM to examine and identify internal cellular structures in thick biological samples, in a radiation resistant, gram-positive bacterium, Deinococcus radiodurans using a variety of imaging techniques.
Near telomere-to-telomere genome assemblies of two Chlorella species unveil the composition and evolution of centromeres in green algae
Authors: Wang Bo , Jia Yanyan , Dang Ningxin , Yu Jie , Bush Stephen J. , Gao Shenghan , He Wenxi , Wang Sirui , Guo Hongtao , Yang Xiaofei , Ma Weimin , Ye Kai
Published: February 2024

Background: Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown. Results: We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions. Conclusions: This study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.
Electrophysiological approaches to understanding brain-muscle interactions during gait: a systematic review
Authors: Seynaeve Maura , Mantini Dante , de Beukelaar Toon T
Published: February 2024

Objective: This study systematically reviews the role of the cortex in gait control by analyzing connectivity between electroencephalography (EEG) and electromyography (EMG) signals, i.e. neuromuscular connectivity (NMC) during walking. We aim to answer the following questions: (i) Is there significant NMC during gait in a healthy population? (ii) Is NMC modulated by gait task specifications (e.g. speed, surface, additional task demands)? (iii) Is NMC altered in the elderly or a population affected by a neuromuscular or neurologic disorder? Methods: Following PRISMA guidelines, a systematic search of seven scientific databases was conducted until September 2023. Results: Out of 1308 identified papers, 27 studies met the eligibility criteria. Despite large variability in methodology, significant NMC was detected in most of the studies. NMC was able to discriminate between a healthy population and a population affected by a neuromuscular or neurologic disorder. Tasks requiring higher sensorimotor control resulted in an elevated level of NMC. Conclusions: While NMC holds promise as a metric for advancing our comprehension of brain-muscle interactions during gait, aligning methodologies across studies is imperative. Significance: Analysis of NMC provides valuable insights for the understanding of neural control of movement, development of gait retraining programs and contributes to advancements in neurotechnology.
Reconstructing Voice Identity from Noninvasive Auditory Cortex Recordings
Authors: Lamothe Charly , Thoret Etienne , Trapeau Régis , Giordano Bruno L. , Sein Julien , Takerkart Sylvain , Ayache Stéphane , Artières Thierry , Belin Pascal
Published: February 2024

The cerebral processing of voice information is known to engage, in human as well as non-human primates, “temporal voice areas” (TVAs) that respond preferentially to conspecific vocalizations. However, how voice information is represented by neuronal populations in these areas, particularly speaker identity information, remains poorly understood. Here, we used a deep neural network (DNN) to generate a high-level, small-dimension representational space for voice identity—the ‘voice latent space’ (VLS)—and examined its linear relation with cerebral activity via encoding, representational similarity, and decoding analyses. We find that the VLS maps onto fMRI measures of cerebral activity in response to tens of thousands of voice stimuli from hundreds of different speaker identities and better accounts for the representational geometry for speaker identity in the TVAs than in A1. Moreover, the VLS allowed TVA-based reconstructions of voice stimuli that preserved essential aspects of speaker identity as assessed by both machine classifiers and human listeners. These results indicate that the DNN-derived VLS provides high-level representations of voice identity information in the TVAs.
Transcriptomic characterization of recombinantClostridium beijerinckiiNCIMB 8052 expressing methylglyoxal synthase and glyoxal reductase fromClostridium pasteurianumATCC 6013
Authors: Kumar Santosh , Agyeman-Duah Eric , Ujor Victor C.
Published: February 2024

Bioconversion of abundant lactose-replete whey permeate to value added chemicals holds promise for valorization of this increasing food processing waste. Efficient conversion of whey-permeate-borne lactose requires adroit microbial engineering to funnel carbon to the desired chemical. Having engineered a strain ofClostridium beijerinckiiNCIMB 8052 (C. beijerinckii_mgsA+mgR) that produces 87% more butanol on lactose than the control strain, in this study, we deployed RNA sequencing to profile the global transcriptome ofC. beijerinckii_mgsA+mgR. The results revealed broadly contrasting gene expression patterns inC. beijerinckii_mgsA+mgR relative to the control strain. These were characterized by widespread downregulation of Fe-S proteins inC. beijerinckii_mgsA+mgR, coupled with increased expression of lactose uptake and catabolic genes, iron and phosphate uptake genes, two component signal transduction and motility genes, and genes involved in the biosynthesis of vitamin B5and B12, aromatic amino acids, particularly tryptophan; arginine, and pyrimidines. Conversely, L-aspartate-dependentde novobiosynthesis of NAD as well as biosynthesis/metabolism of glycine, threonine, lysine, isoleucine and asparagine were downregulated. Furthermore, genes involved in cysteine and methionine biosynthesis and metabolism, including cysteine desulfurase—a central player in Fe-S cluster biosynthesis—were equally downregulated. Genes involved in biosynthesis of capsular polysaccharides and stress response were also downregulated inC. beijerinckii_mgsA+mgR. The results suggest that remodeling of cellular and metabolic networks inC. beijerinckii_mgsA+mgR to counter likely effect of methylglyoxal production following heterologous expression of methyl glyoxal synthase led to enhanced growth and butanol production inC. beijerinckii_mgsA+mgR.

IMPORTANCE

Biological production of commodity chemicals from abundant waste streams such as whey permeate represents a rational approach for decarbonizing chemical production. Whey permeate remains a vastly underutilized feedstock for bioproduction purposes. Thus, enhanced understanding of the cellular and metabolic repertoires of lactose-mediated production of chemicals such as butanol, promises to arm researchers with new engineering targets that can be fine-tuned in recombinant and native microbial strains to engender stronger coupling of whey permeate-borne lactose to value-added chemicals. Our results highlight new genetic targets for future engineering ofC. beijerinckii_mgsA+mgR and indeed,C. beijerinckiifor improved butanol production on lactose, and ultimately in whey permeate.
New approaches to the Single-Interval Adjustment Matrix (SIAM) Yes-No task
Authors: Shepherd Daniel , Hautus Michael J.
Published: February 2024

Two adaptations of the Single-Interval Adjust-Matrix Yes-No (SIAM-YN) task, designed to increase the efficiency of absolute threshold estimation, are described. The first, the SIAM Twin Track (SIAM-TT) task, consists of two interleaved tracks of the standard SIAM-YN that are run in the same trial with a single response. The second new task modifies the binary SIAM-YN task by using a six-point rating-scale (SIAM-Rating). In Experiment 1, data from three tasks estimating absolute thresholds were obtained using a 10-ms tone, the 2-IFC transformed up-down procedure, SIAM-YN task, and the SIAM-TT task. The data support the use of the SIAM-TT as an alternative to the conventional two-interval and one-interval (SIAM-YN) tasks when used to estimate absolute thresholds. By presenting two interleaved SIAM-YN tracks on a single experimental trial, the SIAM-TT task possesses greater efficiency alongside its signal-detection heritage which confers less response bias. Similarly, in Experiment 2, which compared the 2-IFC adaptive, SIAM-YN, and SIAM-Rating tasks, there was no main effect of task upon threshold estimates. The findings replicate previous studies supporting the validity and efficiency of the SIAM-YN task, and extends the SIAM-YN toolbox to efficiently facilitate the generation of psychometric functions (the SIAM-TT task) and Receiver Operating Characteristic Curves (the SIAM-Rating task).
Glucose appetition in C57BL/6J mice: Influence of nonnutritive sweetener experience, food deprivation state and sex differences
Authors: Sclafani Anthony , Ackroff Karen
Published: February 2024

In addition to its sweet taste, glucose has potent and rapid postoral actions (appetition) that enhance its reward value. This has been demonstrated by the experience-induced preference for glucose over initially preferred nonnutritive sweetener solutions in 24-h choice tests. However, some sweetener solutions (e.g., 0.8% sucralose) have inhibitory postoral actions that may exaggerate glucose appetition whereas others (e.g., 0.1% sucralose + 0.1% saccharin, S+S) do not. Experiment 1 revealed that food-restricted (FR) male C57BL/6J mice displayed similar rapid glucose appetition effects (stimulation of glucose licking within minutes) and conditioned flavor preferences following 1-h experience with flavored 0.8% sucralose or 0.1% S+S and 8% glucose solutions. Thus, the inhibitory effects of 0.8% sucralose observed in 24-h tests were not apparent in 1-h tests. Experiment 2 evaluated the effects of food deprivation state on 1-h glucose appetition. Unlike FR female mice, ad libitum (AL) fed mice displayed no or delayed stimulation of glucose licking depending upon the training solutions used (0.1% S+S vs. 8% glucose, or 0.2% S+S vs. 16% glucose). Both AL groups, like the FR group, developed a preference for the glucose-paired flavor over the S+S paired flavor. Thus, food restriction promotes glucose appetition but is not required for a conditioned preference. Overall, male and female mice showed similar glucose appetition responses although females displayed a more rapid initial glucose response.
Meta-analysis of the human gut microbiome uncovers shared and distinct microbial signatures between diseases
Authors: Jin Dong-Min , Morton James T. , Bonneau Richard
Published: February 2024

Microbiome studies have revealed gut microbiota’s potential impact on complex diseases. However, many studies often focus on one disease per cohort. We developed a meta-analysis workflow for gut microbiome profiles and analyzed shotgun metagenomic data covering 11 diseases. Using interpretable machine learning and differential abundance analysis, our findings reinforce the generalization of binary classifiers for Crohn’s disease (CD) and colorectal cancer (CRC) to hold-out cohorts and highlight the key microbes driving these classifications. We identified high microbial similarity in disease pairs like CD vs ulcerative colitis (UC), CD vs CRC, Parkinson’s disease vs type 2 diabetes (T2D), and schizophrenia vs T2D. We also found strong inverse correlations in Alzheimer’s disease vs CD and UC. These findings detected by our pipeline provide valuable insights into these diseases.

IMPORTANCE

Assessing disease similarity is an essential initial step preceding disease-based approach for drug repositioning. Our study provides a modest first step in underscoring the potential of integrating microbiome insights into the disease similarity assessment. Recent microbiome research has predominantly focused on analyzing individual disease to understand its unique characteristics, which by design excludes comorbidities individuals. We analyzed shotgun metagenomic data from existing studies and identified previously unknown similarities between diseases. Our research represents a pioneering effort that utilize both interpretable machine learning and differential abundance analysis to assess microbial similarity between diseases.
Robust variability of grid cell properties within individual grid modules enhances encoding of local space
Authors: Redman William T. , Acosta-Mendoza Santiago , Wei Xue-Xin , Goard Michael J.
Published: February 2024

Although grid cells are one of the most well studied functional classes of neurons in the mammalian brain, whether there is a single orientation and spacing value per grid module has not been carefully tested. We analyze a recent large-scale recording of medial entorhinal cortex to characterize the presence and degree of heterogeneity of grid properties within individual modules. We find evidence for small, but robust, variability and hypothesize that this property of the grid code could enhance the encoding of local spatial information. Performing analysis on synthetic populations of grid cells, where we have complete control over the amount heterogeneity in grid properties, we demonstrate that grid property variability of a similar magnitude to the analyzed data leads to significantly decreased decoding error. This holds even when restricted to activity from a single module. Our results highlight how the heterogeneity of the neural response properties may benefit coding and opens new directions for theoretical and experimental analysis of grid cells.
Synchronized photoactivation of T4K rhodopsin causes a chromophore-dependent retinal degeneration that is moderated by interaction with phototransduction cascade components
Authors: Tam Beatrice M. , Burns Paloma , Chiu Colette N. , Moritz Orson L.
Published: February 2024

Multiple mutations in theRhodopsingene cause sector retinitis pigmentosa in humans and a corresponding light-exacerbated retinal degeneration (RD) in animal models. Previously we have shown that therhodopsinmutation T4K requires photoactivation to exert its toxic effect. Here we further investigated the mechanisms involved in rod cell death caused by T4K rhodopsin inXenopus laevis. In this model, RD was prevented by rearing animals in constant darkness but surprisingly also in constant light. RD was maximized by light cycles containing at least one hour of darkness and 20 minutes of light exposure, light of intensity 750 lux or greater, and by sudden light onset. Under conditions of frequent light cycling, RD occured rapidly and synchronously, with massive shedding of ROS fragments into the RPE initiated within hours, and subsequent death and phagocytosis of rod cell bodies. RD was minimized by reduced light levels, pre-treatment with constant light, and gradual light onset. RD was prevented by genetic ablation of the retinal isomerohydrolase RPE65, and exacerbated by ablation of phototransduction components GNAT1, SAG, and GRK1. Our results indicate that photoactivated T4K rhodopsin is toxic, that cell death requires synchronized photoactivation of T4K rhodopsin, and that toxicity is mitigated by interaction with other rod outer segment proteins regardless of whether they participate in activation or shutoff of phototransduction. In contrast, RD caused by P23H rhodopsin does not require photoactivation of the mutant protein, as it was exacerbated by RPE65 ablation, suggesting that these phenotypically similar disorders may benefit from different treatment strategies.

Significance

A large number ofrhodopsinmutations are linked to the inherited degenerative disease retinitis pigmentosa. Although the end result in each case is the loss of photoreceptor cells and blindness, not all of these mutations cause cell death via the same mechanism. In order to design and test treatment therapies that target the disease at points as upstream as possible in the process, we require detailed understanding of the range and nature of these disease mechanisms. This study using a transgenicXenopus laevismodel has extended our understanding of how T4K rhodopsin and related mutations cause rod cell photoreceptor death via a phototoxic product, and how this mechanism differs from the more extensively researched protein misfolding mechanism underlying cell death caused by P23H rhodopsin.
Failed stopping transiently suppresses the electromyogram in task-irrelevant muscles
Authors: Mills Isaiah , Fisher Mitchell , Wadsley Corey , Greenhouse Ian
Published: February 2024

Selectively stopping individual parts of planned or ongoing movements is an everyday motor skill. For example, while walking in public you may stop yourself from waving at a stranger who you mistook for a friend while continuing to walk. Despite its ubiquity, our ability to selectively stop actions is limited. Canceling one action can delay the execution of other simultaneous actions. This stopping-interference effect on continuing actions during selective stopping may be attributed to a global inhibitory mechanism with widespread effects on the motor system. Previous studies have characterized a transient global reduction in corticomotor excitability by combining brain stimulation with electromyography (EMG). Here, we examined whether global motor inhibition during selective stopping can be measured peripherally and with high temporal resolution using EMG alone. Eighteen participants performed a bimanual anticipatory response inhibition task with their index fingers while maintaining a tonic contraction of the task-irrelevant abductor digiti minimi (ADM) muscles. A time series analysis of the ADM EMG signal revealed transient inhibition during failed stopping compared to go response trials 150 ms to 203 ms following the stop signal. The pattern was observed in both hands during bimanual stop-all trials as well as selective stop-left and stop-right trials of either hand. These results indicate that tonic muscle activity is sensitive to the effects of global motor suppression even when stopping fails. Therefore, EMG can provide a physiological marker of global motor inhibition to probe the time course and extent of stopping processes.

Key Points

Successfully stopping an initiated response globally suppresses the motor system.

Using electromyography of tonic muscle activity, we show inhibition spills over to task-irrelevant muscles during failed stopping.

The electromyographic pattern of inhibition is transient, lasting from approximately 150 to 203 ms following a stop signal when stopping fails.

The time course of the peripheral suppression of muscle activity may be leveraged to more precisely examine candidate neural mechanisms.

This non-invasive measure of motor system inhibition may be useful for tracking inhibitory control deficits in clinical populations.
A computational and multi-brain signature for aberrant social coordination in schizophrenia
Authors: Wang Ya-Jie , Wen Yalan , Zheng Leilei , Chen Ji , Lin Zheng , Pan Yafeng
Published: February 2024

Social functioning impairment is a core symptom of schizophrenia (SCZ). Yet, the computational and neural mechanisms of social coordination in SCZ under real-time and naturalistic settings are poorly understood. Here, we instructed patients with SCZ to coordinate with a healthy control (HC) in a joint finger-tapping task, during which their brain activity was measured by functional near-infrared spectroscopy simultaneously. The results showed that patients with SCZ exhibited poor rhythm control ability and unstable tapping behaviour, which weakened their interpersonal synchronization when coordinating with HCs. Moreover, the dynamical systems modelling revealed disrupted between-participant coupling when SCZ patients coordinated with HCs. Importantly, increased inter-brain synchronization was identified within SCZ-HC dyads, which positively correlated with behavioural synchronization and successfully predicted dimensions of psychopathology. Our study suggests that SCZ individuals may require stronger neural alignment to compensate for deficiency in their coordination ability. This hyperalignment may be relevant for developing inter-personalized treatment strategies.
Effectiveness of DiabeText, a mHealth intervention to support diabetes self-management: randomized controlled trial in primary care
Authors: Zamanillo-Campos Rocío , Fiol-Deroque Maria Antonia , Serrano-Ripoll Maria Jesús , Llobera-Canaves Joan , Taltavull-Aparicio Joana María , Leiva-Rus Alfonso , Ripoll-Amengual Joana , Angullo-Martínez Escarlata , Socias-Buades Isabel Maria , Masmiquel Luis , Konieczna Jadwiga , Zaforteza-Dezcallar María , Boronat-Moreiro Maria Asunción , Mira-Martínez Sofía , Gervilla-García Elena , Ricci-Cabello Ignacio
Published: February 2024

Background

Complications arising from uncontrolled Type 2 Diabetes (T2D) poses a significant burden on individuals’ well-being and healthcare resources. Digital interventions may play a key role in mitigating such complications by supporting patients to adequately self-manage their condition.

Aim

To assess the impact of DiabeText, a new theory-based, patient-centered, mobile health intervention integrated with electronic health records to send tailored short text messages to support T2D self-management.

Design and setting

Pragmatic, phase III, 12-month, two-arm randomized clinical trial with T2D primary care patients in Spain.

Method

742 participants with suboptimal glycemic control (HbA1c>7.5) were randomly allocated to a control (usual care) or intervention (DiabeText) group. The DiabeText group received, in addition to usual care, 165 messages focused on healthy lifestyle and medication adherence. Primary outcome: glycated hemoglobin (HbA1c). Secondary outcomes: medication possession ratio, quality of life (EQ-5D-5L), diabetes self-efficacy (DSES); and self-reported adherence to medication, Mediterranean diet (MEDAS-14), and physical activity (IPAQ).

Results

At 12 months follow-up, no statistically significant differences in mean HbA1c were observed between the intervention (7.5 [95%CI 6.7 to 8.2]) and control groups (7.4 [6.7 to 8.3]). In comparison with the control group, the DiabeText group showed significant (p<0.05) improvements in self-reported medication adherence (OR=1.4; 95%CI: 1.0 to 1.9), DSES (Cohen’s d=0.4), and EQ5D-5L (Cohen’s d=0.2) scores; but not in the rest of secondary outcomes.

Conclusion

DiabeText successfully improved quality of life, diabetes self-management, and self-reported medication adherence in primary care patients with T2D. Further research is needed to enhance its effects on physiological outcomes.
Sleep Hygiene Index: Dimensionality, internal consistency, and nomological validity among Colombian medical students
Authors: Campo-Arias Adalberto , Pedrozo-Pupo John Carlos , Caballero-Domínguez Carmen Cecilia
Published: February 2024

Background and purpose

A new version of the Sleep Hygiene Index (SHI-10) has recently been introduced, and the psychometric performance in other populations is unknown. This study aimed to determine the dimensionality, internal consistency, and nomological validity of the SHI-10 among medical students at a Colombian university.

Methods

A psychometric study was designed to determine indicators of validity (construct and nomological) and reliability (internal consistency) in which 309 medical students between 18 and 39 years (M=20.83, SD=2.68), and 54.69% were female. Construct validity (dimensionality) was tested through confirmatory factor analysis, internal consistency with Cronbach’s alpha and McDonald’s omega coefficients, and nomological validity through correlations with the Athens Insomnia Scale, Epworth Somnolence Scale, Generalized Anxiety Disorder (GAD)-7) and Patient Health Questionnaire (PHQ-9).

Results

The four-dimensional structure of the SHI-10 showed adequate indicators of goodness of fit (Satorra-Bentler’s chi-square of 43.30 [df of 29, p=.04], chi-square/df of 1.49, RMSEA of .04 [90%CI .01-.06], CFI of .97, TLI of .96 and SRMR .04). The four dimensions of the SHI-10 showed values less than .70 and limited nomological validity (most Pearson correlations were less than .30).

Conclusions

The SHI-10 shows a four-dimensional structure of SHI-10; however, the four dimensions of the SHI-10 present low internal consistency and limited nomological validity. More studies are needed to show the psychometric performance of the SHI-10.