bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candida albicanscells lacking AP-2 have defective hyphae and are avirulent despite increased host uptake and intracellular proliferation in macrophages
Authors: Christou Stella , Ayscough Kathryn R. , Johnston Simon A. 
Published: August 2023

AbstractCandida albicansis a commensal microbe and opportunistic human pathogen. The yeast can be recognised and taken up by macrophages via interactions with its cell wall, a complex polysaccharide structure containing several components that are specifically recognised by immune cell receptors. Following uptakeCandidacan respond in the host environment by switching from a yeast to hyphal morphology which facilitates escape from macrophages and allows subsequent invasion of host tissues. Disruption ofCandida’s ability to form hyphae results in reduced virulence and fitness for survival in the host environment.Candida albicanscells lacking AP-2, an endocytic adaptor complex, have increased cell wall chitin and morphologically defective hyphaein vitro. Previous studies have correlated increased chitin with decreased recognition by macrophages, possibly due to masking of cell wall beta-glucan which is recognised by dectin receptors. Despite the cell wall changes in the mutant strain there was an unexpected increased uptake of the mutant. Increased chitin did not reduce phagocytosis and additional uptake was not due to compensatory elevated exposure of beta-glucan, highlighting the importance of cell wall components beyond chitin and glucan for macrophage engagement and uptake. Furthermore, theapm4mutant exhibited parasitism of macrophages, surviving and proliferating within the phagosome, a phenotype that was then replicated with a well-characterised yeast locked mutant.Finally, the combined phenotype of reduced hyphal formation but continued proliferation resulted in reduced virulence despite an equivalent burden of infection to a wild-typeCandidainfection, as determined using a zebrafish larval model of candidiasis.
DsrMKJOP is the terminal reductase complex in anaerobic sulfate respiration
Authors: Barbosa Ana C. C. , Venceslau Sofia S. , Pereira Inês A. C. 
Published: August 2023

ABSTRACTMicrobial dissimilatory sulfate reduction is a key process in the Earth biogeochemical sulfur cycle. In spite of its importance to the sulfur and carbon cycles, industrial processes and human health, it is still not clear how reduction of sulfate to sulfide is coupled to energy conservation. A central step in the pathway is the reduction of sulfite by the DsrAB dissimilatory sulfite reductase, which leads to the production of a DsrC-trisulfide. A membrane-bound complex, DsrMKJOP, is present in most organisms that have DsrAB and DsrC, and its involvement in energy conservation has been inferred from sequence analysis, but its precise function was so far not determined. Here, we present studies revealing that the DsrMKJOP complex of the sulfate reducerArchaeoglobus fulgidusworks as a menadiol:DsrC-trisulfide oxidoreductase. Our results reveal a close interaction between the DsrC-trisulfide and the DsrMKJOP complex and show that electrons from the quinone pool reduce consecutively the DsrM hemesb, the DsrK noncubane [4Fe-4S]3+/2+catalytic center, and finally the DsrC-trisulfide with concomitant release of sulfide. These results clarify the role of this widespread respiratory membrane complex and indicate that DsrMKJOP will provide the missing link to energy conservation by generating aproton motive forceacross the membrane in the last step of dissimilatory sulfate reduction.Significance StatementDissimilatory sulfate reduction (DSR) is a vital microbial process in anoxic environments, namely in sulfate-rich marine sediments that harbor a vast microbial ecosystem. DSR drives the global biogeochemical sulfur cycle and is crucial in remineralization of organic matter on the seafloor. It also has huge environmental impact by preventing release of the greenhouse gas methane from these sediments, through its oxidation coupled to sulfate reduction. Despite its high ecological importance, it is still not clear how microorganisms derive energy to grow through DSR. Here, we disclose the physiological function of a widespread membrane complex in DSR, showing it acts as the terminal reductase in the respiratory chain and providing important insights into how sulfate/sulfite reduction is linked to energy conservation.
Ion-Concentration Gradients During Synaptic Input Increase the Voltage Depolarization in Dendritic Spines
Authors: Eberhardt Florian 
Published: August 2023

AbstractThe cable equation is key for understanding the electrical potential along dendrites or axons, but its application to dendritic spines remains limited. Their volume is extremely small so that moderate ionic currents suffice to alter ionic concentrations. The resulting chemical-potential gradients between dendrite and spine head lead to measurable electrical currents. The cable equation, however, considers electrical currents only as result of gradients in the electrical potential. The Poisson-Nernst-Planck (PNP) equations allow a more accurate description, as they include both types of currents. Previous PNP simulations predict a considerable change of ionic concentrations in spines during an excitatory postsynaptic potential (EPSP). However, solving PNP-equations is computationally expensive, limiting their applicability for complex structures.Here, we present a system of equations that generalizes the cable equation and considers both, electrical potentials and time-dependent concentrations of ion species with individual diffusion constants. Still, basic numerical algorithms can be employed to solve such systems. Based on simulations, we confirm that ion concentrations in dendritic spines are changing significantly during current injections that are comparable to synaptic events. Electrical currents reflecting ion diffusion through the spine neck increase voltage depolarizations in the spine head. Based on this effect, we identify a mechanism that affects the influx of Ca2+ in sequences of pre- and postsynaptic action potentials. Taken together, the diffusion of individual ion species need to be taken into account to accurately model electrical currents in dendritic spines. In the future the presented equations can be used to accurately integrate dendritic spines into multicompartment models to study synatptic integration.
Loss of zebrafishdcst2expression is not associated with muscle abnormalities
Authors: Allard-Chamard X. , Rodríguez E.C. , Brais B. , Armstrong G.A.B. 
Published: August 2023

AbstractIn this study we examined if the gene encoding Dendritic Cell-specific Six Transmembrane domain containing protein 2 (dcst2) plays a role in vertebrate muscle biology. Using the CRISPR/Cas9 mutagenic system we generated a 2 nucleotide deletion in exon 3 of the zebrafish orthologdcst2which resulted in a premature stop codon. Homozygous carriers of the mutation displayed reduced transcriptional expression ofdcst2suggesting that our mutation was indeed disrupting gene function. Mutantdcst2zebrafish developed normally to adulthood and displayed no differences in motor function using a free-swim and swim tunnel assays. Furthermore, histological examination of muscle cells revealed no differences in slow-twitch or fast-twitch muscle cell cross-sectional area in our mutants. We did observe thatdcst2-/-zebrafish were slightly heavier in weight and males were infertile. The data collected here, suggest thatdcst2does not play a role in zebrafish muscle cell biology.
A comprehensive workflow and its validation for simulating diffuse speckle statistics for optical blood flow measurements
Authors: Kobayashi Frisk Lisa , Verma Manish , Bešlija Faruk , Lin Chen-Hao P. , Patil Nishighanda , Chetia Sumana , Trobaugh Jason , Culver Joseph P. , Durduran Turgut 
Published: August 2023

AbstractDiffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (k) to measure deep blood flow. In order to design practical systems, parameters such as signal-to-noise ratio (SNR) and the effects of limited sampling of statistical quantities, should be considered. To that end, we have developed a method for simulating speckle contrast signals including effects of detector noise. The method was validated experimentally, and the simulations were used to study the effects of physical and experimental parameters on the accuracy and precision ofk. These results revealed that systematic detector effects resulted in decreased accuracy and precision ofkin the regime of low detected signals. The method can provide guidelines for the design and usage of SCOS and/or SCOT instruments.
Oxidative rearrangement of tryptophan to indole nitrile by a single diiron enzyme
Authors: Adak Sanjoy , Ye Naike , Calderone Logan A. , Schäfer Rebecca J. B. , Lukowski April L. , Pandelia Maria-Eirini , Drennan Catherine L. , Moore Bradley S. 
Published: August 2023

AbstractNitriles are uncommon in nature and are typically constructed from oximes via the oxidative decarboxylation of amino acid substrates or from the derivatization of carboxylic acids. Here we report a third strategy of nitrile biosynthesis featuring the cyanobacterial nitrile synthase AetD. During the biosynthesis of the ‘eagle-killing’ neurotoxin, aetokthonotoxin, AetD converts the alanyl side chain of 5,7-dibromo-L-tryptophan to a nitrile. Employing a combination of structural, biochemical, and biophysical techniques, we characterized AetD as a non-heme diiron enzyme that belongs to the emergingHeme Oxygenase-likeDiironOxidase and Oxygenase (HDO) superfamily. High-resolution crystal structures of AetD together with the identification of catalytically relevant products provide mechanistic insights into how AetD affords this unique transformation that we propose proceeds via an aziridine intermediate. Our work presents a new paradigm for nitrile biogenesis and portrays a substrate binding and metallocofactor assembly mechanism that may be shared among other HDO enzymes.
Seeking voluntary passive movement in flies is play-like behavior
Authors: Triphan Tilman , Huetteroth Wolf 
Published: August 2023

AbstractPlay-like behaviour (PLB) is pervasive across the animal kingdom, especially in vertebrate species. Invertebrate PLB has been restricted to social or object interaction. Here we examined individual PLB in the vinegar flyDrosophila melanogasterby providing voluntary access to a spinning platform – a carousel. We demonstrate that flies exhibit idiosyncratic carousel interactions that qualify as play-like behaviour. While some flies show spontaneous avoidance, others actively seek stimulation, engaging in repeated, prolonged visits to the carousel. We propose that flies voluntarily expose themselves to external forces to intentionally receive exafferent stimulation. Self stimulation provides an efficient way to improve self-perception via internal model training and can shape multisensory integration.One-Sentence SummaryVinegar flies seek passive movement.
Human iPSC-derived neural stem cells display a radial glia-like signaturein vitroand favorable long-term safety in transplanted mice
Authors: Luciani Marco , Garsia Chiara , Beretta Stefano , Petiti Luca , Peano Clelia , Merelli Ivan , Cifola Ingrid , Miccio Annarita , Meneghini Vasco , Gritti Angela 
Published: August 2023

ABSTRACTHuman induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NSCs) are a promising source for cell therapy approaches to treat neurodegenerative and demyelinating disorders. Despite ongoing efforts to characterize hiPSC-derived cellsin vitroandin vivo, we lack comprehensive genome- and transcriptome-wide studies addressing hiPSC-NSC identity and safety, which are critical for establishing accepted criteria for prospective clinical applications.Here, we evaluated the transcriptional and epigenetic signatures of hiPSCs and differentiated hiPSC-NSC progeny, finding that the hiPSC-to-NSC transition results in a complete loss of pluripotency and the acquisition of a radial glia-associated transcriptional signature. Importantly, hiPSC-NSCs share with somatic human fetal NSCs (hfNSCs) the main transcriptional and epigenetic patterns associated with NSC-specific biology.In vivo, long-term observation (up to 10 months) of mice intracerebrally transplanted as neonates with hiPSC-NSCs showed robust engraftment and widespread distribution of human cells in the host brain parenchyma. Engrafted hiPSC-NSCs displayed multilineage potential and preferentially generated glial cells. No hyperproliferation, tumor formation, or expression of pluripotency markers was observed. Finally, we identified a novel role of the Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) in the regulation of astroglial commitment of hiPSC-NSCs.Overall, these comprehensivein vitroandin vivoanalyses provide transcriptional and epigenetic reference datasets to define the maturation stage of NSCs derived from different hiPSC sources, and to clarify the safety profile of hiPSC-NSCs, supporting their continuing development as an alternative to somatic hfNSCs in treating neurodegenerative and demyelinating disorders.
Anti-PD-1-iRGD Peptide Conjugate Boosts Antitumor Efficacy via Engagement Augmentation and Penetration Enhancement of T cells
Authors: Pan Yunfeng , Xue Qi , Yang Yi , Shi Tao , Wang Hanbing , Song Xueru , Yang Xueyi , Liu Baorui , Song Zhentao , Li Jie P. , Wei Jia 
Published: August 2023

AbstractDespite the important breakthroughs of immune-checkpoint inhibitors (ICIs) in recent years, the overall objective response rate (ORR) remains limited in various cancers. Here, we synthesized programmed cell death protein-1 (PD-1) antibody iRGD conjugate (αPD-1-(iRGD)2) through glycoengineering and bio-orthogonal reaction. αPD-1-(iRGD)2exhibited extra iRGD receptor dependent affinity to several cancer cell lines rather than normal cell lines. Via dual targeting, αPD-1-(iRGD)2engageed tumor cells and T cells thus mediating T cell activation and facilitating tumor elimination. Besides, the attachment of iRGD impressively improved the penetrability of both PD-1 antibody and PD-1+T cells. In multiple syngeneic mouse models, αPD-1-(iRGD)2effectively reduced tumor growth with satisfactory biosafety. Moreover, results of flow cytometry and single-cell RNA-seq revealed that αPD-1-(iRGD)2remodeled the tumor microenvironment (TME) and expanded a unique population of “better effector” CD8+tumor infiltrating T cells (TILs) expressing stem and memory associated genes includingTcf7,Il7r,Lef1andBach2. Conclusively, αPD-1-(iRGD)2could be a novel and promising therapeutic approach for cancer immunotherapy.Statement of significanceDesigned against the clinical dilemma of unsatisfied response rate after contemporary cancer immunotherapy, αPD-1-(iRGD)2engages T cells and tumor cells, promotes T cell infiltration and expands a unique population of “better effectors” with enhanced therapeutic potential for the treatment of cancer.
On Casein Kinase-2 (CK2) deregulation in NSCLC: an enzyme subunit-centered approach
Authors: Pérez George V. , Chen Li , Chenyi Deng , Ying Yin , Qiang Zhao , Zhiwei Zhang , Ke Yang , Perea Silvio E. , Perera Yasser 
Published: August 2023

AbstractCK2 is considered a constitutively active protein kinase promoting/supporting several neoplastic properties and inducing a so-called non-oncogene addiction in tumor cells. Compared to the extensive body of pre-clinical research, the translational and clinical information on CK2 is still limited. The holoenzyme, composed by a tetrameric array of two catalytic (CSNK2A1 and/or CSNK2A1) and two regulatory (CSNK2B) subunits, remains to be clinically validated. Herein, we interrogated available cancer multiomics databases to unravel CK2 deregulated expression in NSCLC. We focused our analysis on individual CK2 subunits assuming subunit-specific tumor supportive roles across cancers and particularly, within two major NSCLC subtypes. Moreover, we performed meta-analysis to uncover associations between CK2 expression and patient survival, as well as further correlations analysis with components of the tumor-microenvironment. The genomic and transcriptomic data analysis was complemented by IHC evaluation of CSNK2A1, CSNK2A2 and CSNK2B subunit expression, and CK2 enzymatic activity thereof. Overall, our data suggests that epigenetic, transcriptional and post-transcriptional regulatory mechanisms rather than mutational/gene amplification events may account for differential CK2 subunits expression/activity in NSCLC. Of note, CSNK2A1 and CSNK2B mRNA up-regulation consistently determine a worse patient prognosis in LUAD and correlated with increased infiltration of MDSCs/CAFs. Importantly, we corroborated that CK2 protein subunits levels and enzymatic activity are significantly exacerbated in LUAD and LUSC, but only CSNK2A1 positively correlated with tumor size and disease stage in the analyzed patient cohort, thus supporting our transcriptomic-based correlation analysis. Finally, we concluded that CSNK2A1 alone and/or the homo-tetramer thereof may be more instrumental to support NSCLC than CSNK2A2; thus, tailored drugs against these molecular CK2 entities may achieve better therapeutic windows at least for advanced lung cancer treatment.
The integrity of perineuronal nets in the amygdala as a key factor in the resilience to social isolation stress in old mice
Authors: Hidalgo-Cortés José , Mañas-Ojeda Aroa , Olucha-Bordonau Francisco E. , García-Mompó Clara , Castillo-Gómez Esther 
Published: August 2023

AbstractMajor depression is the most prevalent neuropsychiatric disorder in elderly population, affecting more than 20% individuals over 60 years old, especially women. In this age range, social isolation is a major risk factor for depression. While there is a significant positive association between social isolation and depression in the elderly population, the neurobiological basis of this association is complex and still poorly understood. Evidence from animal models and human studies indicates that neuroplasticity, especially that of limbic brain regions, is impaired in depression but, till date, scarce studies address this question in older population. In this regard, animal models devoid of human cultural connotations represent a crucial tool. In the present study, we investigated the impact of chronic isolation stress (CIS) and a subsequent resocialization period in aged male and female mice (∼ 21 months-old), focusing our attention on affective symptoms and the plasticity of parvalbumin-expressing (PV+) neurons in the lateral/basolateral amygdala (LA/BLA). We found that CIS impaired affective behaviour and LA/BLA plasticity only in females. Specifically, CIS induced depressive-like symptoms and decreased the integrity of perineuronal nets (PNN). Resocialization effectively rescued all these impairments. Old males were not affected by CIS but in social conditions showed higher PNN integrity (less plasticity) than females. All together, our results demonstrate that old females are less resilient to CIS than old males and point to the integrity of PNN in the LA/BLA as a key regulator of depressive-like symptoms induced by social isolation.
Muscle-restricted Nox4 knockout partially corrects muscle contractility following spinal cord injury in mice
Authors: Toro Carlos A. , De Gasperi Rita , Aslan Abdurrahman , Johnson Nicholas , Siddiq Mustafa M. , Chow Christine , Zhao Wei , Harlow Lauren , Graham Zachary , Liu Xin-Hua , Sadoshima Junichi , Iyengar Ravi , Cardozo Christopher P 
Published: August 2023

ABSTRACTSpinal cord injury (SCI) results in severe atrophy of skeletal muscle in paralyzed regions, and a decrease in the force generated by muscle per unit of cross-sectional area. Oxidation of skeletal muscle ryanodine 1 receptors (RyR1) reduces contractile force due to reduced binding of calstabin 1 to RyR1 together with altered gating of RyR1. One cause of RyR1 oxidation is NADPH oxidase 4 (Nox4). We have previously shown that in rats, RyR1 was oxidized and bound less calstabin 1 at 56 days after spinal cord injury (SCI) by transection. Here, we used a conditional knock-out mouse model of Nox4 in muscle to investigate the role of Nox4 in reduced muscle specific force after SCI. Peak twitch force in control mice after SCI was reduced by 42% compared to sham-operated controls but was increased by approximately 43% in SCI Nox4 conditional KO mice compared to SCI controls although it remained less than that for sham-operated controls. Unlike what observed in rats, after SCI the expression of Nox4 was not increased in gastrocnemius muscle and binding of calstabin 1 to RyR1 was not reduced in this muscle. The results suggest a link between Nox4 expression in muscle tissue and reduction in muscle twitch force, however further studies are needed to understand the mechanistic basis for this linkage.
Hospitality SME innovation: responses to multifaceted crises
Authors: Dowell David , Bowen Robert , Morris Wyn 
Published: August 2023

PurposeThis research investigates the multifaceted effects of Covid-19, Brexit and climate change on Small and Medium-sized Enterprises (SMEs) in the hospitality sector. Specifically, the authors evaluate the main opportunities, challenges and implications that hospitality businesses face in times of crises, and innovate as a response.Design/methodology/approachThe research adopts a mixed methods approach firstly analysing quantitative data from the Business Insights and Conditions Survey (BICS). Second, qualitative where data are gathered from interviews with a range of hospitality SMEs. The data are analysed independently and then triangulated to gain a deep understanding of the issues faced by hospitality SMEs and their responses.FindingsThis research contributes to knowledge on the impact of economic challenges on the hospitality sector. This research underlines that hospitality businesses face multiple challenges. The findings show that sector has responded with innovations to meet requirements and regulations, some which were forced upon the industry due to changing regulations and some unforced innovations based on the strategic intentions and entrepreneurialism of the business owners.Originality/valueThe paper embeds the pandemic with Brexit and climate change challenges, identifying two distinct types of innovation as SME responses in the hospitality sector. Survival in the hospitality industry is reliant upon adaptations, some brought about by the pandemic and others by Brexit and climate change.
On the estimation of the angle of attack for vertical axis wind turbines
Authors: Ouchene Samir , Smaili Arezki , Fellouah Hachimi 
Published: August 2023

Purpose
This paper aims to investigate the problem of estimating the angle of attack (AoA) and relative velocity for vertical axis wind turbine (VAWT) blades from computational fluid dynamics data.

Design/methodology/approach
Two methods are implemented as function objects within the OpenFOAM framework for estimating the blade’s AoA and relative velocity. For the numerical analysis of the flow around and through the VAWT, 2 D unsteady Reynolds-averaged Navier–Stokes (URANS) simulations are carried out and validated against experimental data.

Findings
To gain a better understanding of the complex flow features encountered by VAWT blades, the determination of the AoA is crucial. Relying on the geometrically-derived AoA may lead to wrong conclusions about blade aerodynamics.

Practical implications
This study can lead to the development of more robust optimization techniques for enhancing the variable-pitch control mechanism of VAWT blades and improving low-order models based on the blade element momentum theory.

Originality/value
Assessment of the reliability of AoA and relative velocity estimation methods for VAWT’ blades at low-Reynolds numbers using URANS turbulence models in the context of dynamic stall and blade–vortex interactions.