bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling molecular basis for reduced neuraminidase inhibitors susceptibility in highly pathogenic avian influenza A (H5N1) viruses isolated from chickens in India
Authors: Kumar Naveen , Sood Richa , Gupta Chhedi Lal , Bhatia Sandeep , Kumar Manoj , Nagarajan S. , Tosh C. , Murugkar H.V. , Sanyal Aniket
Published: December 2023

The increasing resistance cases in influenza viruses to different classes of antiviral drugs, necessitates the in-depth analysis of molecular interactions governing reduced susceptibility to these drugs. This study explores the molecular basis of neuraminidase inhibitors resistance in avian H5N1 influenza viruses identified in our previous research. Using comprehensive modeling and docking tools, we investigated two isolates—A/chicken/India/85459/2008 (N294S) and A/chicken/WestBengal/142121/2008 (E119A + I117V). The N294S mutation conferred oseltamivir resistance while retaining zanamivir susceptibility, whereas the E119A + I117V mutations led to zanamivir resistance while reducing oseltamivir susceptibility. Molecular interactions analysis unveiled varied fitness levels, hydrogen bonding, and affinity transitions associated with N294S and E119A + I117V mutations. This study provides crucial insights into molecular interactions responsible for reduced susceptibility to neuraminidase inhibitors, which is essential for optimizing antiviral strategies and pandemic preparedness.
Uncovering kinesin dynamics in neurites with MINFLUX
Authors: Wirth Jan Otto , Schentarra Eva-Maria , Scheiderer Lukas , Macarrón-Palacios Victor , Tarnawski Miroslaw , Hell Stefan W.
Published: December 2023

Neurons grow neurites of several tens of micrometers in length, necessitating active transport from the cell body by motor proteins. By tracking fluorophores as minimally invasive labels, MINFLUX is able to quantify the motion of those proteins with nanometer/millisecond resolution. Here we study the substeps of a truncated kinesin-1 mutant in primary rat hippocampal neurons, which have so far been mainly observed on microtubules polymerized on glass coverslips. A gentle fixation protocol largely maintains the structure and surface modifications of the microtubules in the cell. By analyzing the time between the substeps, we identify the ATP-binding state of kinesin-1 and observe the associated rotation of the kinesin-1 head in neurites. We also observed kinesin-1 switching microtubules mid-walk, highlighting the potential of MINFLUX to study the details of active cellular transport.
The histone methyltransferase SETD2 regulates HIV expression and latency through a post-transcriptional mechanism
Authors: Bussey-Sutton Cameron , Ward Airlie , Turner Anne-Marie W , Peterson Jackson J , Emery Ann , Longoria Arturo SR , Margolis David M , Strahl Brian D , Browne Edward P
Published: December 2023

HIV can enter a state of transcriptional latency in CD4 T cells, allowing the virus to evade the host immune system and persist during antiretroviral therapy. Thus, understanding the mechanisms that drive HIV latency, and developing strategies to reactivate viral expression in latently infected cells, are key goals for achieving a cure for HIV. The full spectrum of mechanisms behind the regulation of HIV expression and latency are unclear but include covalent modifications to cellular histones that are associated with the integrated provirus. Here we investigate the role of the SETD2 histone methyltransferase, which deposits H3K36 trimethylation (H3K36me3) cotranscriptionally at genes, in HIV infection. We show that prevention of H3K36me3 through addition of a potent and selective inhibitor of SETD2 (EPZ-719) in human T cells leads to reduced post-integration viral gene expression and accelerated the emergence of a latently infected pool within a population of infected cells. CRISPR/Cas9-mediated knockout of SETD2 in HIV infected primary CD4 T cells confirmed the role of SETD2 in HIV expression. Intriguingly, EPZ-719 exposure also enhanced responsiveness of latently infected cells to latency reversal with the HDAC inhibitor vorinostat. Transcriptomic profiling of EPZ-719 exposed HIV-infected cells identified numerous cellular pathways impacted by EPZ-719. Finally, we show SETD2 inhibition does not affect HIV viral transcription, but instead leads to a shift in the pattern of viral RNA splicing – a result that would be predicted to reduce HIV expression. These results identify SETD2 and H3K36me3 as novel regulators of HIV expression and latency through a post-transcriptional mechanism.
Frequency-dependent phase entrainment of cortical cell types during tACS: Converging modeling evidence
Authors: Gaugain Gabriel , Al Harrach Mariam , Yochum Maxime , Wendling Fabrice , Bikson Marom , Modolo Julien , Nikolayev Denys
Published: December 2023

Background: Transcranial alternating current stimulation (tACS) enables non-invasive modulation of brain activity, holding promise for clinical and research applications. Yet, it remains unclear how the stimulation frequency affects various neuron types. Objective: To quantify the frequency-dependent behavior of key neocortical cell types. Methods: We used both detailed (anatomical multicompartments) and simplified (three compartments) single-cell modeling approaches based on the Hodgkin-Huxley formalism to study neocortical excitatory and inhibitory cells under various-amplitude tACS frequencies within the 5-50 Hz range at rest and during basal 10 Hz activity. Results: L5 pyramidal cells (PC) exhibited the highest polarizability at DC, ranging from 0.21 to 0.25 mm and decaying exponentially with frequency. Inhibitory neurons displayed membrane resonance in the 5-15 Hz range with lower polarizability, although bipolar cells had higher polarizability. Layer 5 PC demonstrated the highest entrainment close to 10 Hz, which decayed with frequency. In contrast, inhibitory neurons entrainment increased with frequency, reaching level akin to PC. Results from simplified models could replicate the phase preferences, while amplitudes tend to follow opposite trends in PC. Conclusion: tACS-induced membrane polarization is frequency-dependent, revealing observable resonance behavior. This finding motivates further experimental studies of cell-specific frequency-dependent membrane responses to weak electric stimuli. Whilst optimal phase entrainment of sustained activity is achieved in PC when tACS frequency matches the activity, inhibitory neurons tend to be entrained at higher frequencies. Consequently, this presents the potential for precise, cell-specific targeting.
Synergistic Effects of Sulopenem in Combination with Cefuroxime or Durlobactam againstMycobacterium abscessus
Authors: Dousa Khalid M. , Shin Eunjeong , Kurz Sebastian G. , Plummer Mark , Nantongo Mary , Bethel Christopher R. , Taracila Magdalena A. , Nguyen David C. , Kreiswirth Barry N. , Daley Charles L. , Remy Kenneth E. , Holland Steven M. , Bonomo Robert A.
Published: December 2023

Mycobacterium abscessus(Mab) affects patients with immunosuppression, Cystic Fibrosis (CF), or underlying structural lung diseases. Additionally,Mabposes clinical challenges due to its resistance to multiple antibiotics. Herein, we investigated the synergistic effect of dual β-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with a β-lactamase inhibitors [BLI; avibactam (AVI) or durlobactam (DUR)]. The sulopenem-CXM combination yielded low minimum inhibitory concentration MIC values for 54 clinicalMabisolates and ATCC19977 (MIC50and MIC90≤ 0.25 μg/mL). Similar synergistic effects were observed in time-kill studies conducted at concentrations achievable in clinical settings. Sulopenem-CXM outperformed monotherapy, yielding ∼1.5 Log10CFU/mL reduction during 10 days. Addition of BLIs enhanced this antibacterial effect, resulting in additional reduction of CFUs (∼3 Log10for sulopenem-CXM and AVI and ∼4 Log10for sulopenem-DUR). Exploration of the potential mechanisms of the synergy focused on their interactions with L,D-transpeptidases (LDTs; LDTMab1–LDTMab4), Penicillin-Binding-Protein B (PBP-B), and D,D-Carboxypeptidase (DDC). Acyl complexes identified via mass spectrometry analysis, demonstrated the binding of sulopenem with LdtMab2-LdtMab4, DDC, and PBP B, and CXM with LdtMab2and PBP-B. Molecular docking suggested formation of a covalent adduct between sulopenem and LdtMab2after the nucleophilic attack of the cysteine residue at the β-lactam carbonyl carbon, leading to the cleavage of the β-lactam ring, and the establishment of a thioester bond linking the LdtMab2with sulopenem. In conclusion, we demonstrated the biochemical basis of the synergy of sulopenem-CXM with or without BLI. These findings potentially broaden selection of oral therapeutic agents to combatMab.
Comparative genomics and the salivary transcriptome of the redbanded stink bug shed light on its high damage potential to soybean
Authors: Walt Hunter K. , King Jonas G. , Towles Tyler B. , Ahn Seung-Joon , Hoffmann Federico G.
Published: December 2023

The redbanded stink bug,Piezodorus guildinii(Westwood) (Hemiptera: Pentatomidae), is a significant soybean pest in the Americas, inflicting more physical damage on soybean than other native stink bugs. Studies suggest that its heightened impact is attributed to the aggressive digestive properties of its saliva. Despite its agricultural importance, the factors driving its greater ability to degrade plant tissues have remained unexplored in a genomic evolutionary context. In this study, we hypothesized that lineage-specific gene family expansions have increased the dosage of digestive genes expressed in the salivary glands. To investigate this, we annotated a previously published genome assembly of the redbanded stink bug and performed a comparative genomic analysis on 11 hemipteran species and reconstructed patterns of gene duplication, gain, and loss in the redbanded stink bug. We also performed RNA-seq on the redbanded stink bug’s salivary tissues, along with the rest of the body without salivary glands. We identified hundreds of differentially expressed salivary genes, including a subset lost in other stink bug lineages but retained and expressed in the redbanded stink bug’s salivary glands. These genes were significantly enriched with protein families involved in proteolysis, potentially explaining the redbanded stink bug’s heightened damage to soybeans. Contrary to our hypothesis, we found no support for an increased dosage of digestive genes in the salivary glands of the redbanded stink bug. Nonetheless, these results provide insight into the evolution of this important crop pest, establishing a link between its genomic history and its agriculturally important physiology.

SIGNIFICANCE STATEMENT

The redbanded stink bug, an important soybean pest in the Americas, inflicts greater damage to soybean due to higher salivary digestion. We employed comparative genomics and analyses of the salivary transcriptome to explore this and found that the differential retention of ancestral salivary genes may explain this phenomenon better than gene gains or duplications in the redbanded stink bug genome. We identify a distinct set of genes in the salivary gland that were differentially retained and expressed in the redbanded stink bug lineage, demonstrating enrichment in proteolytic function. This discovery offers a potential explanation for the redbanded stink bug’s elevated damage to soybean crops.
Targetable leukemia dependency on noncanonical PI3Kγ signaling
Authors: Luo Qingyu , Raulston Evangeline G. , Prado Miguel A. , Wu Xiaowei , Gritsman Kira , Yan Kezhi , Booth Christopher A. G. , Xu Ran , van Galen Peter , Doench John G. , Shimony Shai , Long Henry W. , Neuberg Donna S. , Paulo Joao A. , Lane Andrew A.
Published: December 2023

Phosphoinositide 3-kinase gamma (PI3Kγ) is implicated as a target to repolarize tumor-associated macrophages and promote anti-tumor immune responses in solid cancers. However, cancer cell-intrinsic roles of PI3Kγ are unclear. Here, by integrating unbiased genome-wide CRISPR interference screening with functional analyses across acute leukemias, we define a selective dependency on the PI3Kγ complex in a high-risk subset that includes myeloid, lymphoid, and dendritic lineages. This dependency is characterized by innate inflammatory signaling and activation of phosphoinositide 3-kinase regulatory subunit 5 (PIK3R5), which encodes a regulatory subunit of PI3Kγ and stabilizes the active enzymatic complex. Mechanistically, we identify p21 (RAC1) activated kinase 1 (PAK1) as a noncanonical substrate of PI3Kγ that mediates this cell-intrinsic dependency independently of Akt kinase. PI3Kγ inhibition dephosphorylates PAK1, activates a transcriptional network of NFκB-related tumor suppressor genes, and impairs mitochondrial oxidative phosphorylation. We find that treatment with the selective PI3Kγ inhibitor eganelisib is effective in leukemias with activatedPIK3R5, either at baseline or by exogenous inflammatory stimulation. Notably, the combination of eganelisib and cytarabine prolongs survival over either agent alone, even in patient-derived leukemia xenografts with low baseline PIK3R5 expression, as residual leukemia cells after cytarabine treatment have elevated G protein-coupled purinergic receptor activity and PAK1 phosphorylation. Taken together, our study reveals a targetable dependency on PI3Kγ/PAK1 signaling that is amenable to near-term evaluation in patients with acute leukemia.
A Boundary Element Method of Bidomain Modeling for Predicting Cellular Responses to Electromagnetic Fields
Authors: Czerwonky David M. , Aberra Aman S. , Gomez Luis J.
Published: December 2023

Objective

Commonly used cable equation-based approaches for determining the effects of electromagnetic fields on excitable cells make several simplifying assumptions that could limit their predictive power. Bidomain or “whole” finite element methods have been developed to fully couple cells and electric fields for more realistic neuron modeling. Here, we introduce a novel bidomain integral equation designed for determining the full electromagnetic coupling between stimulation devices and the intracellular, membrane, and extracellular regions of neurons.

Methods

Our proposed boundary element formulation offers a solution to an integral equation that connects the device, tissue inhomogeneity, and cell membrane-induced E-fields. We solve this integral equation using first-order nodal elements and an unconditionally stable Crank-Nicholson time-stepping scheme. To validate and demonstrate our approach, we simulated cylindrical Hodgkin-Huxley axons and spherical cells in multiple brain stimulation scenarios.

Main Results

Comparison studies show that a boundary element approach produces accurate results for both electric and magnetic stimulation. Unlike bidomain finite element methods, the bidomain boundary element method does not require volume meshes containing features at multiple scales. As a result, modeling cells, or tightly packed populations of cells, with microscale features embedded in a macroscale head model, is made computationally tractable, and the relative placement of devices and cells can be varied without the need to generate a new mesh.

Significance

Device-induced electromagnetic fields are commonly used to modulate brain activity for research and therapeutic applications. Bidomain solvers allow for the full incorporation of realistic cell geometries, device E-fields, and neuron populations. Thus, multi-cell studies of advanced neuronal mechanisms would greatly benefit from the development of fast-bidomain solvers to ensure scalability and the practical execution of neural network simulations with realistic neuron morphologies.
Plant infection by the necrotrophic fungusBotrytisrequires actin-dependent generation of high invasive turgor pressure
Authors: Müller Tobias , Bronkhorst Jochem , Müller Jonas , Safari Nassim , Hahn Matthias , Sprakel Joris , Scheuring David
Published: December 2023

The devastating pathogenBotrytis cinereainfects a broad spectrum of host plants, causing great socio-economic losses. The necrotrophic fungus rapidly kills plant cells, nourishing their walls and cellular contents. To this end, necrotrophs secretes a cocktail of cell wall degrading enzymes, phytotoxic proteins and metabolites. Additionally, many fungi produce specialized invasion organs that generate high invasive pressures to force their way into the plant cell. However, for most necrotrophs, includingBotrytis, the biomechanics of penetration and its contribution to virulence are poorly understood. Here we use a combination of quantitative micromechanical imaging and CRISPR-Cas guided mutagenesis to show thatBotrytisuses substantial invasive pressure, in combination with strong surface adherence, for penetration. We found that the fungus establishes a unique mechanical geometry of penetration that develops over time during penetration events, and which is actin cytoskeleton dependent. Furthermore, interference of force generation by blocking actin polymerization was found to decreaseBotrytisvirulence, indicating that also for necrotrophs, mechanical pressure is important in host colonization. Our results demonstrate for the first time mechanistically how a necrotrophic fungus such asBotrytisemploys this “brute force” approach, in addition to the secretion of lytic proteins and phytotoxic metabolites, to overcome plant host resistance.
Hybrid adaptation is hampered by Haldane’s sieve
Authors: Bautista Carla , Gagnon-Arsenault Isabelle , Utrobina Mariia , Fijarczyk Anna , Bendixsen Devin P. , Stelkens Rike , Landry Christian R.
Published: December 2023

Hybrids between species exhibit plastic genomic architectures that foster phenotypic diversity. Their genomic instability also incurs costs, potentially limiting adaptation. When challenged to evolve in an environment containing a UV mimetic drug, yeast hybrids have reduced adaptation rates compared to parents. We hypothesized that this reduction could result from a faster accumulation of genomic changes, but we found no such association. Alternatively, we proposed that hybrids might lack access to adaptive mutations occurring in the parents, yet, we identified mutations in the same genes (PDR1 and YRR1), suggesting similar molecular adaptation mechanisms. However, mutations in these genes tended to be homozygous in the parents but heterozygous in the hybrids. We hypothesized that a lower rate of loss of heterozygosity (LOH) in hybrids could limit fitness gain. Using genome editing, we demonstrated that mutations display incomplete dominance, requiring homozygosity to show full impact and to circumvent Haldane’s sieve, which favors the fixation of dominant mutations. We used frozen ‘fossils’ to track genotype frequency dynamics and confirmed that LOH occurs at a slower pace in hybrids than in parents. Together, these findings show that Haldane’s sieve slows down adaptation in hybrids, revealing an intrinsic constraint of hybrid genomic architecture that can limit the role of hybridization in adaptive evolution.
Powdery mildew infection induces a non-canonical route to storage lipid formation at the expense of host thylakoid lipids to fuel its spore production
Authors: Jaenisch J. , Xue H. , Schläpfer J. , McGarrigle E.R. , Louie K. , Northen T.R. , Wildermuth M.C.
Published: December 2023

Powdery mildews are obligate biotrophic fungi that manipulate plant metabolism to supply lipids, particularly during fungal asexual reproduction when fungal lipid demand is extensive. The mechanism for host response to fungal lipid demand has not been resolved. We found storage lipids, triacylglycerols (TAGs), increase by 3.5-fold in powdery mildew-infected tissue. In addition, lipid bodies, not observable in uninfected mature leaves, are present in both cytosol and chloroplasts at the infection site. This is concurrent with decreased thylakoid membrane lipids and thylakoid disassembly. Together, these findings indicate that the powdery mildew induces localized thylakoid membrane degradation to promote storage lipid formation. Genetic analyses show the canonical ER pathway for TAG synthesis does not support powdery mildew spore production. Instead, Arabidopsis DIACYLGLYCEROL ACYLTRANSFERASE 3 (DGAT3), shown to be chloroplast-localized and to be largely responsible for powdery mildew-induced chloroplast TAGs, promotes fungal asexual reproduction. Powdery mildew-induced leaf TAGs are enriched in thylakoid associated fatty acids, which are also present in the produced spores. This research provides new insights on obligate biotrophy and plant lipid metabolism plasticity and function. Furthermore, by understanding how photosynthetically active leaves can be converted into TAG producers, more sustainable and environmentally benign plant oil production could be facilitated.
Imaging the voltage of neurons distributed across entire brains of larval zebrafish
Authors: Wang Zeguan , Zhang Jie , Symvoulidis Panagiotis , Guo Wei , Zhang Lige , Wilson Matthew A. , Boyden Edward S.
Published: December 2023

Neurons interact in networks distributed throughout the brain. Although much effort has focused on whole-brain calcium imaging, recent advances in genetically encoded voltage indicators (GEVIs) raise the possibility of imaging voltage of neurons distributed across brains. To achieve this, a microscope must image at high volumetric rate and signal-to-noise ratio. We present a remote scanning light-sheet microscope capable of imaging GEVI-expressing neurons distributed throughout entire brains of larval zebrafish at a volumetric rate of 200.8 Hz. We measured voltage of ∼1/3 of the neurons of the brain, distributed throughout. We observed that neurons firing at different times during a sequence were located at different brain locations, for sequences elicited by a visual stimulus, which mapped onto locations throughout the optic tectum, as well as during stimulus-independent bursts, which mapped onto locations in the cerebellum and medulla. Whole-brain voltage imaging may open up frontiers in the fundamental operation of neural systems.
The evaluation of grey relative incidence
Authors: Nowak Marcin , Pawłowska-Nowak Marta , Kokocińska Małgorzata , Kułyk Piotr
Published: December 2023

Purpose

With the use of the grey incidence analysis (GIA), indicators such as the absolute degree of grey incidence (εij), relative degree of grey incidence (rij) or synthetic degree of grey incidence (ρij) are calculated. However, it seems that some assumptions made to calculate them are arguable, which may also have a material impact on the reliability of test results. In this paper, the authors analyse one of the indicators of the GIA, namely the relative degree of grey incidence. The aim of the article was to verify the hypothesis: in determining the relative degree of grey incidence, the method of standardisation of elements in a series significantly affects the test results.

Design/methodology/approach

To achieve the purpose of the article, the authors used the numerical simulation method and the logical analysis method (in order to draw conclusions from our tests).

Findings

It turned out that the applied method of standardising elements in series when calculating the relative degree of grey incidence significantly affects the test results. Moreover, the manner of standardisation used in the original method (which involves dividing all elements by the first element) is not the best. Much more reliable results are obtained by a standardisation that involves dividing all elements by their arithmetic mean.

Research limitations/implications

Limitations of the conducted evaluation involve in particular the limited scope of inference. This is since the obtained results referred to only one of the indicators classified into the GIA.

Originality/value

In this article, the authors have evaluated the model of GIA in which the relative degree of grey incidence is determined. As a result of the research, the authors have proposed a recommendation regarding a change in the method of standardising variables, which will contribute to obtaining more reliable results in relational tests using the grey system theory.
Another look at data challenges in property valuation practice: a case of Lagos property market
Authors: Oladokun Sunday Olarinre , Mooya Manya Mainza
Published: December 2023

Purpose

Challenges of property data in developing markets have been reported by several authors. However, a deep understanding of the actual nature of this phenomenon in developing markets is largely lacking as in-depth studies into the actual nature of data challenge in such markets are scarce in literature. Specifically, the available literature lacks clarity about the actual nature of data challenges that developing markets pose to valuers and how this affects valuation practice. This study provides this understanding with focus on the Lagos property market.

Design/methodology/approach

This study utilises a qualitative research approach. A total of 24 valuers were selected using snowballing sampling technique, and in-depth semi-structured interviews were conducted. Data collected were analysed using thematic analysis with the aid of NVivo 12 software.

Findings

The study finds that the main data-related challenge in the Lagos property market is the lack of database of market property transactions and not the lack or absence of transaction data as it has been emphasised in previous studies. Other data-related challenges identified include weak property rights institution with attendant transaction costs, underhand dealings among professionals, undocumented charges, undisclosed information, scarcity of data relating to specialised assets and limited access to the subject property and required documents during valuation. Also, the study unbundles the factors responsible for these challenges and how they affect valuation practice.

Practical implications

The study has implication for practice in the sense that the deeper knowledge of data challenges could provide insight into strategy to tackle the challenges.

Originality/value

This study contributes to the body of knowledge by offering a fresh and in-depth perspective to the issue of data challenges in developing markets and how the peculiar nature of the real estate market affects the nature of data challenges. The qualitative approach adopted in this study allowed for a deep enquiry into the phenomenon and resulted into an extended insight into the peculiar nature of data challenges in a typical developing property market.
Sociodemographic drivers and interconnected energy-saving practices: insights from Ecuador's household sector
Authors: Zambrano-Monserrate Manuel A. , Ruano Maria Alejandra
Published: December 2023

Purpose

The escalating levels of greenhouse gas emissions have become a growing global concern, with household energy consumption emerging as a significant contributor. To develop effective public policies, it is crucial to understand the energy-saving behavior of households. This study delves into the determinants of energy-saving practices in a developing country.

Design/methodology/approach

The authors chose a multivariate probit model, as it allowed to look after possible correlations among seven energy-saving practices within households.

Findings

The findings underscore the significant influence of sociodemographic variables, such as gender, civil status, income and education, on energy-saving practices. Furthermore, the authors discovered that households where the head actively volunteers in social organizations are more likely to adopt energy-saving behaviors. Additionally, internet access positively contributes to pro-environmental behavior. This research reveals that certain energy-saving practices are interconnected, acting as complements or substitutes.

Research limitations/implications

Recommendations for public policy include prioritizing education in rural areas to boost energy-saving practices, improving internet access in nonurban regions and promoting citizen involvement in social organizations to enhance environmental awareness and encourage energy-saving behavior. The authors contribute to literature evidencing that certain energy-saving practices are not independent of each other, they are rather complementary and, in some cases, substitutes.

Practical implications

Recommendations for public policy include prioritizing education in rural areas to boost energy-saving practices, improving Internet access in nonurban regions and promoting citizen involvement in social organizations to enhance environmental awareness and encourage energy-saving behavior.

Originality/value

Previous studies have overlooked these interdependencies, highlighting the necessity of a system of equations to yield more efficient estimates by considering correlations between error terms.
Ultrastructural characteristics and morphological relationships of cardiomyocytes and telocytes in the myocardium of the bullfrog (Rana catesbeiana)
Authors: Wang Zifan , Xu Yizhen , Huang Ling , Zhao Jiancheng , Ye Yaqiong , Liu Canying , Wang Bingyun , Zhao Haiquan , Zhang Hui
Published: December 2023

Telocytes (TCs) are distinctive interstitial cells due to their characteristic structures and heterogeneity. They are suggested to participate in tissue repair/regeneration. TCs have been identified in many organs of various mammals. However, data on TCs in lower animals are still very limited. In this work, TCs were identified in the myocardium of the bullfrog (Rana catesbeiana) by light and transmission electron microscopy (TEM). The structural relationships between TCs and neighbouring cell types were measured using the ImageJ (FiJi) morphometric software. TCs with slender Tps (telepodes) were located around cardiomyocytes (CMC). TEM revealed TCs with long Tps in the stroma between CMC. The homocellular tight junctions were observed between the Tps. The Tps were also very close to the neighbouring CMC. The distance between Tps and CMC was 0.15 ± 0.08 μm. Notably, Tps were observed to adhere to the periphery of the satellite cells. The Tps and the satellite cells established heterocellular structural connections by tight junctions. Additionally, Tps were frequently observed in close proximity to mast cells (MCs). The distance between the Tps and the MCs was 0.19 ± 0.09 μm. These results confirmed that TCs are present in the myocardium of the bullfrog, and that TCs established structural relationships with neighbouring cell types, including satellite cells and MCs. These findings provide the anatomical evidence to support the note that TCs are involved in tissue regeneration.
The changing clinical presentation of COVID‐19 in children during the course of the pandemic
Authors: Wurm Juliane , Uka Anita , Bernet Vera , Buettcher Michael , Giannoni Eric , Kottanattu Lisa , Schöbi Nina , Zemmouri Abdelaziz , Ritz Nicole , Zimmermann Petra ,   Swiss Paediatric Surveillance Unit (SPSU)
Published: December 2023

Aim

To investigate the evolution of clinical symptoms of COVID‐19 in children throughout the pandemic.

Methods

In this national prospective surveillance study, symptoms in children hospitalised with COVID‐19 were collected from all paediatric hospitals in Switzerland between March 2020 and March 2023. Data was analysed across four time periods, according to the predominantly circulating SARS‐CoV‐2 variant: T1 (wild‐type), T2 (Alpha), T3 (Delta) and T4 (Omicron), as well as by age group.

Results

The study included 1323 children. The proportion of children admitted to an intensive care unit remained stable throughout the pandemic. However, the pattern and frequency of clinical manifestations changed over time. Respiratory symptoms were less prevalent during T1 (wild‐type), fever during T2 (Alpha) and rash during T4 (Omicron). In contrast, fever and neurological symptoms were more prevalent during T4 (Omicron). Newly described symptoms during T4 (Omicron) included conjunctivitis, laryngotracheitis and seizures. Fever was more prevalent among neonates and infants whereas respiratory symptoms were more common among infants. Gastrointestinal symptoms were more frequent among toddlers, while both toddlers and school‐aged children presented with neurological symptoms more often than other age groups.

Conclusion

Continuous surveillance is required to detect changes in manifestations and there by be prepared for the optimal management of complications in children with COVID‐19.
Oral administration of Brevibacterium linens from washed cheese increases the proportions of short‐chain fatty acid‐producing bacteria and lactobacilli in the gut microbiota of mice
Authors: Murakami Aito , Toyomoto Koharu , Namai Fu , Sato Takashi , Fujii Tadashi , Tochio Takumi , Shimosato Takeshi
Published: December 2023

Brevibacterium linens (B. linens) is a dairy microorganism used in the production of washed cheese. However, there has been little research on B. linens, especially regarding its effects in vivo. Herein, we report the morphological characteristics of B. linens, such as its two‐phase growth and V‐ and Y‐shaped bodies. We also report that oral administration of B. linens increased the diversity of the gut microbiota and promoted the growth of lactobacilli and short‐chain fatty acid‐producing bacteria, such as Lachnospiraceae and Muribaculaceae. These findings suggest that the ingestion of B. linens may have beneficial effects in humans and animals.
Rapid functional but slow species diversity recovery of steppe vegetation on former arable fields in southern Ukraine
Authors: Dembicz Iwona , Zachwatowicz Maria , Moysiyenko Ivan , Shapoval Viktor , Smreczak Bożena , Zagorodniuk Natalia , Davydova Anastasia , Vynokurov Denys , Seiler Hallie , Sudnik‐Wójcikowska Barbara
Published: December 2023

Questions

European steppes are among the most threatened ecosystems in the Palaearctic region, mainly because of conversion to arable land. Abandonment may allow for the passive recovery of steppes. We made use of an exceptional old‐field succession chronosequence of nearly 100 years to answer the following questions: (a) Are the plant species composition, species richness and functional characteristics typical of virgin grass steppes able to self‐restore during ca. 100 years after abandonment? (b) Do the rates of recovery of the above vegetation characteristics differ over the studied chronosequence? (c) Do topsoil carbon and nitrogen content change over the succession chronosequence, leading to concentrations similar to that of virgin steppes?

Location

Southern Ukraine.

Methods

We sampled vegetation and soil in a virgin grass steppe and in old fields abandoned for 6, 15, 31, 50 and ca. 97 years. We subjected the composition data to multivariate analysis. To test whether species richness, functional and soil characteristics of the old fields diverge from those of the virgin steppe, we used one‐way analysis of variance with Tukey's honestly significant difference (HSD) statistic to create 90% confidence intervals.

Results

The vegetation composition of the three most recently abandoned old fields differed significantly from that of the virgin steppe. The species richness of vascular plants was lower in old fields than in the virgin steppe. The share of steppe habitat specialists was similar to the virgin steppe only in the field abandoned for ca. 97 years. Functional characteristics were significantly different from the virgin steppe only in the most recently abandoned old field. Contents of Corg and Ntot in fields abandoned for ≤50 years were lower compared with the virgin steppe.

Conclusions

The functional characteristics of steppe vegetation seem to recover much faster than its biodiversity. However, based on our results, 100 years can be enough time for the spontaneous re‐establishment of typical steppe vegetation.
Plasma 6β‐hydroxycortisol to cortisol ratio as a less invasive cytochrome P450 3A phenotyping method
Authors: Hirano Ryohei , Yokokawa Akitomo , Furihata Tomomi , Shibasaki Hiromi
Published: December 2023

Aim

A less invasive evaluation method of cytochrome P450 3A (CYP3A) activity provides an important tool for personalized medicine. We aimed to clarify the usefulness of the plasma 6β‐hydroxycortisol to cortisol concentration (6β‐OHF/F) ratio as a minimally invasive CYP3A phenotyping method.

Methods

Plasma 6β‐OHF and cortisol concentrations were measured via liquid chromatography/tandem mass spectrometry. The plasma 6β‐OHF/F ratio was compared with 6β‐hydroxylation clearance of endogenous cortisol (CLm(6β); which we previously developed as an index of CYP3A activity) before, during and after oral contraceptive administration in 3 healthy women. The plasma 6β‐OHF/F ratio was observed during oral clarithromycin administration. The plasma 6β‐OHF/F ratio was also measured in 39 healthy participants.

Results

The plasma 6β‐OHF/F ratio in 3 healthy women on Day 21 of starting oral contraceptive administration decreased by 39, 49 and 61% compared with Day 0. These values were similar to CLm(6β) values (43, 54 and 59%, respectively). Plasma 6β‐OHF/F ratio and CLm(6β) exhibited a good correlation (r = .9053). The 6β‐OHF/F ratio decreased from 0.00921 to 0.00577 only 3 h following clarithromycin administration. The plasma 6β‐OHF/F ratio ranged 0.00565–0.01556 in 39 healthy participants.

Conclusion

Based on its close relationship with CLm(6β) and its decrease upon inhibition by clarithromycin, the plasma 6β‐OHF/F ratio serves as an index of CYP3A activity. Using this minimally invasive index, we can identify patients with extremely low CYP3A activity before treatment initiation and optimize the initial drug dose, thereby mitigating the risk of severe adverse reactions.
Navigating corporate philanthropy in the digital world: The normative effect of Entrepreneurs' social media usage
Authors: Chen Jiawen , Ke Xiaolian , Liu Linlin
Published: December 2023

This paper investigates how entrepreneurs' social media usage affects corporate philanthropy. Departing from the extant literature, which focuses on the instrumental role of social media, we draw upon the normative perspective of stewardship theory and propose that entrepreneurs' social media usage promotes their ethical and prosocial motivation for corporate philanthropy. In particular, we theorize that entrepreneurs' social media usage enhances their self‐perceived status and philanthropic identification, thus affecting corporate philanthropy. Our analysis of a sample of Chinese ventures provides empirical support for the mediating effects of self‐perceived status and philanthropic identification on the relationship between entrepreneurs' social media usage and the philanthropic propensity and intensity of their ventures. Our study has implications for the role of social media in promoting corporate philanthropy and contributes to the literature on entrepreneurship and corporate philanthropy.
Multifaceted approach toward mapping out the anticancer properties of small molecules via in vitro evaluation on melanoma and nonmelanoma skin cancer cells, and in silico target fishing
Authors: Boateng Samuel T. , Roy Tithi , Agbo Mercy E. , Mahmud Md Ashiq , Banang‐Mbeumi Sergette , Chamcheu Roxane‐Cherille N. , Yadav Rajesh K. , Bramwell Marion , Pham Long K. , Dang Danny D. , Jackson Keith E. , Nagalo Bolni Marius , Hill Ronald A. , Efimova Tatiana , Fotie Jean , Chamcheu Jean Christopher
Published: December 2023

Melanoma and nonmelanoma skin cancers are among the most prevalent and most lethal forms of skin cancers. To identify new lead compounds with potential anticancer properties for further optimization, in vitro assays combined with in‐silico target fishing and docking have been used to identify and further map out the antiproliferative and potential mode of action of molecules from a small library of compounds previously prepared in our laboratory. From screening these compounds in vitro against A375, SK‐MEL‐28, A431, and SCC‐12 skin cancer cell lines, 35 displayed antiproliferative activities at the micromolar level, with the majority being primarily potent against the A431 and SCC‐12 squamous carcinoma cell lines. The most active compounds 11 (A431: IC50 = 5.0 μM, SCC‐12: IC50 = 2.9 μM, SKMEL‐28: IC50 = 4.9 μM, A375: IC50 = 6.7 μM) and 13 (A431: IC50 = 5.0 μM, SCC‐12: IC50 = 3.3 μM, SKMEL‐28: IC50 = 13.8 μM, A375: IC50 = 17.1 μM), significantly and dose‐dependently induced apoptosis of SCC‐12 and SK‐MEL‐28 cells, as evidenced by the suppression of Bcl‐2 and upregulation of Bax, cleaved caspase‐3, caspase‐9, and PARP protein expression levels. Both agents significantly reduced scratch wound healing, colony formation, and expression levels of deregulated cancer molecular targets including RSK/Akt/ERK1/2 and S6K1. In silico target prediction and docking studies using the SwissTargetPrediction web‐based tool suggested that CDK8, CLK4, nuclear receptor ROR, tyrosine protein‐kinase Fyn/LCK, ROCK1/2, and PARP, all of which are dysregulated in skin cancers, might be prospective targets for the two most active compounds. Further validation of these targets by western blot analyses, revealed that ROCK/Fyn and its associated Hedgehog (Hh) pathways were downregulated or modulated by the two lead compounds. In aggregate, these results provide a strong framework for further validation of the observed activities and the development of a more comprehensive structure–activity relationship through the preparation and biological evaluation of analogs.
A metascience investigation of inclusive, open, and reproducible science practices in research posters at the 2021 SRCD biennial meeting
Authors: Kim Matthew H. , Buford Kristen , Ellis Alexa , Davis‐Kean Pamela E. , Antony Chellam , Braun Claire , Hurst Tabetha , Todd Julia
Published: December 2023

Over the past decade, there has been a growing appreciation of metascience issues in psychological science. Using data collected from 2615 posters presented at the 2021 biennial meeting of the Society for Research in Child Development, this article examines the use of transparent research practices to increase rigor and reproducibility as well as generalizability through greater inclusivity of diverse samples. Research presented through poster presentations was heavily skewed toward quantitative studies featuring American researchers using Western hemisphere samples. Sharing of data/materials, preregistrations, and replications were uncommon. During a time when governments are increasingly requiring more open practices and access, this research provides an important baseline by which developmental science can benchmark progress toward the goals of greater inclusivity and openness.
‘We live here and play here, we should have a say’: An exploration of children's perceptions of place‐making in the Market community, Belfast
Authors: McAteer Benedict , Loudon Emma , Higgins Kathryn
Published: December 2023

Children learn through interaction with their surroundings, meaning that their experiences of place directly contribute to their personal development. Despite this, the needs of the youth are rarely factored into development plans. This is a major obstacle to the sustainable and inclusive development of places. Examining potential pathways to correct this issue, this paper presents the findings of research conducted with young people from the Market area of Belfast. The research engaged with two groups (n = 11) in a participatory investigation of how young people engage with the built environment. Using several participatory methods, including narrative walkabouts, mapping exercises and semi‐structured group interviews, the children engaged as co‐researchers. We link to idea of ‘third places’ to frame our analysis, demonstrating how children in the Market community have strong opinions of how space is, and should be, designed and managed. We reveal interesting dynamics regarding the children's perceived exclusion from the city centre and concerns about how poor planning is harming their community's public health. We conclude by reflecting upon some of the children's proposed solutions, as well as by presenting two outcomes of our study that hint at the potential future role of young people in co‐designing the built environment.
TEMPI syndrome: A clinical, light‐microscopic and phenotypic evaluation with review of the literature
Authors: Kalomeris Taylor A. , Grossman Marc E. , Tepler Jeffrey , Magro Cynthia M.
Published: December 2023

Background and objectives

TEMPI (telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonaryshunting) syndrome is a rare multisystemic disease classified as a monoclonal gammopathy of cutaneous significance. The pathogenesis and etiology of TEMPIare not well known because of the rarity of this disorder. Although telangiectasias are the hallmark of this syndrome, skin biopsies are rarely performed. We aim to further characterize TEMPI syndrome through the evaluationof a skin biopsy.

Methods

We reviewed the histopathology and immunophenotypic profile of a skin biopsy from a 53‐year‐oldwoman diagnosed with TEMPI syndrome. Other components of her syndromic complex included an IgA myeloma, elevated vascular endothelial growth factor (VEGF), and erythrocytosis.

Results

A biopsy showed prominent vascular ectasia with some degree of microvascular basement membranezone thickening. Our patient had a reduction in neoplastic plasma cell burdenand clearing of her telangiectasias following myeloma directed treatment.

Conclusions

TEMPI can beviewed as a reactive vascular paraneoplastic syndrome in the setting of a plasma cell dyscrasia. Elaboration of VEGF from neoplastic plasma cells is likely pathogenetically implicated and appears to be a common link that explains other vascular lesions associated with monoclonal gammopathy syndromes.
The effect of instructor communication on affective learning in a supply chain management course
Authors: Johnson Laquanda Leaven , Park Arim , Kelly Stephanie
Published: December 2023

The purpose of this study is to understand how instructor clarity and computer‐mediated behaviors influence students’ affective learning and technology self‐efficacy in online supply chain management (SCM) courses, which show how the instructor–student relationship affects online learning experiences. Data were collected through an online questionnaire using the Prolific human subject's pool. The data supported a model in which instructors’ clarity and computer‐mediated immediate behaviors indirectly influenced students’ technology self‐efficacy and affect for the course through the mediation of perceived immediacy. Affect for the instructor did not fit into the final model. The findings in this study help SCM instructors navigate the pedagogical pivot that may be required for the next unexpected event (pandemic, etc.) without compromising student learning goals.