bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete genome sequencing ofBacillus subtilis(CWTS 5), a siderophore-producing bacterium triggers antagonistic potential againstRalstonia solanacearum
Authors: Chandwani Sapna , Dewala Sahabram , Chavan Sonal Manik , Paul Dhiraj , Pachaiappan Raman , Gopi Muthukaruppan , Amaresan Natarajan
Published: April 2023

Aim

The aims of this study were to explore the antagonistic potential of siderophore-producing Bacillus subtilis (CWTS 5) for the suppression of Ralstonia solanacearum and to explore the mechanisms of inhibition by FTIR, LC-MS, and whole genome analysis.

Methods and Results

A siderophore-producing B. subtilis (CWTS 5) possessing several plant growth-promoting properties such as IAA and ACC deaminase production, phosphate solubilization, and nitrogen fixation was assessed for its inhibitory effect against R. solanacearum, and its mechanisms were explored by in vitro and in vivo analyses. The active secondary metabolites in the siderophore extracts were identified as 2-deoxystreptamine, miserotoxin, fumitremorgin C, pipercide, pipernonaline, gingerone A, and deoxyvasicinone by LC-MS analysis. The Arnow's test and antiSMASH analysis confirmed the presence of catecholate siderophores, and the functional groups determined by FTIR spectroscopy confirmed the presence of secondary metabolites in the siderophore extract possessing antagonistic effect. The complete genome sequence of CWTS 5 revealed the gene clusters responsible for siderophore, antibiotics, secondary metabolite production, and antibacterial and antifungal metabolites. Furthermore, the evaluation of CWTS 5 against R. solanacearum in pot studies demonstrated 40.0% reduced disease severity index (DSI) by CWTS 5, methanolic extract (DSI-26.6%), ethyl acetate extract (DSI-20.0%), and increased plant growth such as root and shoot length, wet weight and dry weight of Solanum lycopersicum L. owing to its antagonistic potential. This genomic insight will support future studies on the application of B. subtilis as a plant growth promoter and biocontrol agent against R. solanacearum for bacterial wilt management.

Conclusion

The results of this study revealed that B. subtilis (CWTS 5) possesses multiple mechanisms that control R. solanacearum, reduce disease incidence, and improve S. lycopersicum growth.
Review and Critical Appraisal of Clinical Practice Guidelines of Modalities Used in the Diagnosis of Celiac Disease
Authors: Graham Kennedy , Gidrewicz Dominica , Turner Justine M , Duerksen Donald R , Pinto-Sanchez Maria Ines
Published: April 2023

Background

There is controversy over the recommendations for specific serological strategies implemented and the need for a biopsy to confirm celiac disease (CeD). We reviewed and appraised the current clinical practice guidelines (CPGs) to assess the quality and reliability of recommendations for CeD diagnosis in pediatric and adult populations.

Methods

We searched databases, including MEDLINE, EMBASE, Web of Science, and CINAHL, between December 2010 and January 2021 for CPGs. Four independent reviewers extracted data. Appraisal of Guidelines Research and Evaluation (AGREE II) criteria were applied by two reviewers, and a standardized score was calculated for each of the six domains. A cut-off of 60% was used to identify high-quality guidelines.

Results

A total of 654 records were identified, 10 of which were eligible for data extraction. Both adult and pediatric CPGs averaged above 70% for the domains of ‘scope and purpose’ and ‘clarity and presentation’. For ‘stakeholder involvement’, the mean adult and pediatric CPG scores were below the cut-off. Only one adult-focused guideline exceeded the cut-off for the ‘rigour of development’ domain. ‘Applicability’ scores were most alarming, with adult CPGs averaging 21% and pediatric CPGs averaging 23%.

Conclusion

Our review and appraisal of the CPGs for the diagnosis of CeD highlight significant discrepancies in clinical recommendations and some concerns regarding methodological rigour, particularly in stakeholder engagement, rigour, and applicability. Creating a Canadian guideline of high methodological quality that overcomes these weaknesses is critical to optimize patient care and ensuring accurate diagnoses in CeD.
Inspiring Regime Change
Authors: Morris Stephen , Shadmehr Mehdi
Published: April 2023

We consider the problem of a leader who can assign rewards for citizens for different anti-regime actions. Citizens face a coordination problem in which each citizen has a private, endogenous degree of optimism about the likelihood of regime change. Because more optimistic citizens are easier to motivate, the choice of optimal rewards entails optimal screening. This leads to a distribution of anti-regime actions. A key result is the emergence of a vanguard, consisting of citizens who engage in the endogenous, maximum level of action. Other citizens participate at varying degrees, with less optimistic citizens contributing less. We explore how the regime’s strength or the maximum reward available to the leader influences the distribution of actions. Moreover, we show that more heterogeneity (e.g., higher inequality) among potential revolutionaries reduces the likelihood of regime change. Our methodological contribution is that we deliver a sharp and novel marriage of screening and global games.
The Military Medical Officer’s Current-Day Professional Identity: An Enhanced Model
Authors: Cole Rebekah , Williamson Samantha S , Hughes Joshua R , Rudinsky Sherri L
Published: April 2023

Background

As the landscapes of war have evolved, so too has the role of the military medical officer (MMO). Colonel (Retired) Barry Wolcott developed a “vector” model in the 1990s, illustrating the dual professional role of the MMO. Since then, propelled by the War on Terror, MMOs have adapted to treating patients in volatile, uncertain, complex, and ambiguous operational environments. This study, therefore, aimed to explore modern-day aspects of the MMO’s role in order to enhance Wolcott’s depiction of the MMO’s professional identity in contemporary operational environments.

Materials and Methods

We used the qualitative phenomenological tradition to design our study. We interviewed military physicians from a variety of specialties in order to explore their experiences and professional identity as MMOs. Our research team then coded each of these interview transcripts. We organized these codes into categories, which served as the themes of our study.

Results

The following themes emerged from our data regarding the role of the MMO in the operational environment: Primary roles (officer, physician, educator, and diplomat) and aptitudes (innovation, advocacy, cultural competency, and leadership). The MMO’s roles as officer and physician often intersect, with dual foci on the mission and the patient. The MMO also serves as an educator to medics and line officers. In addition, they act as diplomats both outside and within the military. Within each of these primary roles, the MMO innovatively prepares for future landscapes of war and advocates for both the individual warfighter and the unit/command. Finally, the MMO navigates both foreign and internal cultural differences and demonstrates leadership in enabling the military’s mission.

Conclusions

The role of the MMO is complex and multifaceted. The recognition of the contemporary MMO’s unique skill set is essential for the effective education and training of future military health care leaders. The value of capitalizing on this unique skill set has been demonstrated in recent civ-mil responses. Because their intricate skill set is specialized for the operational environment, long-term retention of MMOs is key to force readiness.
The Internal Morality of Criminal Law
Authors: Edwards James , Yusari Tarek
Published: April 2023

According to a popular picture, criminal law lives up to the demands of its internal morality when its norms have counterparts with the same content in morality—when it conforms to what we call the mirror principle. This article argues that the popular picture must be redrawn by relying on a second principle, which we call the instrumental principle. Criminal law conforms to the instrumental principle when the existence of its norms helps to prevent or ameliorate moral wrongdoing. Our argument is that the instrumental principle forms part of the internal morality of criminal law, and supplies a justification for criminal laws that depart from the mirror principle. We further suggest that criminal law’s internal morality is asymmetrical: though departures from the mirror principle are sometimes justified by the instrumental principle, departures from the latter are not justified by the former.
Model of Human Fallibility: Traveling Behavioral Assumptions in Public Governance
Authors: Pallesen Trine , Pedersen Kirstine Zinck
Published: April 2023

Over the past decades, insights from behavioral sciences have gained traction as sources for designing public policy and for governing areas of collective concerns. It has become increasingly common to ascribe ‘flawed’ decision-making to systematic heuristics and cognitive biases of citizens and experts. This popular behavioral approach to public organizing is anchored in a very particular model of human behavior, namely what we label homo fallibilis or the model human fallibility. This model grew out of a critique of neoclassical economics’ homo economicus but ended as a new recipe for predicting and regulating human behavior. To conceptualize the model of human fallibility and to understand its ability to travel intellectually and empirically, we trace it historically to Simon’s bounded rationality, over Tversky and Kahneman’s systematic biases and to recent nudge literature. Next, we illustrate how and by what means the model travels into different areas of public service provision in strikingly similar ways. We finally suggest that the model of human fallibility risks giving way to an “anti-human stance” that promotes a particular type of behavioral design in ever more areas of public governance at the expense of alternative ways of governing that enhance discretion, expertise, training, and habituation.
Single-cell and spatially resolved transcriptomics for liver biology
Authors: Lin Ping , Yan Xi , Jing Siyu , Wu Yanhong , Shan Yiran , Guo Wenbo , Gu Jin , Li Yu , Zhang Haibing , Li Hong
Published: April 2023

Single-cell transcriptomics enables the identification of rare cell types and the inference of state transitions, whereas spatially resolved transcriptomics allows the quantification of cells and genes in the context of tissues. The recent progress in these new technologies is improving our understanding of the cell landscape and its roles in diseases. Here, we review key biological insights into liver homeostasis, development, regeneration, chronic liver disease, and cancer obtained from single-cell and spatially resolved transcriptomics. We highlight recent progress in the liver cell atlas that characterizes the comprehensive cellular composition; diversity and function; the spatial architecture such as liver zonation, cell communication, and proximity; the cell identity conversion and cell-specific alterations that are associated with liver pathology; and new therapeutic targets. We further discuss outstanding challenges, advanced experimental technologies, and computational methods that help to address these challenges.
High fat diet allows food-predictive stimuli to energize action performance in the absence of hunger, without distorting insulin signaling on accumbal cholinergic interneurons
Authors: Gladding Joanne M. , Lingawi Nura W. , Leung Beatrice , Kendig Michael D. , Chieng Billy C. , Laurent Vincent
Published: April 2023

Obesity can disrupt how food-predictive stimuli control action performance and selection. These two forms of control recruit cholinergic interneurons (CIN) located in the nucleus accumbens core (NAcC) and shell (NAcS), respectively. Given that obesity is associated with insulin resistance in this region, we examined whether interfering with CIN insulin signaling disrupts how food-predictive stimuli control actions. To interfere with insulin signaling we used a high-fat diet (HFD) or genetic excision of insulin receptor (InsR) from cholinergic cells. HFD left intact the capacity of food-predictive stimuli to energize performance of an action earning food when mice were tested hungry. However, it allowed this energizing effect to persist when the mice were tested sated. This persistence was linked to NAcC CIN activity but was not associated with distorted CIN insulin signaling. Accordingly, InsR excision had no effect on how food-predicting stimuli control action performance. Next, we found that neither HFD nor InsR excision altered the capacity of food-predictive stimuli to guide action selection. Yet, this capacity was associated with changes in NAcS CIN activity. These results indicate that insulin signaling on accumbal CIN does not modulate how food-predictive stimuli control action performance and selection. However, they show that HFD allows food-predictive stimuli to energize performance of an action earning food in the absence of hunger.
Stress-induced clustering of the UPR sensor IRE1α is driven by disordered regions within its ER lumenal domain
Authors: Kettel Paulina , Marosits Laura , Spinetti Elena , Rechberger Michael , Radler Philipp , Niedermoser Isabell , Fischer Irmgard , Versteeg Gijs A , Loose Martin , Covino Roberto , Karagöz G Elif
Published: April 2023

Upon accumulation of unfolded proteins at the endoplasmic reticulum (ER), IRE1 activates the unfolded protein response (UPR) to restore protein-folding homeostasis. During ER stress, IRE1’s ER lumenal domain (LD) drives its clustering on the ER membrane to initiate signaling. How IRE1’s LD assembles into high-order oligomers remains largely unknown. Byin vitroreconstitution experiments we show that human IRE1α LD forms dynamic biomolecular condensates. IRE1α LD condensates were stabilized when IRE1α LD was tethered to model membranes and upon binding of unfolded polypeptide ligands. Molecular dynamics simulations suggested that weak multivalent interactions are involved in IRE1α LD assemblies. Mutagenesis showed that disordered regions in IRE1α LD control its clusteringin vitroand in cells. Importantly, dysregulated clustering led to defects in IRE1α signaling. Our results reveal that membranes and unfolded polypeptides act as scaffolds to assemble dynamic IRE1α condensates into stable, signaling competent clusters.
Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration
Authors: Bryson Noah , Lombardi Lorenzo , Hawthorn Rachel , Fei Jie , Keesey Rodolfo , Peiffer J.D. , Seáñez Ismael
Published: April 2023

Objective

Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation.

Approach

In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS.

Results

Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle-specific motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode’s position.

Significance

Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.
Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis
Authors: Spaas Jan , Van der Stede Thibaux , de Jager Sarah , van de Waterweg Berends Annet , Tiane Assia , Baelde Hans , Baba Shahid P. , Eckhardt Matthias , Wolfs Esther , Vanmierlo Tim , Hellings Niels , Eijnde Bert O. , Derave Wim
Published: April 2023

Multiple sclerosis (MS) pathology features autoimmune-driven neuroinflammation, demyelination, and failed remyelination. Carnosine is a histidine-containing dipeptide (HCD) with pluripotent homeostatic properties that is able to improve outcomes in an animal MS model (EAE) when supplied exogenously. To uncover if endogenous carnosine is involved in, and protects against, MS-related neuroinflammation, demyelination or remyelination failure, we here studied the HCD-synthesizing enzyme carnosine synthase (CARNS1) in human MS lesions and two preclinical mouse MS models (EAE, cuprizone). We demonstrate that due to its presence in oligodendrocytes, CARNS1 expression is diminished in demyelinated MS lesions and mouse models mimicking demyelination/inflammation, but returns upon remyelination.Carns1-KO mice that are devoid of endogenous HCDs display exaggerated neuroinflammation and clinical symptoms during EAE, which could be partially rescued by exogenous carnosine treatment. Worsening of the disease appears to be driven by a central, not peripheral immune-modulatory, mechanism possibly linked to impaired clearance of the reactive carbonyl acrolein inCarns1-KO mice. In contrast, the presence of CARNS1 and endogenous HCDs does not protect against cuprizone-induced demyelination, and is not required for normal oligodendrocyte precursor cell differentiation and (re)myelin to occur. Exogenously administered carnosine is not effective in blunting demyelination or accelerating remyelination. In conclusion, we show that CARNS1 is diminished in demyelinated MS lesions, which may have detrimental effects on disease progression through weakening the endogenous protection against neuroinflammation.
Handedness and its association with education and spatial navigation assessed in over 400,000 participants across 41 countries
Authors: Fernandez-Velasco P. , Coutrot A. , Oloye H. , Wiener J.M. , Dalton R.C. , Hoelscher C. , Manley E. , Hornberger M. , Spiers H.J
Published: April 2023

There is an active debate concerning the association of handedness and spatial ability. Past studies used small sample sizes within a single country. Determining the effect of handedness on spatial ability requires a large, cross-cultural sample of participants, and a navigation task with real-world validity. Here, we overcome these challenges via the mobile app Sea Hero Quest. We analysed the navigation performance from 422,772 participants from 41 countries and found no reliable evidence for any difference in spatial ability between left- and right-handers across all countries. Using 749,037 participants from the larger sample, we replicate previous findings that age, gender, and country of residence have an impact on the prevalence of left-handedness, and found an effect of education on left-handedness prevalence in China, Indonesia, India, Taiwan, and Hong Kong. Our study clarifies the factors associated with spatial ability and outlines new ways in which cultural patterns influence handedness.

Statement of Relevance

What is the relation between handedness and navigation ability? Evidence so far has been mixed, and findings from small-scale and large-scale tasks seem to point in opposite directions. Part of the reason is that cultural and sociodemographic differences have a significant impact on both spatial ability and handedness. Tackling the question requires a large, cross-cultural sample of participants performing an ecologically valid navigation task. Here, we employ a mobile app, Sea Hero Quest, to test the navigation ability of a large number of participants across many different countries. What we find is that there is no reliable connection between handedness and navigation ability. Then, we use our data to explore the prevalence of left-handedness across countries, and find that age, gender, and country of residency all have an effect on the ratio of left-handedness. Moreover, we find an effect of education on left-handedness in China, Indonesia, India, Taiwan, and Hong Kong.
Sodium-mediated plateau potentials in an identified decisional neuron contribute to feeding-related motor pattern genesis inAplysia
Authors: Bédécarrats Alexis , Simmers John , Nargeot Romuald
Published: April 2023

Motivated behaviors such as feeding depend on the functional properties of decision neurons which provide the flexibility required for behavioral adaptation. Here, we analyzed the ionic basis of the endogenous membrane properties of an identified decision neuron (B63) that drive radula biting cycles underlying food-seeking behavior inAplysia. Each spontaneous bite cycle arises from the irregular triggering of a plateau-like potential and resultant bursting by rhythmic subthreshold oscillations in B63’s membrane potential. In isolated buccal ganglion preparations, and after synaptic isolation, the expression of B63’s plateau potentials persisted after removal of extracellular calcium, but was completely suppressed in a TTX-containing bath solution, thereby indicating the contribution of a transmembrane Na+influx. Potassium outward efflux through TEA- and calcium-sensitive channels was found to contribute to each plateau’s active termination. This intrinsic plateauing capability, in contrast to B63’s membrane potential oscillation, was blocked by theICANblocker flufenamic acid (FFA). Conversely, the SERCA blocker cyclopianozic acid (CPA), which abolished the neuron’s oscillation, did not prevent the expression of experimentally evoked-plateau potentials. These results therefore indicate that the dynamic properties of the decision neuron B63 rely on two distinct mechanisms involving different sub-populations of ionic conductances.

NEW & NOTEWORTHY

Here, we report an endogenous plateau property underlying bursting in a bilateral pair of buccal ganglion pacemaker neurons (B63) which trigger individual motor pattern cycles for food-seeking behavior in the marine molluskAplysia. The ionic mechanisms of this membrane bistability in B63 rely critically on voltage-dependent sodium inward currents. The expression of these plateau properties and the underlying endogenous oscillatory pacemaker drive can be dissociated pharmacologically, indicating that the two intrinsic properties depend on different sets of conductances. Our results thus shed new light on the mechanisms of spontaneous decision making inAplysia.
Inferring interactions from microbiome data
Authors: Zapién-Campos Román , Bansept Florence , Traulsen Arne
Published: April 2023

Parameter inference of high-dimensional data is challenging and microbiome time series data is no exception. Methods aimed at predicting from point estimates exist, but often even fail to recover the true parameters from simulated data. Computational methods to robustly infer and quantify the uncertainty in model parameters are needed. Here, we propose a computational workflow addressing such challenges – allowing us to compare mechanistic models and identify the values and the certainty of inferred parameters. This approach allows us to infer which kind of interactions occur in the microbial community. In contrast to point-estimate inference, the distribution for the parameters, our outcome, reflects their uncertainty. To achieve this, we consider as many equations for the statistical moments of the microbiome as parameters. Our inference workflow, which builds upon a mechanistic foundation of microscopic processes, can take into account that commonly metagenomic datasets only provide information on relative abundances and hosts’ ensembles. With our framework, we move from qualitative prediction to quantifying the likelihood of certain interaction types in microbiomes.
Differentiation of vaginal cells from epidermal cells using morphological and autofluorescence properties: Implications for sexual assault casework involving digital penetration
Authors: Ingram Sarah , DeCorte Arianna , Gentry Amanda , Philpott M. Katherine , Moldenhauer Taylor , Stadler Sonja , Steinberg Cory , Millman Jonathan , Ehrhardt Christopher J.
Published: April 2023

Analysis of DNA mixtures from sexual assault evidence is an ongoing challenge for DNA casework laboratories. There is a significant need for new techniques that can provide information as to the source of DNA, particularly for sexual assault samples that do not involve semen. The goal of this study was to develop a new biological signature system that provides additional probative value to samples comprised of mixtures of epidermal and vaginal cells, as may be observed in cases involving digital penetration. Signatures were based on morphological and autofluorescence properties of individual cells collected through Imaging Flow Cytometry (IFC). Comparisons to reference cell populations from vaginal tissue and epidermal cells collected from hands showed strong multivariate differences across >80 cellular measurements. These differences were used to build a predictive framework for classifying unknown cell populations as originating from epithelial cells associated with digital penetration or epidermal tissue. As part of the classification scheme, posterior probabilities of specific tissue group membership were calculated for each cell, along with multivariate similarity to that tissue type. We tested this approach on cell populations from reference tissue as well as mock casework samples involving digital penetration. Many more cells classifying as non-epidermal tissue were detected in digital penetration samples than control hand swabbings. Minimum interpretation thresholds were developed to minimize false positives; these thresholds were also effective when screening licked hands, indicating the potential utility of this method for a variety of biological mixture types and depositional events relevant to forensic casework. Results showed that samples collected subsequent to digital penetration possessed markedly higher numbers of cells classifying as vaginal tissue as well as higher posterior probabilities for vaginal tissue (≥ 0.90) compared to cell populations collected from hands without prior contact with vaginal tissue. Additionally, digital penetration cell populations may be resolved from saliva cell populations and other non-target tissue types.
Sox11 is enriched in myogenic progenitors but dispensable for development and regeneration of skeletal muscle
Authors: Oprescu Stephanie N. , Baumann Nick , Chen Xiyue , Sun Qiang , Zhao Yu , Yue Feng , Wang Huating , Kuang Shihuan
Published: April 2023

Transcription factors (TFs) play key roles in regulating the differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment ofSox11mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data,Sox11levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate thatSox11expression is reduced in aged MuSCs. Age-related decline ofSox11expression is associated with reduced chromatin contacts within the topologically associated domains. Unexpectedly, Myod1Cre-driven deletion ofSox11in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreERor Rosa26CreERdriven (MuSC-specific or global) deletion ofSox11in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remain to be elucidated.
Matrin3 mediates differentiation through stabilizing chromatin accessibility and chromatin loop-domain interactions, and YY1 mediated enhancer-promoter interactions
Authors: Liu Tianxin , Zhu Qian , Yan Kai , Bingham Trevor , Cha Hye Ji , Mehta Stuti , Schlaeger Thorsten M , Yuan Guo-Cheng , Orkin Stuart H
Published: April 2023

Although emerging evidence indicates that alterations in proteins within nuclear compartments elicit changes in chromosomal architecture and differentiation, the underlying mechanisms are not well understood. Here we investigate the direct role of the abundant nuclear complex protein Matrin3 (Matr3) in chromatin architecture and development in the context of myogenesis. Using an acute targeted protein degradation platform (dTAG-Matr3), we reveal the dynamics of development-related chromatin reorganization. Upon acute depletion of Matr3, gains in chromatin accessibility and MyoD binding were observed, prior to widespread loss in the steady-state Matr3-knockout. These initial changes correlated with gene expression changes later in development. High-throughput chromosome conformation capture (Hi-C) experiments revealed substantial chromatin loop rearrangements soon after Matr3 depletion. Notably, YY1 binding was detected in close proximity to enhancer and promoter regions, accompanied by the emergence of novel YY1-mediated enhancer-promoter loops, which occurred concurrently with changes in histone modifications and chromatin-level binding patterns. Overall, our results suggest that Matr3 mediates differentiation through stabilizing chromatin accessibility and chromatin loop-domain interactions, and highlight a conserved and direct role for Matr3 in maintenance of chromosomal architecture.
The bioactive dietary polyphenol preparation alleviates depression and anxiety-like behaviors by modulating the regional heterogeneity of microglia morphology
Authors: Yang Eun-Jeong , Frolinger Tal , Westfall Susan , Iqbal Umar Haris , Murrough James , Pasinetti Giulio M.
Published: April 2023

Scope

The goal of this study is to investigate the effects of a bioactive dietary polyphenol preparation (BDPP), which is made up of grape-derived polyphenols, on microglial responses, as well as the underlying molecular mechanisms in depression and anxiety-like behaviors.

Methods and results

We find that treatment with BDPP significantly decreased depression-like and anxiety-like behaviors induced by chronic stress in mice, while leaving their locomotor activity unaffected. We also find that BDPP treatment reversed microglia activation in the amygdala and hippocampal formation, regions of the brain involved in emotional regulation, from an amoeboid shape to ramified shape. Additionally, BDPP treatment modulates the release of pro-inflammatory cytokines such as interleukin-6 via high mobility box 1 protein and the receptor for advanced glycation end products (HMGB1-RAGE) signaling pathway in activated microglia induced by chronic stress.

Conclusion

Our findings suggest regional heterogeneity in microglial responses following chronic stress in subregions of the corticolimbic circuit. Specifically, activation of the immune-inflammatory HMGB1-RAGE pathway might provide a new avenue for therapeutic intervention in stress-induced anxiety- and depression-like behavior, using bioactive and bioavailable polyphenols.
Early microbial intervention reduces diarrhea while improves later milk production in newborn calves
Authors: Shen Yizhao , Li Yan , Wu Tingting , Dong Quanbin , Deng Qiufeng , Liu Lu , Guo Yanfei , Cao Yufeng , Li Qiufeng , Shi Jing , Zou Huayiyang , Jiao Yuwen , Ding Luoyang , Li Jianguo , Gao Yanxia , Hu Shixian , Wang Yifeng , Chen Lianmin
Published: April 2023

The rumen of neonatal calves is not well-developed and exhibits limited functionality. Therefore, the establishment of intestinal microbiota may play an instrumental role in their health and performance, but it has been rarely explored. Thus, we aim to explore the temporal colonization of the gut microbiome and the potential benefits of early microbial intervention in newborn calves. We followed up on the temporal dynamics of the gut microbiome and plasma metabolome in 36 newborn calves during the first two months of life and established their relationships with their health status and performance. We also evaluated whether microbiota transplantation (MT) could influence their phenotypes by modulating metabolism and its impact on later milk production performance.We showed that the composition and ecological interactions of the gut microbiome are likely to reach maturity one month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction ofBacteroidesspecies, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion, antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. The data from the study may help develop strategies to manipulate the gut microbiota during early life, which may be significantly relevant to the health and production of newborn calves.

HIGHLIGHTS

The gut microbial composition and ecological interaction in newborn calves reach maturity one month after birth

Temporal shifts in the gut microbiome of newborn calves are associated with phenotypic changes, including growth, digestion, and antioxidative capacity

Early microbial intervention in newborn calves reduces diarrhea while improving later milk production

The gut microbial impact on newborn calves is mediated by plasma metabolites
Rhytidome- and cork-type barks of holm oak, cork oak and their hybrids highlight processes leading to cork formation
Authors: Armendariz Iker , López de Heredia Unai , Soler Marçal , Puigdemont Adrià , Mercè Ruiz Maria , Jové Patricia , Soto Álvaro , Serra Olga , Figueras Mercè
Published: April 2023

The periderm is basic for land plants due to its protective role during radial growth, which is achieved by the polymers deposited in the cell walls. In most trees, like holm oak, the periderm is frequently replaced by subsequent internal periderms yielding a heterogeneous outer bark made of a mixture of periderms and phloem tissues, known as rhytidome. Exceptionally, cork oak forms a persistent or long-lived periderm which results in a homogeneous outer bark of thick phellem cell layers known as cork. Here we use the outer bark of cork oak, holm oak, and their natural hybrids’ to analyse the chemical composition, the anatomy and the transcriptome, and further understand the mechanisms underlying periderm development. The inclusion of hybrid samples showing rhytidome-type and cork-type barks is valuable to approach to cork and rhytidome development, allowing an accurate identification of candidate genes and processes. The present study underscores that biotic stress and cell death signalling are enhanced in rhytidome-type barks whereas lipid metabolism and cell cycle are enriched in cork-type barks. Development-related DEGs, showing the highest expression, highlight cell division, cell expansion, and cell differentiation as key processes leading to cork or rhytidome-type barks.
Optimizing expression of Nanobody®molecules in Pichia pastoris through co-expression of auxiliary proteins under methanol and methanol-free conditions
Authors: De Groeve Manu , Laukens Bram , Schotte Peter
Published: April 2023

Background

Ablynx NV, a subsidiary of Sanofi, has a long-standing focus on the development of Nanobody®molecules as biopharmaceuticals (Nanobody®is a registered trademark of Ablynx NV). Nanobody molecules are single variable domains, and they have been met with great success part due to their favorable expression properties in several microbial systems. Nevertheless, the search for the host of the future is an ongoing and challenging process.Komagataella phaffi(Pichia pastoris) is one of the most suitable organisms to produce Nanobody molecules. In addition, genetic engineering of Pichia is easy and an effective approach to improve titers.

Results

Here we report thatP. pastorisengineered to co-express genes encoding four auxiliary proteins (HAC1, KAR2, PDI and RPP0), leads to a marked improvement in the expression of Nanobody molecules using the AOX1 methanol induction system. Titer improvement is mainly attributed to HAC1, and its beneficial effect was also observed in a methanol-free expression system.

Conclusion

Our findings are based on over a thousand fed-batch fermentations and offer a valuable guide to produce Nanobody molecules inP. pastoris. The presented differences in expressability between types of Nanobody molecules will be helpful for researchers to select both the type of Nanobody molecule and Pichia strain and may stimulate further the development of a more ecological methanol-free expression platform.
Considerations on brain age predictions from repeatedly sampled data across time
Authors: Korbmacher Max , Wang Meng-Yun , Eikeland Rune , Buchert Ralph , Andreassen Ole A. , Espeseth Thomas , Leonardsen Esten , Westlye Lars T. , Maximov Ivan I. , Specht Karsten
Published: April 2023

Introduction

Brain age, the estimation of a person’s age from magnetic resonance imaging (MRI) parameters, has been used as a general indicator of health. The marker requires however further validation for application in clinical contexts. Here, we show how brain age predictions perform for for the same individual at various time points and validate our findings with age-matched healthy controls.

Methods

We used densly sampled T1-weighted MRI data from four individuals (from two datasets) to observe how brain age corresponds to age and is influenced by acquision and quality parameters. For validation, we used two cross-sectional datasets. Brain age was predicted by a pre-trained deep learning model.

Results

We find small within-subject correlations between age and brain age. We also find evidence for the influence of field strength on brain age which replicated in the cross-sectional validation data, and inconclusive effects of scan quality.

Conclusion

The absence of maturation effects for the age range in the presented sample, brain age model-bias (including training age distribution and field strength) and model error are potential reasons for small relationships between age and brain age in longitudinal data. Future brain age models should account for differences in field strength and intra-individual differences.
Spatiotemporal coordination of Rac1 and Cdc42 at the whole cell level during cell ruffling
Authors: Hladyshau Siarhei , Stoop Jorik P , Kamada Kosei , Nie Shuyi , Tsygankov Denis V
Published: April 2023

Rho-GTPases are central regulators within a complex signaling network that controls the cytoskeletal organization and cell movement. This network includes multiple GTPases, such as the most studied Rac1, Cdc42, and RhoA, and their numerous effectors that provide mutual regulation and feedback loops. Here we investigate the temporal and spatial relationship between Rac1 and Cdc42 during membrane ruffling using a simulation model which couples GTPase signaling with cell morphodynamics to capture the GTPase behavior observed with FRET-based biosensors. We show that membrane velocity is regulated by the kinetic rate of GTPase activation rather than the concentration of active GTPase. Our model captures both uniform and polarized ruffling. We also show that cell-type specific time delays between Rac1 and Cdc42 activation can be reproduced with a single signaling motif, in which the delay is controlled by feedback from Cdc42 to Rac1. The resolution of our simulation output matches those of the time-lapsed recordings of cell dynamics and GTPase activity. This approach allows us to validate simulation results with quantitative precision using the same pipeline for the analysis of simulated and experimental data.
A multi-actor ICT platform for increasing sustainability and resilience of small-scale farmers after pandemic crisis
Authors: Cimino Antonio , Longo Francesco , Solina Vittorio , Verteramo Saverino
Published: April 2023

Purpose

This paper proposes an Information and Communication Technology (ICT) platform to increase the sustainability and resilience of smallholders to face supply chain disruptions in the event of COVID-like crises. The platform facilitates interactions between smallholders and buyers, workers and freight transport companies in agri-food ecosystems. Furthermore, this research work presents the implementation of the freight transport companies’ platform module.

Design/methodology/approach

The research work begins with a literature review aiming at analyzing current available ICT solutions supporting smallholders and other actors in the agri-food supply chain. This analysis identifies the research gaps which have to be filled by the platform. Then, the authors proceed with the analysis of the operational scenarios of each platform actor by interacting with experts and operators working in the agri-food sector. The results of such analysis resulted in a comprehensive, unambiguous and consistent set of specification being used to define the platform structure and modules architecture. The platform modules have been developed by using the web-application framework Laravel.

Findings

Preliminary tests show that the proposed platform is usable and promises to improve the resilience and economic, social and environmental sustainability of agri-food supply chains, with a focus on smallholders.

Originality/value

The research work allows players in the agri-food supply chain and in particular small local producers to react and mitigate the impact of COVID-like crises through development of a platform in which smallholders, citizens (buyers and workers) and freight transport companies are simultaneously present.
The mediating role of workplace spirituality between personal attributes and job performances of Indian bus drivers
Authors: Jayakumar V. , Vinodkumar M.N.
Published: April 2023

Purpose

Transport industry is one of the leading accident causing industries all around the world. Personal attributes like educational qualification, work experience, marital status, consumption of alcohol, hours of work of bus drivers are known to influence such accidents. In the present study, the mediating effects of Workplace spirituality (WS) among bus drivers between the personal attributes and job performance variables like self-reported accidents, punishments and appraisals are carried out.

Design/methodology/approach

A mediation analysis of WS between personal attributes and job performances of bus drivers is conducted in the present study. Since there is scarcity of studies measuring the effects of WS of bus drivers, new scale to measure WS was developed. The study was carried out in the government-owned road transport corporation in the state of Kerala, India. Responses were obtained from 617 male drivers.

Findings

Using exploratory factor analysis, four factors were identified, namely Meaningful work, Sense of Community, Mindfulness and Compassion. Confirmatory factory analysis provided good fit. The intercorrelations of personal attributes of drivers (independent variables) between WS factors (mediating variables) and job performance variables (dependent variables) were found out. Mediation analysis showed complete mediation of WS factors between marital status, alcohol consumption, hours of work and job performances like number of self-reported accidents, punishments and appraisals. The WS levels of drivers decrease significantly as working hours per goes beyond the legally allowed working hours.

Originality/value

Psychological attributes like Mindfulness, Sense of community, compassion etc. which are collectively known as WS influence the job performances of employees in other industries. Yet it is not studied in the transport industry. Hence, in the present study, the levels of WS are studied among bus drivers of government-owned road transport corporation in the State of Kerala, India.
Crisis as method: Critical events and moral breakdowns
Authors: Cabot Heath
Published: April 2023

This article calls for a deeper consideration of crisis as a method, as spearheaded by anthropologists trained in the Manchester School, including Max Gluckman, who followed extended case studies to track ‘crisis over time’. This approach examines how certain occurrences trigger reflection and deliberation beyond the event and activate critique of interlocutors and anthropologists, reinserting questions of ethics and morality. I argue that crisis as a method facilitates a move away from ‘crisis‐chasing’ apparent in anthropology over the past decade, which labels situations as ‘urgent’ while omitting constitutive aspects of social structure. Crisis as a method entails paying attention to the structures that name or call crisis into being and a critical perspective on what constitutes a crisis or noteworthy ‘event’.
Spatiotemporal patterns of research on Southern Hemisphere amphidromous galaxiids: A semi–quantitative review
Authors: Lee Finnbar , Boddy Nixie C. , Bloxham Matthew , McIntosh Angus R. , Perry George L. W. , Simon Kevin S.
Published: April 2023

Amphidromy is a distinctive life‐history strategy of some fish species that involves spawning in fresh or brackish water followed by dispersal to sea by newly hatched larvae, where they develop for a short period. Individuals then return to freshwater as juveniles, where they feed and grow, before maturing and spawning. Six amphidromous species from the Southern Hemisphere genus Galaxias (G. truttaceus, G. fasciatus, G. argenteus, G. postvectis, G. brevipinnis, G. maculatus) are recreationally, culturally, and economically important as the juveniles are harvested. Due to ongoing population declines and a lack of critical demographic information, there is growing concern about the management of the species. Here, we used semi‐quantitative review, culturomics, and bibliometric tools to analyse peer‐reviewed research conducted on the six amphidromous species of Galaxias to: (i) understand how spatiotemporal patterns of research have shifted over the last five decades, and (ii) identify critical research gaps. Forty percent of studies (n = 295) covered a spatial extent of 10 km or less and 87% of studies lasted less than 2 years – studies were largely small and short relative to the species' ranges and their longevity. Additionally, we found important research gaps; for example, studies on the effects of climate change and the associated effects of disturbance, and the marine phase are scarce in the peer‐reviewed literature. Finally, we suggest that quantitative models have been underutilized as tools for studying amphidromous galaxiids and should be embraced to answer questions not readily addressed with field and laboratory‐based techniques. If these species are to be effectively managed, their population dynamics across spatiotemporal scales must be understood and critical and long‐standing gaps in research knowledge addressed.