bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular basis of integrin-dependent cell adhesion
Authors: Humphries Martin J , Liddington Robert C
Published: November 2023

The integrins are a family of heterodimeric (α β) plasma membrane proteins that bind the extracellular matrix or counter-receptors on other cells (1). They transduce bidirectional signals across the plasma membrane that are critical to many biological processes, including embryonic cell migration, wound healing, and the immune response. In pathogenic states they play an essential role in tumour metastasis and angiogenesis. The adhesiveness of integrins’ extracellular domains is allosterically controlled by binding events in their cytoplasmic domains that trigger conformational changes across the plasma membrane (‘inside-out’ signalling). Under some conditions it is ligand binding to the extracellular domains that triggers an intracellular signal (‘outside-in’ signalling). There are two mechanisms by which integrins could change the adhesiveness of cells, which are not necessarily exclusive. ‘Affinity’ changes caused by conformational changes in individual integrin molecules are believed to be responsible for both the initial rapid and reversible change in the affinity of platelets for damaged blood vessels and of leucocytes for sites of inflammation (2). ‘Avidity’ changes brought about by the synergistic effect of multiple clustered integrins on the cell surface binding to clustered or polyvalent ligands are thought to play a role in the stable attachment of cells to the extracellular matrix (ECM) (3).
The cell cycle
Authors: Tyers Mike , Jorgensen Paul
Published: November 2023

The accurate replication and segregation of the genome during cell division is orchestrated by the cyclin-dependent protein kinases (CDKs) and their attendant regulatory partners, the cyclins and CDK inhibitors. At its most fundamental level, the cell division machinery is programmed by a state of low CDK activity in GI phase and a state of high CDK activity in S, G2 and M phase. These two states dictate the once and only once replication and segregation of the genome per division cycle. Thus, low CDK activity triggers exit from mitosis and the establishment of competent origins of DNA replication, whereas high CDK activity activates firing of prereplicative origins, prevents the refiring of spent origins and catalyses entry into mitosis. The alternation between the two CDK states is controlled by a switch that is flipped once in each direction per cell cycle. In late G1 phase, CDK activity is switched on while in late mitosis it is switched off. This switch is constructed from three major elements: CDK-dependent phosphorylation, cell cycle-regulated waves of transcription, and ubiquitin-dependent proteolysis of key regulatory proteins. In this chapter, we describe the mechanisms that generate the fundamental oscillation in CDK activity that lies at the heart of the cell cycle in the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe.
The structure of yeast centromeres and telomeres and the role of silent heterochromatin
Authors: Pidoux Alison L , Allshire Robin C
Published: November 2023

Genome stability and accurate chromosome segregation are of paramount importance to the cell and to the organism. The consequences of mistakes in mitosis and meiosis are severe indeed. In unicellular eukaryotes, aneuploidy is often deleterious or even fatal. For complex eukaryotes, chromosome gain or loss events are a leading cause of genetic diseases, miscarriage, and birth defects, and contribute to the progression of cancer. Chromosome rearrangements and fusions resulting from free DNA ends (e.g. those lacking telomeres) may have profoundly deleterious effects. To ensure their structural integrity and successful transmission, chromosomes must have origin(s) of replication, a single functional centromere and, if linear, telomeres.

The centromere was originally defined cytologically on mammalian chromosomes as the site of the primary constriction. Together with its associated proteinaceous kinetochore, this region of DNA is responsible for chromosome attachment to spindle microtubules and chromosome segregation at cell division (1). Centromcres perform very precise functions; during the S phase of the cell cycle, chromosomes are replicated, but the two chromatids must remain associated at their centromere until mitosis. At the onset of mitosis, sister kinetochores must specifically bind to microtubules emanating from the two opposite poles of the spindle. When all chromosomes are correctly attached and oriented on the metaphase plate, the sister chromatids part company and move to the spindle poles in anaphase, led by their kinetochores. In meiosis the situation is more complex.
Cell labelling and transplantation techniques
Authors: Kane Donald A , Kishimoto Yasuyuki
Published: November 2023

What with their genetics, zebrafish have become the Drosophila of the vertebrates. But these little fish have many other advantages. As the developmental biologists of the mid-twentieth century knew (1), zebrafish are superb for observational studies of development. Their eggs are fertilized externally, so that it is a simple matter to have the embryos on a compound microscope a few moments after fertilization. There, the transparent embryo reveals the early cell cleavages of the blastula, the cell movements of the gastrula, or, later, the forming internal organs of the larva. In situ hybridization and antibody reactions are done as whole mounts, for sectioning can be done later, if at all. And if lineage tracer is injected into cells, as we describe in this chapter, the cells can be recorded for days, and sometimes weeks, afterwards. The technique of moving about pieces of tissue from embryo to embryo has been an essential part of developmental biology for nearly a century. By placing developing cells into ectopic positions, we test the potential of the transplanted cells to develop into fates appropriate for the new position. These techniques, described in this chapter, are essential for connecting the developmental biology of the zebrafish to that of more traditional experimental vertebrates, such as Xenopus and chick, and are also necessary for the analysis of gene action in the zebrafish mutants.
Speculations on the origin and evolution of editing
Authors: Gray Michael W
Published: November 2023

The discovery of RNA editing quickly prompted three evolutionary-type questions: how did it evolve, why and when? In many cases, RNA editing appears to fix a problem in genetic information transfer. In mRNA, coding regions are brought into frame (1) or even created de novo (2, 3), codons are changed so they specify phylo genetically conserved amino acids (4, 5) and initiation and termination codons are formed (4, 6–14). The result is a translatable mRNA that codes for a functional protein, one that could not have been made in the absence of editing. In non-coding RNAs (rRNA and tRNA), missing primary and/or secondary structural motifs are restored, again creating a functional RNA from a non-functional transcript (15–17). In certain instances, intron sequences must be edited to produce a splicing-competent structure (18). Because of these characteristics, RNA editing systems have often been regarded as having an RNA repair function, with this role serving as their evolutionary raison d’être.
Risk Assessments For The Use Of Radioisotopes In Biology
Authors: Ballance Peter E
Published: November 2023

Ever since the early 1950s when radioisotopes began to be used extensively in experimental biology, research group leaders, supervisors and individual researchers instinctively asked themselves what were the hazards from the radioactive materials to be used, what were the risks to health and how these risks should be minimized. In the process of selecting radioisotopes for particular experiments, research workers needed to obtain detailed information on the way radioisotopes decayed. In order to use radioisotopes as tracers for specific elements or compounds in biological systems, they needed to know whether charged particles or electromagnetic radiation (or both) were emitted, and hence how to determine the best choice of radiation detection equipment to be used. From the physical data available they were able to gain some insight into the likely hazards which would be associated with the presence of the radioactive elements. With the well documented knowledge of the effects of ionizing radiation on living organisms, particularly the effects of atomic weapons, they instinctively sought to assess the risks to their health and, in turn, to take steps to minimize these risks.
Radioisotope Detection Using X-Ray Film
Authors: Laskey Ron A
Published: November 2023

During the last three decades gel electrophoresis has steadily replaced other methods for analytical fractionation of macromolecules. This chapter describes and discusses methods of detecting radioisotopes within flat samples such as accylamide or agarose gels, nitrocellulose filters, thin layer chromatography plates and paper chromatograms. For all of these samples X-ray film provides a convenient non-destructive means of isotope detection which combines high sensitivity with high resolution. Alternative storage phosphor technology is described in Chapter 5. Autoradiography of microscopy slides is described in Chapter 9.
In vitro Labelling Of Nucleic Acids And Proteins
Authors: Cunningham M W , Patel A , Simmonds A C , Williams D
Published: November 2023

Radioactive tracers are uniquely suited for the labelling of biological molecules because their presence generally has no effect on the properties of those molecules. Indeed, most of the radioisotopes used can be incorporated into biomolecules in place of the equivalent non-radioactive element. This is particularly important when the biomolecule is itself being used as an enzyme substrate since enzymes tend to display a strong selectivity for their specific substrates.
Summary Of Legislation In Radiological Protection In The UK
Authors: Prime David , Frith Barry
Published: November 2023

The use of equipment or materials that emit radiations is governed by two pieces of legislation-the Radioactive Substances Act (1993) and the Ionising Radiations Regulations (1999). This legislation imposes a system of radiological protection that is almost the same in all premises using radioactive materials or radiation-emitting equipment. This system will be outlined in two sections dealing with the respective items of legislation.
Probing G protein-coupled receptors by fluorescence spectroscopy
Authors: Turcatti Gerardo
Published: November 2023

The broad development of approaches based on fluorescence detection in receptor research in recent years can be seen as a consequence of two main scientific advances. First, is the development and optimization of systems for the overexpression ofreceptors (1) that started early in the 1990s. Classic fluorescent techniques, that were not sensitive enough to detect receptors from natural sources or poorly expressed recombinant receptors, became available for this purpose with the important advantage of several years of experimentation behind them. Secondly, are the methodological and instrumental improvements in the sensitivity of fluorescence measurements that can now detect single molecules (for a review see ref. 2).
From receptor to endogenous ligand
Authors: Nothacker Hans-Peter , Reinscheid Rainer K , Civelli Olivier
Published: November 2023

Homology screening and advances in the human genome project have spawned an explosion in the field ofG protein-coupled receptors (GPCRs) resulting in the discovery of hundreds of new ones. A large number of these bind unknown natural ligands and are called ‘orphan’ GPCRs. The major challenge lies in the discovery of their functions, defining their physiological roles, and possibly their therapeutic potentials. The key to this daunting task lies in the identification of the natural endogenous ligand(s) that bind to and activate the orphan GPCRs. These ligands can then be used in behavioural assays to attempt to define the functional role of the orphan receptor systems. They can also be used to develop specific agonists and antagonists ultimately to provide therapeutic drugs.
Monitoring nuclear receptor function
Authors: Nunez B Scott , Vedeckis Wayne V
Published: November 2023

The glucocorticoid receptor (GR), one of the first nuclear receptors to be characterized and to have its gene cloned, serves to illustrate the complexity of nuclear receptor function. The expression of the GR gene is regulated by at least three different promoters and the resulting mRNAs can be differentially spliced into several transcriptional variants (1-3). Following the translation of these transcripts into protein, the activity and/or subcellular distribution of the GR protein may be modified by post-translational modifications such as phosphorylation (4). In the absence of ligand, the GR is found primarily in the cytoplasm associated with protein chaperones, such as heat shock protein 90 (HSP 90), which act to maintain the receptor in an inactive state (5). Other proteins, called co-activators and co-repressors, bind to and modulate the transcriptional activity of nuclear receptors (6). The GR is activated by binding glucocorticoid (GC): it is then translocated into the nucleus where it can alter gene transcription through two avenues. The classical mode of action is for activated GR to alter transcription directly by binding a glucocorticoid responsive element (GRE), a negative glucocorticoid responsive element (NGRE), or a composite GRE. The GR can also alter transcription directly without binding DNA by interacting with other transcription factors that bind DNA. The second avenue of GR action is via transcriptional interference, whereby the activity of a transcription factor is diminished by an interaction with the GR (7).
Sequence databases and analysis sites
Authors: Apweiler Rolf , Lopez Rodrigo
Published: November 2023

EMBL Outstation, The European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, UK. Recent years have seen an explosive growth in biological data, which is often not published anymore in a conventional sense, but deposited in a database. Sequence data from mega-sequencing projects may not even be linked to a conventional publication. This trend and the need for computational analyses of the data make databases and database search tools essential for biological research.
Agricultural biotechnology
Authors: Carollo Victoria
Published: November 2023

It is widely agreed that humans made the transition from a nomadic huntergatherer lifestyle to one dependant largely on agriculture about 10,000 years ago in the Pre-Pottery Neolithic Near East. Archeological evidence of the Neolithic founder crops (einkorn wheat, emmer wheat, barley, lentil, pea, bitter vetch, chickpea, and flax) has been traced to a small area within the ‘Fertile Crescent’ near the upper Tigris and Euphrates rivers in what today is southeast Turkey and northern Syria (1).
Internet collaboration
Authors: Atherton David , Lau Chin Hoon , Kondu Pinar , Gore-Langton Robert E , Leifer Zev
Published: November 2023

This chapter surveys the types of technologies, applications, and organizational approaches that best support the needs of scientific collaboration. Although briefly covering the foundations of internet communications technologies, such as e-mail and newsgroups, emphasis has been placed on solutions to support real-time interactions and shared tools since we believe these provide the greatest opportunities for meaningful collaboration. Some of these tools also provide the greatest technological challenges, but the rewards in terms of creativity and efficiency are often worth the effort.
A Longitudinal Study of Gaming Patterns During the First 11 Months of the COVID-19 Pandemic
Authors: Ritchie Emma V. , Rapinda Karli , Wardell Jeffrey D. , Kim Hyoun S. , Keough Matthew T.
Published: November 2023

Objectives:

The objective of this study was to longitudinally study engagement in video gaming throughout the first 11 months of the COVID-19 pandemic using latent growth curve modeling.

Methods:

A total of 332 Canadian adults (M
age=33.79, 60.8% men) who played video games were recruited from the crowdsourcing site Prolific. Participants responded to 4 waves of surveys (spaced 3 mo apart) from April 2020 to March 2021. The main outcome of interest was time spent gaming, measured in hours spent gaming in the past 30 days before each assessment wave.

Results:

Latent growth curve modelling showed that participants reported high initial levels of gaming, but progressively declined in gaming activity across the subsequent waves. Being male, living with others, experiencing a decrease in income because of COVID-19, endorsement of disordered gaming symptoms, game preference, and solitary gaming were significant predictors of increased gaming at the outset of the pandemic. However, only age was related to longer-term declines in gaming during the pandemic, such that older participants’ gaming decreased at a more accelerated rate.

Conclusions:

This study suggests that gaming declined over the course of the pandemic and was not a problematic behaviour on average among a community sample of Canadian adults during the COVID-19 pandemic.

Objectifs:

L’objectif de cette étude était d'étudier longitudinalement l’engagement dans les jeux vidéo au cours des onze premiers mois de la pandémie de COVID-19 en utilisant la modélisation de la courbe de croissance latente.

Méthodes:

Au total, 332 adultes canadiens (âge=33,79, 60,8% d’hommes) jouant à des jeux vidéo ont été recrutés sur le site de recrutement Prolific. Les participants ont répondu à quatre vagues d’enquêtes (espacées de 3 mois) d’avril 2020 à mars 2021. Le principal résultat d’intérêt était le temps passé à jouer, mesuré en heures passées à jouer au cours des 30 derniers jours précédant chaque vague d'évaluation.

Résultats:

La modélisation de la courbe de croissance latente a montré que les participants ont signalé des niveaux initiaux élevés de jeu, mais ont progressivement diminué leur activité de jeu au cours des vagues suivantes. Le fait d'être un homme, de vivre avec d’autres personnes, de subir une baisse de revenu en raison du COVID-19, d’endosser des symptômes de troubles du jeu, les préférences de jeux et de jouer en solitaire étaient des facteurs prédictifs significatifs d’une augmentation de l’activité de jeu au début de la pandémie. Cependant, seul l'âge était lié à une diminution à plus long terme du jeu pendant la pandémie, de sorte que le temps de jeu des participants plus âgés diminuait à un rythme plus rapide.

Conclusions:

Cette étude, prise parmi un échantillon communautaire d’adultes canadiens pendant la pandémie de COVID-19, suggère qu’en moyenne, le jeu a diminué au cours de la pandémie et n’a pas été un comportement problématique.
Chronic pharmacological activation of SERCA with CDN1163 affects spatial cognitive flexibility but not attention and impulsivity in mice
Authors: Klocke Benjamin , Moore Carter , Ott Hayden , Pitychoutis Pothitos M.
Published: November 2023

Intracellular calcium (Ca2+) homeostasis is critical for many neural processes, including learning, memory and synaptic plasticity. The sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) is among the key regulators that preserve Ca2+ homeostasis in neurons. SERCAs comprise a set of ubiquitously expressed Ca2+ pumps that primarily function to sequester cytosolic Ca2+ into endoplasmic reticular stores. As SERCA has been implicated in the neurobiology of several neuropsychiatric and neurodegenerative diseases, pharmacological harnessing of its function is critical in understanding SERCA’s role in brain physiology and pathophysiology. In the current study, we employed the Morris water maze and 5-choice serial reaction time task (5-CSRTT) to investigate the effects of chronic pharmacological activation of SERCA, using the small allosteric SERCA activator CDN1163, on spatial learning and memory, and executive functioning in naive C57BL/6J mice. Our data show that chronic pharmacological SERCA activation with CDN1163 (20 mg/kg) selectively impairs spatial cognitive flexibility and reversal learning in the Morris water maze while leaving executive functions such as attention and impulsivity intact. Present findings contribute to the growing field of the role of SERCA function in the brain and behavior and expand current knowledge on the use of the small allosteric activator CDN1163 as an investigational tool to study the role of SERCA in regulating neurobehavioral processes and as a potential therapeutic candidate for debilitating brain disorders.
Cardioprotective Action of a Novel Synthetic 19,20-EDP Analog Is Sirt Dependent
Authors: Kranrod Joshua W. , Darwesh Ahmed M. , Bassiouni Wesam , Huang Andy , Fang Liye , Korodimas Jacob V. , Adebesin Adeniyi Michael , Munnuri Sailu , Falck John R. , Seubert John M.
Published: November 2023

Mounting evidence suggests that cytochrome P450 epoxygenase–derived metabolites of docosahexaenoic acid, called epoxydocosapentaenoic acids (EDPs), limit mitochondrial damage after cardiac injury. In particular, the 19,20-EDP regioisomer has demonstrated potent cardioprotective action. Thus, we investigated our novel synthetic 19,20-EDP analog SA-22 for protection against cardiac ischemia–reperfusion (IR) injury. Isolated C57BL/6J mouse hearts were perfused through Langendorff apparatus for 20 minutes to obtain baseline function, followed by 30 minutes of global ischemia. Hearts were then treated with vehicle, 19,20-EDP, SA-22, or SA-22 with the pan-sirtuin inhibitor nicotinamide or the SIRT3-selective inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) at the start of 40 minutes reperfusion (N = 5–8). We assessed IR injury–induced changes in recovery of myocardial function, using left ventricular developed pressure and systolic and diastolic pressure change. Tissues were assessed for electron transport chain function, SIRT1 and SIRT3, optic atrophy type 1, and caspase-1. We also used H9c2 cells in an in vitro model of hypoxia/reoxygenation injury (N = 3–6). Hearts perfused with SA-22 had significantly improved postischemic left ventricular developed pressure, systolic and diastolic recovery (64% of baseline), compared with vehicle control (15% of baseline). In addition, treatment with SA-22 led to better catalytic function observed in electron transport chain and SIRT enzymes. The protective action of SA-22 resulted in reduced activation of pyroptosis in both hearts and cells after injury. Interestingly, although nicotinamide cotreatment worsened functional outcomes, cell survival, and attenuated sirtuin activity, it failed to completely attenuate SA-22–induced protection against pyroptosis, possibly indicating EDPs exert cytoprotection through pleiotropic mechanisms. In short, these data demonstrate the potential of our novel synthetic 19,20-EDP analog, SA-22, against IR/hypoxia-reoxygenation injury and justify further development of therapeutic agents based on 19,20-EDP.
Affinity purification-mass spectrometry and single fiber physiology/proteomics reveals mechanistic insights of C18ORF25
Authors: Ng Yaan-Kit , Blazev Ronnie , McNamara James W. , Dutt Mriga , Molendijk Jeffrey , Porrello Enzo R. , Elliott David A. , Parker Benjamin L.
Published: November 2023

C18ORF25 was recently shown to be phosphorylated at S67 by AMP-activated protein kinase (AMPK) in skeletal muscle following acute exercise in humans. Phosphorylation was shown to improveex vivoskeletal muscle contractile function in mice but our understanding of the molecular mechanisms is incomplete. Here, we profiled the interactome of C18ORF25 in mouse myotubes using affinity purification coupled to mass spectrometry. This analysis included an investigation of AMPK-dependent and S67-dependent protein:protein interactions. Several nucleocytoplasmic and contractile-associated proteins were identified, and revealed a subset of GTPases that associate with C18ORF25 in an AMPK- and S67 phosphorylation-dependent manner. We confirmed that C18ORF25 is localised to the nucleus and the contractile apparatus in skeletal muscle. Mice lackingC18Orf25display defects in calcium handling specifically in fast-twitch muscle fibers. To investigate these mechanisms, we developed an integrated single fiber physiology and single fiber proteomic platform. The approach enabled detailed assessment of various steps in the excitation-contraction (EC) pathway including SR calcium handling and force generation followed by paired single fiber proteomic analysis. This enabled us to identify >700 protein:phenotype associations and 36 fiber-type specific differences following loss ofC18Orf25. Taken together, our data provide unique insights into the function of C18ORF25 and its role in skeletal muscle physiology.
Moving together – Benefits of a 12-week online dance training intervention on static and dynamic postural stability and gait speed in older adults – a pre-post study
Authors: Hansen Rasmus Kopp , Jochum Elizabeth , Egholm Ditte , Villumsen Morten , Hirata Rogerio Pessoto
Published: November 2023

Background

Physical inactivity negatively affects gait performance and postural stability in older adults, which results in a higher risk of fall accidents. Previous research has shown that in-person dance training improves various aspects of balance and lower extremity function, however, the potential benefits of dance training delivered online on variables used for fall risk stratification in older adults have yet to be studied. We aimed to explore the benefits of a 12-week online dance training intervention on static and dynamic postural stability and gait speed in older adults.

Methods

Forty-five older adults were included. The 12-week dance training intervention consisted of two weekly 60-min classes in improvisation and salsa delivered online through Zoom video calls. Static and dynamic postural stability was assessed using the center of pressure (CoP) area and velocity (force platform), and the Mini Balance Evaluation Systems Test (Mini-BESTest), respectively. 10-m gait speed was measured using photo gates. Before and after comparisons were performed using paired sample t-tests.

Results

Thirty-two older adults completed the study. There were no significant changes for static postural stability assessed by CoP area or velocity (P ≥ 0.218). The Mini-BESTest total score was significantly improved at post-intervention (23.88 ± 3.01) compared to baseline (22.56 ± 1.41, P = 0.007). 10-m gait speed was significantly faster at post-intervention (1.68 ± 0.25 m/s) compared to baseline (1.57 ± 0.22 m/s, P < 0.001).

Discussion

These results indicate that online dance training has limited effect on static postural stability but may be beneficial for gait speed and in particular dynamic postural control among older adults. While the absolute increase in gait speed observed in the present study suggests limited clinical relevance, the improvement in Mini-BESTest score was above the minimal clinically important difference, which suggests a clinically relevant enhancement of dynamic postural control.
The Risk factors for fear of falling in chronic stroke patients: a systematic review and meta-analysis
Authors: Kong Yun , Zhong Kelong , An Xuemei
Published: November 2023

Background

The incidence rate of fear of falling in chronic stroke is high, which seriously affects the quality of life and rehabilitation effect of patients. Early identification of its risk factors will help clinical screening of high-risk patients and prevent their further development. There is currently no systematic evaluation of risk factors for fear of falling falls in chronic stroke.

Objective

We systematically reviewed the literature on risk factors for fear of fall in chronic patients with stroke.

Method

We systematically searched PubMed, Embase,cochrane,Web of Science and the China National Knowledge Infrastructure(CNKI),the china biomedical literature database(CBM),the China Science and Technology Periodicals Database(VIP),Wangfang data for relevant literature until May 2023.Review Manager V.5.3 merged the OR value and 95% CI of the potential risk factors.A random/fixed-effect meta-analysis was used to pool risk factors from individual studies.Cochran’s Q and the I2tests were used to assess heterogeneity between the studies.

Results

A total of 6 studies were included for the final analysis, with 965 chronic stroke patients. The risk factors for fear of falling in chronic patients with stroke were impaired balance ability (OR=3.05; 95% CI 1.60 to 5.80), history of falls (OR=2.12; 95% CI 1.40 to 3.20) and anxiety (OR=2.29; 95% CI 1.43 to 3.67), depression (OR=1.80; 95% CI 1.22 to 2.67), poor lower limb motor function (OR=1.14; 95% CI 1.00 to 1.29),physically inactiveness (OR=2.04; 95% CI 1.01 to 4.12). Married (OR=0.61; 95% CI: 0.435-0.875) is a protective factor.

Conclusion

Our study shows that impaired balance ability, history of falls might be a greater risk for fear of falling. Future studies are recommended to determine other risk factors specific to patients with chronic stroke.
Association between gut microbiome composition and symptom self-report in trauma exposed OEF/OIF/OND Veterans
Authors: Li Y. Irina , Pagulayan Kathleen , Rau Holly , Hendrickson Rebecca , Schindler Abigail G.
Published: November 2023

Objective

Iraq and Afghanistan war-era (OEF/OIF/OND) Veterans are at elevated risk for physical injuries and psychiatric illnesses, in particular comorbid mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and chronic pain. The gut microbiome has been implicated in modulation of critical processes such as digestion, immune system functioning, and stress responsivity, and may be an important factor in understanding physical and mental health outcomes following deployment and trauma exposure, yet minimal research to date has sought to characterize gut microbiome composition in this population.

Methods

26 male OEF/OIF/OND Veterans aged 18 to 65 who previously completed a VA Comprehensive TBI Evaluation were enrolled in this study. Participants completed self-report measures of PTSD symptom severity, pain intensity and interference, fatigue, cognitive symptoms, substance use, and sleep quality. Participants submitted fecal samples, and metagenomic sequencing was used to calculate alpha- and beta-diversity and taxonomic microbial composition. Associations between microbiome data and clinical variables was then examined.

Results

Alpha and beta diversity measures were not significantly correlated with clinical outcomes. Fatigue, post-concussive symptoms, executive function symptoms, and cannabis use were associated with differences in gut microbial composition, specifically Verrucomicrobiota.

Conclusion

This exploratory study demonstrated that altered gut microbiome composition is associated with psychiatric and cognitive symptoms in OEF/OIF/OND Veterans and highlights a potential new therapeutic target of interest. Future research is needed to examine whether probiotic treatment is effective for reducing symptoms common in this clinical population.
Telomeric repeat evolution in the phylum Nematoda revealed by high-quality genome assemblies and subtelomere structures
Authors: Lim Jiseon , Kim Wonjoo , Kim Jun , Lee Junho
Published: November 2023

Telomeres are composed of tandem arrays of telomeric-repeat motifs (TRMs) and telomere-binding proteins (TBPs), which are responsible for ensuring end-protection and end-replication of chromosomes. TRMs are highly conserved owing to the sequence specificity of TBPs, although significant alterations in TRM have been observed in several taxa, except Nematoda. We used public whole-genome sequencing data sets to analyze putative TRMs of 100 nematode species and determined that three distinct branches included specific novel TRMs, suggesting that evolutionary alterations in TRMs occurred in Nematoda. We focused on one of the three branches, the Panagrolaimidae family, and performed a de novo assembly of four high-quality draft genomes of the canonical (TTAGGC) and novel TRM (TTAGAC) isolates; the latter genomes revealed densely clustered arrays of the novel TRM. We then comprehensively analyzed the subtelomeric regions of the genomes to infer how the novel TRM evolved. We identified DNA damage–repair signatures in subtelomeric sequences that were representative of consequences of telomere maintenance mechanisms by alternative lengthening of telomeres. We propose a hypothetical scenario in which TTAGAC-containing units are clustered in subtelomeric regions and pre-existing TBPs capable of binding both canonical and novel TRMs aided the evolution of the novel TRM in the Panagrolaimidae family.
Business unit controllers' credibility and the hardening of local forecasts
Authors: Wiegmann Leona , Petrikowski Lukas , Goretzki Lukas
Published: November 2023

Focusing on multidivisional companies, this paper analyzes the hardening of local forecasts at the intersection of business units (BUs) and the corporate finance function. It investigates how BU controllers, accountable to both local management and the corporate finance function, seek to establish themselves as competent and trustworthy forecasters vis‐à‐vis their functional superiors. Drawing on Goffman's dramaturgical sociology, we demonstrate how these encounters constitute episodes in a multiperiod hardening game feeding into the management of forecast quality and anticipatory control. We illustrate how expressive performances of their competence and trustworthiness are vital for BU controllers to manage vertical information flows between the local and the corporate level and for aligning corresponding interests. Convincing performances can reinforce BU controllers' status as stewards of the forecasting process and help to maintain a “truce” between the local and the corporate level, assuring corporate controllers that the unit's future is under control.
Cytologic evaluation of upper urinary tract specimens: An institutional retrospective study using The Paris System for Reporting Urine Cytology second edition with histopathologic follow‐up
Authors: Khajir Ghazal , Sun Tong , Wang He , Sprenkle Preston C. , Adeniran Adebowale J. , Cai Guoping , Levi Angelique W.
Published: November 2023

Objective

Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow‐up.

Methods

An institutional database was reviewed for the UUT biopsy/resection histopathologic specimens, and we included 52 UUT cytology specimens pertinent to these cases in the study. These specimens were blindly reviewed and reclassified using TPS 2.0. The correlation between TPS 2.0, ORS and histopathologic follow‐up was assessed.

Results

The UUT cytology specimens corresponded to 21 (40.4%) high‐grade urothelial carcinoma (HGUC), 27 (51.9%) low‐grade urothelial carcinoma (LGUC) and 4 (7.7%) benign cases on follow‐up. For HGGC cases, the associated TPS categories included unsatisfactory (n = 1, 4.8%), negative for HGUC (NHGUC; n = 3, 14.3%), atypical urothelial cells (AUC; n = 6, 28.6%), suspicious for HGUC (SHGUC; n = 3, 14.3%) and HGUC (n = 8, 38.1%), while ORS categorised the specimens as unsatisfactory (n = 1, 4.8%), negative for malignant cells (NFMC; n = 3, 14.3%), AUC (n = 5, 23.8%), low‐grade urothelial carcinoma (LGUC; n = 0, 0%), SHGUC (n = 5, 23.8%) and HGUC (n = 7, 33.3%). The risks of high‐grade malignancy among cytologic categories were similar between ORS and TPS (p > 0.05). The majority of LGUC were classified as AUC similarly by ORS and TPS (55.6% vs. 59.3%).

Conclusions

Our study demonstrated comparable performance between TPS 2.0 and ORS for UUT cytology specimens. Cytological diagnosis of UUT specimens remains challenging, especially for LGUC.
Multi‐criteria evolutionary optimization of a traffic light using genetics algorithm and teaching‐learning based optimization
Authors: Yektamoghadam Hossein , Nikoofard Amirhossein , Behzadi Masoumeh , Khosravy Mahdi , Dey Nilanjan , Witkowski Olaf
Published: November 2023

Today, the development of urbanization and increasing the number of vehicles has resulted in displeased consequences like traffic congestion and vehicle queuing. The vast majority of countries in the world encounter the challenge of the explosive rise in traffic demand. In this regard, it is necessary to meet traffic demand in transport networks, especially in metropolitans. In traffic management and shortening the trip duration, traffic lights on the signalized intersections play an essential role in urban pathways. This work provides a multi‐criteria decision‐making method for optimum traffic light control in an isolated corner. The main idea involves establishing a set of sub‐optimal solutions for traffic light timing and selecting the best one among the diverse solutions. We have mathematically modelled the problem as an optimization problem to achieve an optimal solution with less waiting time for vehicles in intersections and the lowest cost. Genetic algorithm (GA) and Teaching‐Learning‐based Optimization (TLBO) are utilized for each phase to create a set of suitable timing scenarios. The Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method is used to identify the best scenario, considering both waiting vehicles and traffic capacity as decision criteria. Its efficiency has been demonstrated over three different traffic volumes. Also, in a real‐world implementation, its practical capability has been approved at a crossroads in Mashhad, Iran. The simulations indicate the improvement in the number of vehicles waiting behind the crossroad and the traffic capacity by 10% and 6.76% compared to the existing signal timing of the studied intersection, respectively.
Learning Chinese as a foreign language: An introduction
Authors: House Juliane , Kádár Dániel Z.
Published: November 2023

In this introductory paper, we first present the background of the present special issue dedicated to Willis Edmondson. We first point out why Edmondson provided a ground‐breaking contribution to the field of applied linguistics and why it is particularly timely to edit a special issue centering on his framework. We also argue that Edmondson's bottom‐up and strictly language‐anchored view on speech acts and interaction is particularly useful to examine the learning of Chinese as a foreign language, by going beyond exoticizing and overgeneralizing views of the Chinese linguaculture. Second, we briefly present what can be regarded as the heart and soul of the Edmondsonian framework, that is, a typology of speech acts and a related procedure through which the relationship between speech acts in interaction can be captured. Third, we present a research procedure that we outlined in our previous work, and which helps implementing the Edmondsonian model in the pragmatic study of foreign language learning. Finally, we present the contents of the special issue.
Juvenile hormone inhibits adult cuticle formation in Drosophila melanogaster through Kr‐h1/Dnmt2‐mediated DNA methylation of Acp65A promoter
Authors: He Qianyu , Fan Xiaochun , Wang Shunxin , Chen Shanshan , Chen Jinxia
Published: November 2023

Differentiation of imaginal epidermal cells of Drosophila melanogaster to form adult cuticles occurs at approximately 40–93 h after puparium formation. Juvenile hormone (JH) given at pupariation results in formation of a second pupal cuticle in the abdomen instead of the adult cuticle. Although the adult cuticle gene Acp65A has been reported to be down‐regulated following JH treatment, the regulatory mechanism remains unclear. Here, we found that the JH primary response gene Krüppel homologue 1 (Kr‐h1) plays a vital role in the repression of adult cuticle formation through the mediation of JH action. Overexpression of Kr‐h1 mimicked—while knocking down of Kr‐h1 attenuated—the inhibitory action of JH on the formation of the adult abdominal cuticle. Further, we found that Kr‐h1 inhibited the transcription of Acp65A by directly binding to the consensus Kr‐h1 binding site (KBS) within the Acp65A promoter region. Moreover, the DNA methyltransferase Dnmt2 was shown to interact with Kr‐h1, combined with the KBS to promote the DNA methylation of sequences around the KBS, in turn inhibiting the transcription of Acp65A. This study advances our understanding of the molecular basis of the “status quo” action of JH on the Drosophila adult metamorphosis.
Genetic and context-specific effects on individual inhibitory control performance in the guppy (Poecilia reticulata)
Authors: Prentice Pamela M. , Thornton Alex , Kolm Niclas , Wilson Alastair J.
Published: November 2023

Among-individual variation in cognitive traits, widely assumed to have evolved under adaptive processes, is increasingly being demonstrated across animal taxa. As variation among individuals is required for natural selection, characterizing individual differences and their heritability is important to understand how cognitive traits evolve. Here, we use a quantitative genetic study of wild-type guppies repeatedly exposed to a ‘detour task’ to test for genetic variance in the cognitive trait of inhibitory control. We also test for genotype-by-environment interactions (GxE) by testing related fish under alternative experimental treatments (transparent vs. semi-transparent barrier in the detour-task). We find among-individual variation in detour task performance, consistent with differences in inhibitory control. However, analysis of GxE reveals that heritable factors only contribute to performance variation in one treatment. This suggests that the adaptive evolutionary potential of inhibitory control (and/or other latent variables contributing to task performance) may be highly sensitive to environmental conditions. The presence of GxE also implies that the plastic response of detour task performance to treatment environment is genetically variable. Our results are consistent with a scenario where variation in individual inhibitory control stems from complex interactions between heritable and plastic components.

Abstract

We use a quantitative genetic study to examine variation in cognitive performance in wild-type guppies. We show among-individual variation in detour task performance, consistent with differences in inhibitory control as well as plasticity to visual information context. Heritable variation was also detected but GxE means this is limited to the low information treatment. Our results suggest the adaptive evolutionary potential of inhibitory control may be highly sensitive to environmental context.
Diagnostic work‐up and surgical management of insulinoma: A retrospective analysis from a tertiary referral center
Authors: Andreasi Valentina , Partelli Stefano , Muffatti Francesca , Battistella Anna , Fermi Francesca , Balzano Gianpaolo , Crippa Stefano , Tamburrino Domenico , Pecorelli Nicolò , De Cobelli Francesco , Arcidiacono Paolo Giorgio , Falconi Massimo
Published: November 2023

Insulinoma is a multifaceted disease that poses several challenges in terms of clinical presentation, diagnostic work‐up, and surgical management. The aim of this study was to describe diagnostic work‐up, surgical management, and postoperative outcomes of patients with insulinoma. All consecutive patients who underwent surgery for insulinoma at San Raffaele Hospital (Milan, Italy) between January 2008 and January 2022 were included. Overall, 98 patients were considered. The median delay between presenting symptoms and insulinoma diagnosis was 10 months (IQR, 4–21). Insulinoma diagnosis was made at our Institution in 45 patients, 20 of whom referred within 6 months from symptoms onset. In this subgroup, the median interval between symptoms presentation and insulinoma diagnosis was 4 months (IQR, 2–6), as compared to 14 months (IQR, 10–26) in patients (n = 25) who referred to our institution after 6 months from symptoms onset (p < .001). The insulinoma was localized preoperatively in all the cases. All patients underwent ≥1 high‐quality imaging: computed tomography (CT: n = 87, sensitivity 84%), magnetic resonance imaging (MRI: n = 55, sensitivity 85%) and endoscopic ultrasound (EUS: n = 79, sensitivity 100%). MRI identified the tumor in eight patients with negative CT. EUS localized the insulinoma in three patients with negative CT and negative MRI. Parenchyma‐sparing resections were performed in 41 patients. Contact with major vessels, lesion close to Wirsung duct and suspect of malignancy were the main reasons to perform a formal resection. An early referral to high‐volume centers is important for reducing diagnostic delay in patients with insulinoma. The diagnostic work‐up of insulinoma frequently requires several imaging modalities to be performed, with EUS being the most sensitive one. Parenchyma‐sparing surgery for insulinoma should be performed whenever technically and oncologically feasible.
Fracturing walls, not identities: The power of John Green's fully human representations of disability in The Fault in Our Stars
Authors: Pearson Amy
Published: November 2023

In my paper, I argue that young‐adult author John Green recognizes the problematic ways conventional literary representations of people with disabilities contribute to the dehumanization of people with impairments. Furthermore, I suggest that Green's vibrant characters in The Fault in Our Stars and the connection readers have formed with them illuminate the power that realistic and, therefore, necessarily complex representations of characters with disabilities hold in transforming how people approach others with impairments, and, ultimately, how people with disabilities construct their own identities.
Follistatin (FST) is expressed in buffalo (Bubalus bubalis) ovarian follicles and promotes oocyte maturation and early embryonic development
Authors: Wang Haoxin , Chen Weili , Shen Penglei , Feng Yun , Shi Deshun , Lu Fenghua
Published: November 2023

Follistatin (FST), a member of the transforming growth factor‐β (TGF‐β) superfamily, has been identified as an inhibitor of follicle‐stimulating hormone. Previous studies showed that it plays an important role in animal reproduction. Therefore, this study aims to investigate its effect on the maturation of buffalo oocytes in vitro, and the underlying mechanism of FST affecting oocyte maturation was also explored in buffalo cumulus cells. Results showed that FST was enriched in the ovary and expressed at different stages of buffalo ovarian follicles as well as during oocyte maturation and early embryo development. The FST expression level was up‐regulated in MII buffalo oocytes compared with the GV stage (p < .05). To study the effects of FST on buffalo oocytes' maturation and early embryonic development, we added the pcD3.1 skeleton vector and PCD3.1‐EGFP‐FST vector into the maturation fluid of buffalo oocytes, respectively. It was demonstrated that FST promoted the in vitro maturation rate of buffalo oocytes and the blastocyst rate of embryos cultured in vitro (p < .05). By interfering with FST expression, we discovered that FST in cumulus cells plays a crucial role in oocyte maturation. Interference with the FST expression during the buffalo oocyte maturation did not affect the first polar body rate of buffalo oocyte (p > .05). In contrast, the location of mitochondria in oocytes was abnormal, and the cumulus expansion area was reduced (p < .05). After parthenogenetic activation, the cleavage and blastocyst rates of the FST‐interfered group were reduced (p < .05). Furthermore, RT‐qPCR was performed to investigate further the underlying mechanism by which FST enhances oocyte maturation. We found that overexpression of FST could up‐regulate the expression level of apoptosis suppressor gene Bcl‐2 and TGF‐β/SMAD pathway‐related genes TGF‐β, SMAD2, and SMAD3 (p < .05). In contrast, the expression levels of SMAD4 and pro‐apoptotic gene BAX were significantly decreased (p < .05). The FST gene could affect buffalo oocyte maturation by regulating the oocyte mitochondria integrity, the cumulus expansion, cumulus cell apoptosis, and the expression levels of TGF‐β/SMAD pathway‐related genes.