bluuebunny/crossref_metadata_2025 huggingface dataset:
CCR5 deficiency: decreased neuronal resilience to oxidative stress and increased risk of vascular dementia
Authors: Tournier Benjamin B. , Sorce Silvia , Marteyn Antoine , Ghidoni Roberta , Benussi Luisa , Binetti Giuliano , Herrmann François R , Krause Karl-Heinz , Zekry Dina
Published: February 2023

Introduction

As the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia.

Methods

Logistic regression models with CCR5 and ApoE polymorphisms were applied to 205 cognitively normal and 189 dementia patients included in Geneva. The impact of oxidative stress onCcr5expression and cell death was assessed in mice neurons.

Results

CCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an eleven-fold greater risk of vascular and mixed dementia. Oxidative stress induced cell death inCcr5-/-mice neurons.

Discussion

We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.
A 10-year review of antihypertensive prescribing practices after stroke and the associated disparities from the Florida Stroke Registry
Authors: Perue Gillian Gordon , Ying Hao , Bustillo Antonio , Zhou Lili , Gutierrez Carolina M. , Wang Kefeng , Gardener Hannah E , Krigman Judith , Jameson Angus , Foster Dianne , Dong Chuanhui , Rundek Tatjana , Rose David Z , Romano Jose G. , Alkhachroum Ayham , Sacco Ralph L. , Asdaghi Negar , Koch Sebastian
Published: February 2023

Background

Guideline based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescribers’ blood pressure medication choice adheres to clinical practice guidelines (Prescribers’-Choice Adherence).

Methods

The Florida Stroke registry (FSR) utilizes statewide data prospectively collected for all acute stroke admissions. Based on established guidelines we defined optimal Prescribers’-Choice Adherence using the following hierarchy of rules: 1) use of an angiotensin inhibitor (ACEI) or angiotensin receptor blocker (ARB) as first-line antihypertensive among diabetics; 2) use of thiazide-type diuretics or calcium channel blockers (CCB) among African-American patients; 3) use of beta-adrenergic blockers (BB) among patients with compelling cardiac indication (CCI) 4) use of thiazide, ACEI/ARB or CCB class as first-line in all others; 5) BB should be avoided as first line unless CCI.

RESULTS

A total of 372,254 cases from January 2010 to March 2020 are in FSR with a diagnosis of acute ischemic, hemorrhagic stroke, transient ischemic attack or subarachnoid hemorrhage; 265,409 with complete data were included in the final analysis. Mean age 70 +/-14 years, 50% female, index stroke subtype of 74% acute ischemic stroke and 11% intracerebral hemorrhage. Prescribers’-Choice Adherence to each specific rule ranged from 48-74% which is below quality standards of 85%. There were race-ethnic disparities with only 49% Prescribers choice Adherence for African Americans patients.

Conclusion

This large dataset demonstrates consistently low rates of Prescribers’-Choice Adherence over 10 years. There is an opportunity for quality improvement in hypertensive management after stroke.
Gut Microbiome Composition Reveals the Distinctiveness between the Bengali people and the Indigenous Ethnicities in Bangladesh
Authors: Ahammad Ishtiaque , Rahman Anisur , Chowdhury Zeshan Mahmud , Bhattacharjee Arittra , Dewan Gourab , Talukder Shiny , Das Keshob Chandra , Keya Chaman Ara , Hossain Mohammad Uzzal , Salimullah Md.
Published: February 2023

Human gut microbiome is influenced by ethnicity and other factors. In this study, we have explored the gut microbiome of Bengali population (n=13) and four Tibeto-Burman indigenous communities-Chakma (n=15), Marma (n=6), Khyang (n=10), and Tripura (n=11) using 16S rRNA amplicon sequencing. A total of 19 characterized phyla were identified in 5 cohorts, withFirmicutesandBacteroidetesbeing the most prevalent. At the genus level, the abundance ofPrevotellawas relatively similar across all ethnicities. However, the Chakma population demonstrated higherBacteroidesabundance. Chakma people were more distinct than other ethnicities and exhibited a higher quantity of differentially abundant microbial features. The Bengali population had relatively low bacterial richness and‘FirmicutestoBacteroidetesratio’ than others with lower qualitative microbial diversity. A phylosymbiotic link between Bangladeshi indigenous people and certain ethnic groups in India have also been discovered. A comparative analysis between all Bangladeshi samples (n=55) and several tropical and subtropical countries (n=132) such as Australia, Egypt, Indonesia, Malaysia, Mexico, Thailand, and Vietnam revealed that the gut microbiota profile of Bangladeshi people is remarkably distinct from others. The insights from this study will aid further epidemiological and translational research.
μ-PBWT: Enabling the Storage and Use of UK Biobank Data on a Commodity Laptop
Authors: Cozzi Davide , Rossi Massimiliano , Rubinacci Simone , Köppl Dominik , Boucher Christina , Bonizzoni Paola
Published: February 2023

Motivation

The positional Burrows-Wheeler Transform (PBWT) has been introduced as a key data structure for indexing haplotype sequences with the main purpose of finding maximal haplotype matches inhsequences containingwvariation sites in-time with a significant improvement over classical quadratic time approaches. However the original PBWT data structure does not allow queries over the modern biobank panels of haplotypes consisting of several millions of haplotypes, as they must be kept entirely in memory.

Results

In this paper, we present a method for constructing the run-length encoded PBWT for memory efficient haplotype matching. We implement our method, which we refer to asμ-PBWT, and evaluate it on datasets of 1000 Genome Project and UK Biobank data. Our experiments demonstrate that theμ-PBWTreduces the memory usage up to a factor of 25 compared to the best current PBWT-based indexing. In particular,μ-PBWTproduces an index that stores high-coverage whole genome sequencing data of chromosome 20 in half the space of its BCF file. In addition,μ-PBWTis able to index a dataset with 2 million haplotypes and 2.3 million sites in 4 GB of space, which can be uploaded in 20 seconds on a commodity laptop.μ-PBWTis an adaptation of techniques for the run-length compressed BWT for the PBWT (RLPBWT) and it is based on keeping in memory only a small representation of the RLPBWT that still allows the efficient computation of set maximal matches (SMEMs) over the original panel.

Availability

Our implementation is open source and available athttps://github.com/dlcgold/muPBWT. The binary is available athttps://bioconda.github.io/recipes/mupbwt/README.html

Contact

Paola Bonizzonipaola.bonizzoni@unimib.it
Temporal Notch signaling regulates mucociliary cell fates through Hes-mediated competitive de-repression
Authors: Brislinger-Engelhardt Magdalena Maria , Lorenz Fabian , Haas Maximilian , Bowden Sarah , Tasca Alexia , Kreutz Clemens , Walentek Peter
Published: February 2023

Tissue functions are determined by the types and ratios of cells present, but little is known about self-organizing principles establishing correct cell type compositions. Mucociliary airway clearance relies on the correct balance between secretory and ciliated cells, which is regulated by Notch signaling across mucociliary systems. Using the airway-likeXenopusepidermis, we investigate how cell fates depend on signaling, how signaling levels are controlled, and how Hes transcription factors regulate cell fates. We show that four mucociliary cell types each require different Notch levels and that their specification is initiated sequentially by a temporal Notch gradient. We describe a novel role for Foxi1 in the generation of Delta-expressing multipotent progenitors through Hes7.1. Hes7.1 is a weak repressor of mucociliary genes and overcomes maternal repression by the strong repressor Hes2 to initiate mucociliary development. Increasing Notch signaling then inhibits Hes7.1 and activates first Hes4, then Hes5.10, which selectively repress cell fates. We have uncovered a self-organizing mechanism of mucociliary cell type composition by competitive de-repression of cell fates by a set of differentially acting repressors. Furthermore, we present anin silicomodel of this process with predictive abilities.
The response time paradox in functional magnetic resonance imaging analyses
Authors: Mumford Jeanette Alane , Bissett Patrick G. , Jones Henry M. , Shim Sunjae , Rios Jaime Ali H. , Poldrack Russell A.
Published: February 2023

The functional MRI (fMRI) signal is a proxy for an unobservable neuronal signal, and differences in fMRI signals on cognitive tasks are generally interpreted as reflecting differences in the intensity of local neuronal activity. However, changes in either intensity or duration of neuronal activity can yield identical differences in fMRI signals. When conditions differ in response times (RTs), it is thus impossible to determine whether condition differences in fMRI signals are due to differences in the intensity of neuronal activity or to potentially spurious differences in the duration of neuronal activity. The most common fMRI analysis approach ignores RTs, making it difficult to interpret condition differences that could be driven by RTs and/or intensity. Because differences in response time are one of the most important signals of interest for cognitive psychology, nearly every task of interest for fMRI exhibits RT differences across conditions of interest. This results in a paradox, wherein the signal of interest for the psychologist is a potential confound for the fMRI researcher. We review this longstanding problem, and demonstrate that the failure to address RTs in the fMRI time series model can also lead to spurious correlations at the group level related to RTs or other variables of interest, potentially impacting the interpretation of brain-behavior correlations. We propose a simple approach that remedies this problem by including RT in the fMRI time series model. This model separates condition differences from RT differences, retaining power for detection of unconfounded condition differences while also allowing the identification of RT-related activation. We conclude by highlighting the need for further theoretical development regarding the interpretation of fMRI signals and their relationship to response times.
Scanning electron microscopy of human islet cilia
Authors: Polino Alexander J. , Sviben Sanja , Melena Isabella , Piston David W. , Hughes Jing
Published: February 2023

Human islet primary cilia are vital glucose-regulating organelles whose structure remains uncharacterized. Scanning electron microscopy (SEM) is a useful technique for studying the surface morphology of membrane projections like primary cilia, but conventional sample preparation does not reveal the sub-membrane axonemal structure which holds key implications for cilia function. To overcome this challenge, we combined SEM with membrane-extraction techniques to examine cilia in native human islets. Our data show well-preserved cilia subdomains which demonstrate both expected and unexpected ultrastructural motifs. Morphometric features were quantified when possible, including axonemal length and diameter, microtubule conformations and chirality. We further describe a novel ciliary ring, a structure that may be a specialization in human islets. Key findings are correlated with fluorescence microscopy and interpreted in the context of cilia function as a cellular sensor and communications locus in pancreatic islets.
Intracellular Amyloid-β in the Normal Rat Brain and Human Subjects
Authors: Kobro-Flatmoen Asgeir , Hormann Thea Meier , Gouras Gunnar
Published: February 2023

Amyloid-beta (Aβ) is a normal product of neuronal activity, and the two most common variants are 40 or 42 residues long. Of these, the 42 residue-version (Aβ42) is normally less abundant but more prone to self-aggregate, and is thought to cause Alzheimer’s disease (AD). Much knowledge about AD-pathogenesis comes from the study of rodents made to model aspects of the disease by expressing AD-relevant human transgenes, like human amyloid precursor protein (APP) containing mutations that drive up Aβ production or increase the Aβ42/40 ratio and thereby causes AD. Yet, when it comes to the normal expression of Aβ42 in rodent brains, surprisingly little is known. Here we characterize the expression of Aβ42 throughout the brain of normal, outbred Wistar rats, including animals from 3-18 months of age. We find that intracellular Aβ42 (iAβ42) is present in neurons located throughout the brain at all ages of normal Wistar rats, but that the levels vary greatly between brain regions. In cortex, we observe the highest levels of iAβ42 in neurons that are part of layer II of the entorhinal cortex (EC), along with neurons in the hippocampus, closely followed by neurons in the somatosensory cortex. Among subcortical structures, we observe the highest levels iAβ42 in the locus coeruleus. In order to explore whether the striking presence of iAβ42 in rat EC also holds true in human subject free of neurological disease, we examined EC of six such cases ranging from ages 20-88 years. In all six cases, we find that iAβ42 is present in EC layer II-neurons.

Our findings support two conclusions about iAβ42. First, iAβ42 is present in neurons of wild-type Wistar rats and is restricted to the same structures where iAβ accumulates, and Aβ-plaques form, in a much used AD model based on Wistar rats (the McGill-R-Thy1-APP rat model). The difference between wild-type Wistar rats and these AD model rats, with respect to Aβ42, is therefore a quantitative one rather that a qualitative one. This indicates that the McGill rat model in fact models the underlying wild-type neuronal population-specific vulnerability to Aβ42-accumulation. Second, because the McGill rat model closely mimics the human AD-associated spatiotemporal sequence of amyloid plaque deposition, this model may offer a useful representation of the pre-plaque neuronal accumulation of iAβ42. Our findings in human cases are in line with prior findings, and substantiate the notion that neurons in layer II of EC are vulnerable to accumulation of iAβ42.
The maternal microbiome promotes placental development in mice
Authors: Pronovost Geoffrey N. , Telang Sahil S. , Chen Angela S. , Coley Elena J.L. , Vuong Helen E. , Williams Drake W. , Yu Kristie B. , Rendon Tomiko K. , Paramo Jorge , Kim Reuben H. , Hsiao Elaine Y.
Published: February 2023

The maternal microbiome is an important regulator of gestational health, but how it impacts the placenta as the interface between mother and fetus remains unexplored. Here we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate angiogenesis-related tube formation by endothelial cells and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.
How important are concurrent vehicle control groups in (sub)chronic non-human primate toxicity studies conducted in pharmaceutical development? An opportunity to reduce animal numbers
Authors: Mecklenburg Lars , Lenz Sarah , Hempel Georg
Published: February 2023

Safety assessment of human pharmaceuticals demands extensive animal experiments before a compound can be tested in patients or released on the market. Such experiments typically include concurrent vehicle control groups. Reconsidering the need for concurrent controls could support the strive to reduce the use of animals for scientific purposes. We reviewed reports from 20 (sub)chronic toxicity studies that were conducted in non-human primates (NHP) to characterize hazards of novel human pharmaceuticals. Firstly, we determined the toxicological endpoints that were identified to characterize the hazard. Secondly, we evaluated if the hazard could have been identified without reference to the concurrent controls. Thirdly, we employed an alternative statistical method to test for any significant change related to dose level or time. We found that toxicologically relevant hazards were identifiable without reference to concurrent controls, because individual measurements could be compared with pre-dosing values or because individual measurements could be compared to historical reference data. Effects that could not be evaluated without reference to concurrent controls were clinical observations and organ weights for which appropriate historical reference data was not available, or immune responses that could not be compared to pre-dosing measurements because their magnitude would change over time. Our investigation indicates that concurrent control groups in (sub)chronic NHP toxicity studies are of limited relevance for reaching the study objective. Under certain conditions, regulatory (sub)chronic NHP toxicity studies represent a good starting point to implement virtual control groups rather than concurrent control groups in nonclinical safety testing.
Intraspecific proteomic profiling and potential biological activities of the honey bee hemolymph
Authors: Elfar Salma A. , Bahgat Iman M. , Shebl Mohamed A. , Lihoreau Mathieu , Tawfik Mohamed M.
Published: February 2023

Pollinator declines have raised major concerns for the maintenance of biodiversity and food security, calling for a better understanding of environmental factors that affect their health. Here we used hemolymph analysis, a cheap, simple, yet powerful approach, to monitor the health state of Western honey beesApis mellifera. We evaluated the intraspecific proteomic variations and the biological activities of hemolymph of bees collected from four Egyptian localities characterized by different food diversities and abundances. Lowest protein concentrations and the weakest bioactivities were recorded in hemolymph of bees artificially fed sucrose solution and no pollen. By contrast, highest protein concentrations and activities were recorded in bees that had the opportunity to feed on various natural resources. While future studies should expand comparisons to honey bee populations exposed to more different diets, our results strongly suggest hemolymph samples can be used as reliable indicators of bee nutrition and health.
Copper drives prion protein phase separation and modulates aggregation
Authors: do Amaral Mariana Juliani , Passos Aline Ribeiro , Mohapatra Satabdee , da Silva Taiana Sousa Lopes , Carvalho Renato Sampaio , Almeida Marcius da Silva , de Sá Pinheiro Anderson , Wegmann Susanne , Cordeiro Yraima
Published: February 2023

Prion diseases are characterized by prion protein (PrP) transmissible aggregation and toxicity in the brain. The physiological function of PrP seems related to sequestering and internalization of redox-active Cu2+. It is unclear whether Cu2+contributes to PrP aggregation, recently shown to be mediated by PrP condensation. We investigated the role of Cu2+and oxidation in PrP condensation and aggregation using multiple biophysical and biochemical methods. We find that Cu2+promotes PrP condensation at the cell surface andin vitrothrough co-partitioning. Molecularly, Cu2+inhibited PrP β-structure and hydrophobic residues exposure. Oxidation, induced by H2O2, triggered liquid-to-solid transition of PrP:Cu2+condensates and promoted amyloid-like PrP aggregation. In cells, overexpression of PrPCinitially protected against Cu2+cytotoxicity but led to PrPCaggregation upon extended copper exposure. Our data suggest that PrP condensates function as a buffer for copper that prevent copper toxicity but can transition into PrP aggregation at prolonged oxidative stress.
A method for rapid nanobody screening with no bias of the library diversity
Authors: Tao Zhiqing , Zhao Xiaoling , Wang Huan , Zhang Juan , Jiang Guosheng , Yu Bin , Chen Yihao , Zhu Mingjun , Long Junli , Yin Lei , Zhang Xu , Liu Maili , He Lichun
Published: February 2023

Nanobody refers to the variable domain of heavy-chain-only antibodies. The distinctive advantages of nanobodies including small size, feasible expression inEscherichia coli(E. coli), and superior stability make them promising tools for applications in scientific research and therapies. So far, the screening and expression of nanobodies are mainly following similar methods used for conventional antibodies, suffering from amplification-caused losses of the diversity of libraries and requirements of subcloning of interests into the expression vector. Here, based on the unique properties of nanobodies, we developed an integrated method to screen and express nanobodies simultaneously with no bias of the library diversity. The library of nanobodies was cloned and secretively expressed into the culture medium. Target specifical binding nanobodies were isolated through 1-3 rounds of dilution and regrown steps in a way following the Poisson distribution to ensure no positive clones were dismissed, while the population of positive clones increased by more than 10 folds upon each round of dilution. Ultimately, 5 nanobodies against the death domain receptor 5 (DR5) and 5 nanobodies against thePyrococcus furiosus(Pfu) DNA polymerase were produced directly out of their immunized libraries, respectively. Additionally, our approach allowed nanobody screening even without any specialized instruments/devices, demonstrating general applicability in the routine production of monoclonal nanobodies for diverse biomedical applications.
Evidence for an aquatic origin of influenza virus and the orderArticulavirales
Authors: Petrone Mary E. , Parry Rhys , Mifsud Jonathon C. O. , Van Brussel Kate , Vorhees Ian , Richards Zoe T. , Holmes Edward C.
Published: February 2023

The emergence of novel disease-causing viruses in mammals is part of the long evolutionary history of viruses. Tracing these evolutionary histories contextualises virus spill over events and may help to elucidate how and why they occur. We used a combination of total RNA sequencing and transcriptome data mining to extend the diversity and evolutionary history of the orderArticulavirales, which includes the influenza viruses. From this, we identified the first instance ofArticulaviralesin the Cnidaria (including corals), constituting a novel and divergent family that we tentatively named theCnidenomoviridae. This may be the basal group within theArticulavirales. We also extended the known evolutionary history of the influenza virus lineage by identifying a highly divergent, sturgeon-associated influenza virus. This suggests that fish were among the first hosts of influenza viruses. Finally, we substantially expanded the known diversity of quaranjaviruses and proposed that this genus be reclassified as a family (theQuaranjaviridae). We find evidence that vertebrate infectingQuaranjaviridaemay have initially evolved in crustaceans before spilling into terrestrial Chelicerata (i.e., ticks). Together, our findings indicate that theArticulaviraleshas evolved over at least 600 million years, first emerging in aquatic animals. Importantly, the evolution of this order was not shaped by strict virus-host codivergence, but rather by multiple aquatic-terrestrial transitions and substantial host jumps, some of which are still observable today.
The EspN transcription factor is an infection-dependent regulator of the ESX-1 system inM. marinum
Authors: Nicholson Kathleen R. , Cronin Rachel M. , Menon Aruna R. , Jennisch Madeleine K. , Tobin David M. , Champion Patricia A.
Published: February 2023

Bacterial pathogens use protein secretion systems to translocate virulence factors into the host and to control bacterial gene expression. The ESX-1 (ESAT-6 system 1) secretion system facilitates disruption of the macrophage phagosome during infection, enabling access to the cytoplasm, and regulates widespread gene expression in the mycobacterial cell. The transcription factors contributing to the ESX-1 transcriptional network during mycobacterial infection are not known. We showed that the EspM and WhiB6 transcription factors regulate the ESX-1 transcriptional networkin vitrobut are dispensable for macrophage infection byMycobacterium marinum. In this study, we used our understanding of the ESX-1 system to identify EspN, a critical transcription factor that controls expression of the ESX-1 genes during infection, but whose effect is not detectable under standard laboratory growth conditions. Under laboratory conditions, EspN activity is masked by the EspM repressor. In the absence of EspM, we found that EspN is required for ESX-1 function because it activates expression of thewhiB6transcription factor gene, and specific ESX-1 substrate and secretory component genes. Unlike the other transcription factors that regulate ESX-1, EspN is required forM. marinumgrowth within and cytolysis of macrophages, and for disease burden in a zebrafish larval model of infection. These findings demonstrate that EspN is an infection-dependent regulator of the ESX-1 transcriptional network, which is essential for mycobacterial pathogenesis. Moreover, our findings suggest that ESX-1 expression is controlled by a genetic switch that responds to host specific signals.

Importance

Pathogenic mycobacteria cause acute and long-term diseases, including human tuberculosis. The ESX-1 system transports proteins that control the host response to infection and promotes bacterial survival. Although ESX-1 transports proteins, it also controls gene expression in the bacteria. In this study, we identify an undescribed transcription factor that controls the expression of ESX-1 genes, and is required for both macrophage and animal infection. However, this transcription factor is not the primary regulator of ESX-1 genes under standard laboratory conditions. These findings identify a critical transcription factor that controls expression of a major virulence pathway during infection, but whose effect is not detectable with standard laboratory strains and growth conditions.
Inhibiting Bet1-mediated transport of MMP14 to plasma membrane impaired GBM cell invasion
Authors: Luo Yani , Li Jiana , Xiong Yi
Published: February 2023

Purpose

Glioblastoma (GBM) is the most aggressive and common form of brain cancer in adults. GBM is characterised by poor survival as the lack of effective therapies. This research aims to detect the roles of SNAREs in GBM and improve our knowledge of targeting therapy for GBM.

Materials and methods

the expression of SNAREs and their correlation with overall survival (OS) in GBM are investigated using the GEPIA. The level of BET1 in GBM cell lines was tested by RT-qPCR, and its biological functions in GBM cells were tested by Transwell assay and CCK8 kit. The effect of BET1 on the location of MMP14 is identified by Immunofluorescence.

Results

The expression profile of SNARE family members in GBM tissue is changed dramatically. Among them, the mRNA levels of BET1 and VAMP3 are up-regulated, and their expression negatively correlates with OS. BET1 is also increased in GBM Cell Lines, and it is required for efficient GBM cell migration and invasion partly because it mediates the transport of MMP14 to the plasma membrane.

Conclusion

GBM has highly diffusive and infiltrative ability in nature, making complete surgical resection almost impossible. Our data shows that BET1 is highly expressed in GBM tissue, negatively correlated with OS, and essential for GBM cell migration and invasion. These results indicate that SNARE BET1 may present a potential target for GBM treatment.
Blood-brain barrier water exchange measurements using contrast-enhanced ASL
Authors: Powell Elizabeth , Dickie Ben R. , Ohene Yolanda , Parker Geoff J. M. , Parkes Laura M.
Published: February 2023

A technique for quantifying regional blood-brain barrier (BBB) water exchange rates using contrast-enhanced arterial spin labelling (CE-ASL) is presented and evaluated in simulations and in vivo. The two-compartment ASL model describes the water exchange rate from blood to tissue,kb, but to estimatekbin practice it is necessary to separate the intra- and extravascular signals. This is challenging in standard ASL data owing to the small difference inT1values. Here, a gadolinium-based contrast agent is used to increase thisT1difference and enable the signal components to be disentangled. The optimal post-contrast bloodT1at 3T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof-of-concept data were acquired in six healthy volunteers (five female, age range 24 – 46 years). The sensitivity analysis identified the optimalat 3T as 0.8 s. Simulations showedkbcould be estimated in individual cortical regions with a relative errorϵ< 1% and coefficient of variation CoV = 30 %; however, a high dependence on bloodT1was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit timetA= 1.15±0.49 s, cerebral blood flowf= 58.0±14.3 ml blood / min / 100 ml tissue, water exchange ratekb= 2.32 ± 2.49 s−1. CE-ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measuredT1values.
Somatic disinhibition of granule cells improves information transmission and pattern separation in the dentate gyrus
Authors: Estarellas Cristian , Álvarez-Salvado Efrén , Pérez-Cervera Laura , Mirasso Claudio R. , Canals Santiago
Published: February 2023

Cortical circuits operate in a tight excitation/inhibition balance. This balance is relaxed during learning processes, but neither the mechanism nor its impact on network operations are well understood. In the present study, we combinedin-vivoandin-vitroneuronal recordings with computational modelling and demonstrated that synaptic plasticity in the afferents from the entorhinal cortex (EC) to the dentate gyrus (DG), in addition to strengthening the glutamatergic inputs into granule cells (GCs), depressed perisomatic inhibition. Computational modelling revealed a functional reorganization in the inhibitory network that explained several experimental findings, including depression of the feed-forward inhibition.In vitroresults confirmed a perisomatic dominance of the inhibitory regulation with important functional consequences. It favoured GCs burst firing, improved reliability of input/output transformations and enhanced separation and transmission of temporal and spatial patterns in the EC-DG-CA3 network.
Ketosynthase engineering enhances activity and shifts specificity towards non-native extender units in type I linear polyketide synthase
Authors: Gerlinger Patrick D. , Angelidou Georgia , Paczia Nicole , Erb Tobias J.
Published: February 2023

Engineering modular type I polyketide synthases (PKS) for the targeted incorporation of non-natural substrates to create variations in the polyketide backbone is a long-standing goal of PKS research. Thus far, most approaches focused on engineering the acyltransferase domain (AT) of PKS, whereas the effects of other ubiquitous domains such as the ketosynthase domain (KS) have received much less attention. In this work, we investigated the effects of thirteen active site substitutions in the module 3 KS (KS3) of the 6-deoxyerythronolide B synthase (DEBS) on incorporation of non-natural extender unitsin vitro. Using a truncated and a complete DEBS assembly line, we show that substitutions of F263 in KS3 invert specificity up to 1,250-fold towards incorporation of non-natural extender units in the terminal position. In contrast, substitutions of I444 in KS3 show up to 8-fold increased production of 6-deoxyerythonolide B (6-dEB) analogues with non-natural extender units at internal positions. The latter notably without compromising overall productivity of the assembly line. Our study further elucidates the underlying mechanisms for these different behaviors, highlighting the potential of KS engineering for the production of designer polyketides in the future.
Oxidation behavior of the T91 ferritic/martensitic steel and 304 austenitic stainless steel in supercritical water
Authors: Wu Jing , An Xuguang , Wang Hui
Published: February 2023

Purpose

This study aims to report the oxidation behaviors of the T91 ferritic/martensitic steel (T91 steel) and 304 austenitic stainless steel (304 steel) in supercritical water (SCW) at 600°C.

Design/methodology/approach

The microstructure, elemental distribution and phase structure of the oxidation layers derived from the corrosion of the T91 steel and 304 steel were analyzed by scanning electron microscopy, Oxford Instrument X-ray spectroscopy, electron scattered diffraction and transmission electron microscopy.

Findings

The oxidation layers on the T91 steel and 304 steel have duplex structure. The two steels all suffer internal oxidation, and the phase of the internal oxidation layers are indexed as Fe-Cr spinel, although their morphologies are different. The formation of a continuous Cr-rich layer is not detected because of the relatively low Cr content of the steels, which is attributed to the corrosion property.

Originality/value

The accelerated corrosion and corrosion mechanism of the T91 steel and 304 steel with low Cr occurring in SCW at 600°C was clarified.
Relationship between earnings management and corporate risk in Latin-American firms
Authors: Muñoz Mendoza Jorge Andrés , Veloso Ramos Carmen Lissette , Sepúlveda Yelpo Sandra María , Delgado Fuentealba Carlos Leandro , Cornejo-Saavedra Edinson Edgardo
Published: February 2023

Purpose

The purpose of this article is to analyze the effects of accruals-based earnings management (AEM) and institutional and financial development on corporate risk of Latin-American firms.

Design/methodology/approach

The GMM estimator was used according to Arellano and Bond (1991) for panel data on a sample of 914 non-financial companies between 2005 and 2017.

Findings

AEM practices significantly increase corporate risk. This result indicates that the risk increase is associated to weakening of the corporate governance of companies. Positive discretionary accruals also have the same impact on corporate risk. In addition, accrual-based earnings management has a non-linear impact on corporate risk. Higher institutional and financial development systemically reduces the risk of Latin American firms. Institutional development can mitigate the effects of earnings management on corporate risk.

Originality/value

These results support that AEM represents a practice that managers use to weaken firms' corporate governance and expropriate wealth from shareholders. These practices promote higher firm's risk. However, the institutional and financial development reduces the corporate risk and contributes to mitigate the impact of AEM on it. These results have relevant implications for firms' corporate governance because they warn the relevance to control AEM practices and its impact over corporate risk perception by investors. These results also are relevant to policymakers because they orient the financial policies design to strengthen the institutional and financial development as a systematic way to reduce the firm's risk.
“She’s all about her words”: one teacher’s efforts to sustain her students’ cultures through discourse
Authors: Patterson Ashley N.
Published: February 2023

Purpose

This study aims to illustrate how one-sixth grade language arts teacher transforms the theory of culturally sustaining pedagogy (CSP) into practice, an effort made visible through classroom discourse.

Design/methodology/approach

This classroom discourse inquiry is guided by tools of reconstructive discourse analysis which encourage a complex consideration of communicative efforts with intent to deconstruct them in the process of uncovering how oppressive social power structures are maintained. Additionally, reconstructive discourse analysis drives attention to how the data analyzed can reveal both how discourse marks moments where justice is constructed as well as how unjust structures may be reshaped into those that are more equitable.

Findings

In a setting where rapport and trust have been established, intentional teacher-driven classroom discourse influenced the ability of student cultures, namely, their languages, to be sustained in the classroom on their own merits and not merely as a conduit for accessing dominant academic material.

Practical implications

The information presented in this manuscript in the form of analysis of discursive classroom moments provide examples for equity-driven practitioners to engage in similar critically reflective activities with the potential to expose instances of CSPs or to assist in the identification of instances where the taking up of CSPs should sought.

Originality/value

One difficulty in transforming theoretical stances to practical actions stems from oversimplification of CSP and related asset-based pedagogical practices as “just good teaching.” By deconstructing classroom discourse, this study can subsequently reconstruct effective, generative, culturally sustaining approaches to community practice within a classroom learning space.
Backpacker conceptualisation criteria: discussion, clarification and operationalisation proposal
Authors: Martins Márcio Ribeiro , Costa Rui Augusto
Published: February 2023

Purpose

Backpackers can be found all over the world, especially in urban areas where the main enclaves are established. The purpose of this paper is to discuss the operationalisation of the term “backpacker” and present a proposal to conceptualise backpackers and backpackers’ segments based on the operational criteria available in literature to avoid incongruities among researchers.

Design/methodology/approach

Based on a literature review, this study provides a critical review of the backpacker conceptualisation and operationalisation using a methodology divided into three phases, a quantitative analysis based on the Scopus database and a bibliometric analysis coupled with a manual analysis of documents (content analysis).

Findings

Substantial heterogeneity and complexity regarding the conceptualisation of backpacker tourism and its diversified subsegments were evident. For this reason, this paper argues that backpacker tourism can and should continue to be analysed from different perspectives, suitably framed in the theoretical instrument constructed to identify and distinguish the different subsegments through its operationalisation features.

Originality/value

This study provides a practical contribution to all researchers interested in the topic of backpackers proposing the operationalisation of the term backpacker and it subsegments to avoid disparate results and deviations. This contribution will enable the correct and objective assessment of the operationalisation of this concept for researchers, managers and destination management organisations, identifying exactly what phenomenon is to be studied.
Stalking and the impact of labelling “There’s a difference between my offence and a stalker”
Authors: Wheatley Rachael , Underwood Alan
Published: February 2023

Purpose

This paper aims to consider stalking as an offending behaviour and the prevailing narratives associated with this offending behaviour given the increased attention of society and criminal justice. The stereotypes and labels associated with the offending behaviour often sensationalise aspects of those who engage in stalking. Frequently, individuals are portrayed as disturbed, psychopathic, mentally ill, violent and culturally deviant. Sometimes stalking behaviour is perversely downplayed as romantic perseverance. The impact of the stalker label extends outward from the act of marking legal and societal transgression, which impacts upon prospects for rehabilitation and desistance through the shaping of assumptions and maintenance of disempowering connotations.

Design/methodology/approach

This paper considers the impact of the stalking label as a therapeutic-, and perhaps rehabilitation-interfering problem for those who have stalked, drawing on recent research by Wheatley, Winder and Kuss (2020a).

Findings

It discusses the wide-ranging implications of labelling in this context and considers therapeutic approaches for intervention that may encourage rehabilitation engagement, mitigate shame and support desistance from a strengths-based perspective.

Originality/value

This paper draws on recent research exploring stalking case narratives of their own experiences of what drives stalking behaviour, existing labelling literature, and on specialist practitioners’ experiences of working with this group, to influence future thinking and research to address nuances highlighted.
Factors contributing suicide in India
Authors: Patel Avanish Bhai
Published: February 2023

Purpose

The death of a person caused by suicide is a matter of grave concern in contemporary society. Today, a number of people in society are taking their own lives because of many reasons. This study aims to examine the causes of suicide in Indian society using anomie theory.

Design/methodology/approach

The author has applied the content analysis method. The researcher has collated 210 occurrences of suicide from newspapers of Uttar Pradesh between 1 October 2020 and 30 April 2021. The author has recognised the type, patterns and causes of suicide in society by analysing and observing daily news items.

Findings

The result demonstrates that most suicides (16.67%) have been caused by frustration/mental illness, followed by several other causes of suicide such as family problems (13.81%), love affairs (10.00%), poverty (9.05%), harassment (8.57%) and sexual harassment (7.62%). The data shows a major gap in the number of suicide deaths between the genders.

Originality/value

This is an original work of researcher which is basically based on anomie theory.
Using nighttime light data to estimate water evaporation inside buildings in China's urban areas
Authors: Gao Han , Liu Jiahong , Mei Chao , Wang Hao , Shao Weiwei , Liu Chuang
Published: February 2023

Urbanization has a great impact on urban evapotranspiration. Water evaporation inside buildings is an important part of urban water vapor resources and a crucial core of urban hydrological processes. The systematic studies on building water evaporation (BWE) are mostly the method of experimental monitoring. This study proposed a new method to simulate and estimate water evaporation flux inside buildings in urban areas. Based on the nighttime light data and urban per capita gross domestic product (GDP), a new modeling system was built to simulate the total BWE. Building area was calculated using the nighttime light data. And the BWE coefficient Df was estimated according to the important indicator of economic development per capita GDP value. Then the water evaporation inside urban buildings and the spatial distribution of water evaporation inside buildings in typical cities could be obtained. The results showed that the total amount of water evaporation inside buildings in China's urban areas was 24.5 billion m3. Among the 31 provincial capitals in China, Shanghai had the largest BWE of 1.08 billion m3. The minimum water evaporation of buildings in Lhasa was 20.0 million m3. Studies of BWE can assess urban water budgets, support on‐demand allocation of water resources, and provide a fundamental understanding of the relationship between water resources and energy heat island effects in urban areas.
Identification of the haemoglobin level associated with a lower risk of complications after total hip and knee arthroplasty
Authors: Abad‐Motos Ane , Ripollés‐Melchor Javier , Jericó Carlos , Bisbe Elvira , Basora Misericordia , Colomina Maria J. , Becerra‐Bolaños Ángel , Bermúdez‐López María , Massa‐Gómez Cristina , Albaladejo‐Magdalena Javier , Solar‐Herrera Ana , Pérez‐Chrzanowska Hanna , Yárnoz Carlos , Fedriani‐de‐Matos Jacobo José , Blanco‐Del‐Val Beatriz , Fabián‐González David , Bellver Jorge , Redondo‐Enríquez Juan M. , Serrat‐Puyol Jordi , Abad‐Gurumeta Alfredo , Zorrilla‐Vaca Andrés , Aldecoa César , García‐Erce José Antonio ,   the POWER2 Study Investigators Group
Published: February 2023

Background

Preoperative anaemia is associated with poor outcomes in surgical patients, but the preoperative haemoglobin cut‐off that determines lower morbidity in total knee arthroplasty (TKA) and total hip arthroplasty (THA) is not well established.

Methods

Planned secondary analysis of data collected during a multicentre cohort study of patients undergoing THA and TKA in 131 Spanish hospitals during a single 2‐month recruitment period. Anaemia was defined as haemoglobin <12 g dl−1 for females and < 13 g dl−1 for males. The primary outcome was the number of patients with 30‐day in‐hospital postoperative complications according to European Perioperative Clinical Outcome definitions and specific surgical TKA and THA complications. Secondary outcomes included the number of patients with 30‐day moderate‐to‐severe complications, red blood cell transfusion, mortality, and length of hospital stay. Binary logistic regression models were constructed to assess association between preoperative Hb concentrations and postoperative complications, and variables significantly associated with the outcome were included in the multivariate model. The study sample was divided into 11 groups based on preoperative Hb values in an effort to identify the threshold at which increased postoperative complications occurred.

Results

A total of 6099 patients were included in the analysis (3818 THA and 2281 TKA), of whom 8.8% were anaemic. Patients with preoperative anaemia were more likely to suffer overall complications (111/539, 20.6% vs. 563/5560, 10.1%, p < .001) and moderate‐to‐severe complications (67/539, 12.4% vs. 284/5560, 5.1%, p < .001). Multivariable analysis showed preoperative haemoglobin ≥14 g dl−1 was associated with fewer postoperative complications.

Conclusion

Preoperative haemoglobin ≥14 g dl−1 is associated with a lower risk of postoperative complications in patients undergoing primary TKA and THA.