bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the paradigm of anhematophagy in male mosquitoes
Authors: Bozic Jovana , Joseph Renuka E. , Krizek Rachel S. , Holley Amber , Laroche Maureen , Benoit Joshua B. , Rasgon Jason L. 
Published: October 2024

AbstractFemale mosquitoes are reproductively obligate bloodfeeders which feed on vertebrate blood to obtain nutrients required for egg production (driving transmission of vector-borne pathogens in the process), and which rely on plant sugars for their non-reproductive energy requirements. Male mosquitoes, on the other hand, are thought to rely exclusively on plant sugars for their energetic needs; indeed, this dichotomy is one of the central tenets of medical entomology. Here, we show that maleCulex tarsalisandAedes aegyptimosquitoes will readily take blood from a membrane feeder when reared under dehydration conditions with no toxic effects. Mosquitoes with impaired humidity detection do not increase their bloodfeeding rates when dehydrated compared to wild-type controls. While conventionally reared males ignore a human host, dehydrated males are attracted to and attempt to probe, with some success, although they cannot access host capillaries. However, they will take blood from a vertebrate host wound. When fed a blood meal containing West Nile virus, male mosquitoes can become infected with and orally transmit the pathogen at rates and titers equivalent to females. Finally, vertebrate DNA, likely from blood, was detected in wild-caught specimens of maleCulex quinquefasciatusmosquitoes from Texas. These data suggest that under some circumstances male mosquitoes may be able to probe and/or ingest blood and transmit pathogens to vertebrate hosts, and that their role in maintaining pathogen transmission cycles should be re-examined.
Functional Phenotyping of MMV Pandemic Response Box Identifies Stage-specific inhibitors Against Blood stagePlasmodium
Authors: Akhila TP , Darsana KM , Chandramohanadas Rajesh 
Published: October 2024

ABSTRACTWide-spread resistance to clinically used antimalarials necessitates the prioritization of novel scaffolds with alternate mechanisms, as possible partner drugs to artemisinin. We utilized the Pandemic Response Box chemical library of the Medicines for Malaria Venture launched in 2019 to identify inhibitors with stage-specific potency and phenotypic signatures againstP. falciparumtowards exploring the possibility of drug repurposing. From this screening, we initially identified 60 molecules active against both drug sensitive (3D7) and chloroquine resistant (Dd2) strains ofP. falciparum. Further, 28 active compounds active below 3µM were prioritized several of which specifically impaired stage-transitions of ring (MMV001014), trophozoite (MMV1593540 and MMV1634402) and schizonts (MMV1580844, MMV1580496, MMV1580173 and MMV1580483) confirmed through microscopic phenotypes and flow cytometry. The ring stage inhibitor, MMV001014, was irreversible, led to no recrudescence and showed antagonistic effects with artemisinin indicative of overlapping mechanism. Both the trophozoite inhibitors exhibited nanomolar IC50with non-compromised digestive vacuole. MMV1593540 was partially additive with artemisinin while antagonistic with chloroquine. Two among the schizont stage inhibitors (MMV1580844 and MMV1580496) appeared to operate through a mechanism driven by the generation of reactive oxygen species and all of them with molecule-specific effect on infected red blood cell (RBC) membrane integrity confirmed through confocal microscopy. Taken together, these results highlight interesting starting points derived from MMV’s Pandemic Response Box for repurposing to combat Malaria that continues to morbidly affect the developing world.ImportanceMalariacaused by infectious parasites belonging to thePlasmodiumfamily continues to morbidly affect the marginalized populations. The situation is further complicated by lack of mass vaccination, drug resistance, and emergence of new parasitic forms. To alleviate the threat of drug resistance, it is important to identify new drugs acting through mechanisms distinct from the existing ones such as artemisinin. This work describes the screening of a chemical compound library against blood stage development of malaria parasites and prioritization of molecules that can inhibit parasite development in a stage-specific manner. Several of these compounds demonstrate nanomolar potency against sensitive and resistant forms of the parasites acting through distinctive mechanisms. Exploring the modes of action of these molecules will facilitate their optimization and possible clinical applications against the deadly diseases,Malaria.
Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals
Authors: Harris Rebecca M. , Whitfield Troy , Blanton Laura V. , Skaletsky Helen , Blumen Kai , Hyland Phoebe , McDermott Em , Summers Kiana , Hughes Jennifer F. , Jackson Emily , Teglas Petra , Liu Bingrun , Chan Yee-Ming , Page David C. 
Published: October 2024

SummaryThe origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells. Across the autosomes, 8 genes responded with a significant change in expression to testosterone, 34 to estradiol, and 32 to sex chromosome complement with no overlap between the groups. No sex-chromosomal genes responded significantly to testosterone or estradiol, but X-linked genes responded to sex chromosome complement in a remarkably stable manner across cell types. Through leveraging a four-state study design, we successfully separated the independent actions of testosterone, estradiol, and sex chromosome complement on genome-wide gene expression in humans.
Focal Adhesion Kinase (FAK) inhibition induces membrane accumulation of aquaporin2 (AQP2) through endocytosis inhibition and actin depolymerization in renal epithelial cells
Authors: Tchakal-Mesbahi Asma , He Jinzhao , Zhu Shuai , Huang Ming , Fukushima Kazuhiko , Bouley Richard , Brown Dennis , Lu Hua A. J. 
Published: October 2024

AbstractCellular trafficking of the water channel aquaporin 2 (AQP2) is regulated by the actin cytoskeleton in collecting duct principal cells (PC) to maintain proper water balance in animals. Critical actin depolymerization/polymerization events are involved in both constitutive AQP2 recycling, and the pathway stimulated by vasopressin receptor signaling. Focal adhesion kinase (FAK) plays an important role in modulating the actin cytoskeleton through inhibiting small GTPases, and multiple studies have shown the involvement of FAK in insulin and cholesterol trafficking through actin regulation. To understand whether FAK contributes to water reabsorption by the kidney, we performed a series of in vitro experiments to examine the involvement of FAK and its signaling in mediating AQP2 trafficking in cultured renal epithelial cells. Our data showed that FAK inhibition by specific inhibitors caused membrane accumulation of AQP2 in AQP2expressing LLCPK1 cells by immunofluorescence staining. AQP2 membrane accumulation induced by FAK inhibition is associated with significantly reduced endocytosis of AQP2 via the clathrin-mediated endocytosis pathway. Moreover, AQP2 membrane accumulation induced by FAK inhibition also occurred in cells expressing the constitutive dephosphorylation mutant of AQP2, S256A. This was confirmed by immunoblotting using a specific antibody against phospho-serine 256 AQP2, supporting a phosphorylation independent mechanism. Finally, we demonstrated that inhibition of FAK caused reduced RhoA signaling and promoted F-actin depolymerization. In conclusion, our study identifies FAK signaling as a pathway that could provide a novel therapeutical avenue for AQP2 trafficking regulation in water balance disorders.
Unconventional binding of Calmodulin to CHK2 kinase inhibits catalytic activity
Authors: Horne Christopher R. , Wang Tingting , Young Samuel N. , Dite Toby A. , Nyvall Hunter G. , Suresh Sushant , Davies Katherine A. , Mather Lucy J. , Dagley Laura F. , Manning Gerard , Means Anthony R. , Burke John E. , Petersen Janni , Scott John W. , Murphy James M. 
Published: October 2024

ABSTRACTCalmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+sensor. Ca2+binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory pseudosubstrate sequence C-terminal to the kinase domain in members of the Ca2+-CaM dependent protein kinase (CAMK) family, and relieves inhibition to promote catalytic activity. Here, we report an unexpected mechanism by which CaM can bind CHK2 kinase to inhibit its kinase activity. Using biochemical, biophysical, structural mass spectrometry, and cellular approaches, we identify a direct interaction of Ca2+-CaM with the CHK2 kinase domain that suppresses CHK2 catalytic activity in vitro and is crucial for cell proliferation in human cells following DNA damage. Our findings add direct suppression of kinase activity to the repertoire of CaM’s functions, complementing the paradigmatic mechanism of promoting kinase activity through autoinhibitory domain sequestration.
Computational neurodevelopment: infant decision-making in changing environments
Authors: Adams Rick A. , Billing Addison , Baljer Levente , Smith Eleanor , Cooper Rob J. , Lawson Rebecca P. 
Published: October 2024

AbstractIn recognition of the fact that most psychiatric conditions have neurodevelopmental origins, there is an increasing interest in applying the methodological and conceptual approaches from computational psychiatry to developmental cohorts. However, the challenge of acquiring and modelling behavioural responses in very young infants has thus far proven difficult to overcome. To address this we developed a novel gaze-contingent, cued-reversal paradigm that allowed 6-10 month old infants to make overt behavioural responses to assess learning of expectations and updating of behaviour in response to change. We then fit computational models to infant behaviour and, for the first time, were able to validate the winning model to the same standards as would be expected of adults (e.g. good parameter recoverability, model identifiability and simulated behavioural responses). Similar to prior findings in adults, model-based prediction error measures correlated with post-switch increases in pupil size; consistent with noradrenaline’s hypothesised role in learning about change. Data-driven clustering based on model parameters revealed two infant behavioural subtypes hidden within the data; one with a perseverating profile and the other with a more exploratory decision-making pattern. This approach sheds new light on the ‘classic’ finding that all infants under 12 months tend to perseverate. Crucially, there were no significant differences in age between the clusters, but differences in terms of adaptive skills and temperament measured via gold-standard developmental assessments. These results prime the field for infant computational psychiatry, demonstrating that we can reliably fit models to infant data and that the parameters from such models can identify subgroups with distinct cognitive profiles that are superior to those derived from the behavioural data alone.
Structural characterization of pyruvic oxime dioxygenase, a key enzyme of heterotrophic nitrification
Authors: Tsujino Shuhei , Yamada Yusuke , Senda Miki , Nakamura Akihiko , Senda Toshiya , Fujiwara Taketomo 
Published: October 2024

ABSTRACTNitrification by heterotrophic microorganisms is an important part of the nitrogen cycle in the environment. The enzyme responsible for the core function of heterotrophic nitrification is pyruvic oxime dioxygenase (POD). POD is a non-heme Fe(II)-dependent enzyme that catalyzes the dioxygenation of pyruvic oxime to produce pyruvate and nitrite. To analyze the catalytic mechanism of POD, the crystal structure of POD fromAlcaligenes faecalis(AfPOD) was determined at 1.76 Å resolution. The enzyme is a homo-tetramer and the subunit structure is homologous to those of class II aldolases, in particular a zinc-dependent L-fuculose-1-phosphate aldolase. The active site of the subunit is located at the bottom of a cleft formed with an adjacent subunit. The iron ion at the active site is coordinated by three histidines and three water molecules in an octahedral geometry. The putative oxygen tunnel was connected between the active site and the central cavity of the tetramer. The N-terminal region of AfPOD, which is essential for catalytic activity, is disordered in the crystal. Structure prediction with AlphaFold2 combined with mutational experiments suggested that the disordered N-terminal region adopts an α-helix conformation and participates in the formation of the active site. The catalytic mechanism of the dioxygenase reaction by POD is discussed on the basis of the molecular docking model.IMPORTANCEOur knowledge of nitrification has increased considerably in recent decades with the discovery of new nitrifying microorganisms and the characterization of their biochemical processes. Some heterotrophic bacteria and fungi are known to show nitrification activities, but the molecular mechanisms had been poorly understood. Here, we performed a structural characterization of POD, a key enzyme in heterotrophic nitrification that produces nitrite from ammonia using pyruvic oxime as an intermediate. Structural and enzymatic analyses revealed that POD is a unique dioxygenase with features such as an aldolase backbone, an N-terminal α-helix, and an oxygen tunnel. Our results provide insights not only into the molecular mechanisms but also into the design of specific inhibitors of heterotrophic nitrification.
Mid1deletion leads to cognitive dysfunction in Opitz syndrome by regulates neural rhythms through the inhibition of p-Creb by PP2Ac
Authors: Yang Ziye , Li Pengxiang , Chen Yue , Guo Xiaoyu , Liu Ping , Ni Guangjian , Liu Shuang , Chen Liqun , Ming Dong 
Published: October 2024

AbstractMID1 is an E3 ubiquitin ligase of the tripartite motif (TRIM) subfamily of RING-containing protein1. MID1 is involved in many basic biological processes, especially during embryonic development. Mutation, truncation or complete deletion ofMID1gene is the cause of Opitz G/BBB syndrome (OS). OS is a rare genetic disease of nervous system, which is characterized by midline structural development defects during embryogenesis, including structural brain abnormalities, developmental retardation and mental retardation2. Although the function ofMID1has been studied for many years, the effect and mechanism of complete deletion ofMID1gene on OS nervous system still need to be further explored. Here we find thatMid1gene is necessary for the normal development of hippocampus (HPC), andMid1gene knockout (Mid1-/y) mice showed a significant decrease in α rhythm in HPC and abnormal synchronization of γ rhythm in prefrontal cortex and hippocampus (PFC-HPC), showing decreased synaptic plasticity and learning and memory dysfunction.
Global fit to
b→cτν
anomalies as of Spring 2024
Authors: Iguro Syuhei , Kitahara Teppei , Watanabe Ryoutaro 
Published: October 2024

Recently, several new experimental results of the test of lepton flavor universality (LFU) in B→D(*) semileptonic decays were announced: the first result of RD from the LHCb run 1 data, the first results of RD and RD* from the LHCb run 2 data, and the first result of RD* from the Belle II collaboration. Including these new data, a global analysis still prefers the violation of the LFU between the tau and light leptons. A new world average of the data from the , LHCb, Belle, and Belle II collaborations is RD=0.342±0.026 and RD*=0.287±0.012. Including this new data, we update a circumstance of the b→cτν¯ measurements and their implications for new physics (NP). Incorporating recent developments for the B→D(*) form factors in the Standard Model, we observe a 4.4σ deviation from the Standard Model prediction. Our updates also include model-independent NP formulas for the related observables and the global fittings of parameters for leptoquark scenarios as well as single NP operator scenarios. Furthermore, we show future potential to indirectly distinguish different NP scenarios with the use of the precise measurements of the polarization observables in B→D(*)τν¯ at the Belle II and the high-pT flavored-tail searches at the LHC. We also discuss an impact on the LFU violation in ϒ→l+l−.

Published by the American Physical Society
2024
Influence of temperature on the cathodic polarization behavior and calcareous deposit properties of X65 steel in sea water
Authors: Zhu Zhenhong , Liang Yi , Li Dapeng , Li Huixin , Du Yanxia 
Published: October 2024

Purpose
This paper aims to investigate how cathodic polarization behavior significantly affects the selection of cathodic protection parameters and the effectiveness of protecting underwater metal structures. Factors such as water depth and operating conditions impact seawater temperature, making it crucial to understand the effects of temperature on cathodic protection parameters for underwater pipelines.

Design/methodology/approach
In this paper, potentiostatic polarization was carried out by three-electrode method, and morphology, X-ray diffraction and electrochemical analysis.

Findings
It was determined that the stable current densities at the minimum negative potential (−0.8 VSSC) for pipeline steel varied at different temperatures: 7°C, room temperature and 60°C. The cathodic protection potential corresponding to the lowest stable current density was observed to be −1.0 VSSC at 7°C and −0.95 VSSC at room temperature and 60°C.

Originality/value
This study elucidates the mechanisms by which different temperatures affect the protective performance of calcareous deposits and current densities.
Factors influencing young adults’ organic food purchase intention on fresh food e-commerce platforms
Authors: Qi Xin , Lv Xinlei , Li Zhigang , Yang Chunbaixue , Li Haoran , Ploeger Angelika 
Published: October 2024

PurposeUnderstanding young adults’ organic food purchasing behavior in the fresh food e-commerce platforms (FFEP) is crucial for expanding the global environmental product market. The study aims to investigate how specific characteristics of platforms and organic food information impact young adults’ perceived value, leading to their subsequent purchase intention.Design/methodology/approachAround 535 valid responses were collected through an online survey and then analyzed applying a two-stage structural equation model (SEM) and artificial neural network (ANN) approach.FindingsResults of this research show that platform characteristics (including system quality and evaluation system) and product information characteristics (including organic label, ingredient information and traceability information) significantly affect young adults’ perceived utilitarian and hedonic value. The platform’s service quality has a strong effect on their perceptions of hedonic value, while the delivery system strongly influences their utilitarian value. Moreover, the perceived value, as a crucial mediator, plays a significant role in moderating the influence of platform and product information characteristics on the purchase intentions of young consumers regarding organic food.Originality/valuePrevious research has overlooked the credence attributes of organic food and particularities of online purchasing, focusing instead on general platform and product characteristics. This study addresses this gap by proposing a more appropriate model that integrates the characteristics of both the platform and product information. This offers theoretical and managerial implications for effectively stimulating organic food consumption among young adults in online environments.
Do all complain the same? Examining the role of luxury hotels reviewer attributes using text mining
Authors: Ali Aafreen , Chittiprolu Vinay , Rongala Sourya , Bellamkonda Raja Shekhar 
Published: October 2024

Purpose
Although extant studies found the determinants of customer complaints in luxury hotels, comparison of complaint severity using reviewer characteristics (nationality, reviewer type and expertise) is limited. This study aims to identify the variation in customers’ complaint attributes among different customer categories.

Design/methodology/approach
This study tried to address this gap by using structural topic modelling and text mining techniques to find the sentiment score, word count, complaints attributes and severity score. The research sample covers luxury hotels in India, and online review text and their associated data has been collected and analysed.

Findings
The authors found that leisure customers wrote lengthier reviews and complained about the facility-related aspects (valet parking, entertainment and amenities) and food-related aspects (food variety, service and menu) while the business customers’ complaint severity score is more on salient aspects (room size, bathroom and staff related services). The international customers wrote lengthier reviews and complained more about the facility-related aspects (amenities, pick-up and entertainment) and core service offerings (stay experience, bathroom, dirtiness and complaint resolution). Whereas domestic customers complained more about stay-related aspects (food variety, quality, services, staff behaviour and stay experience). Also, this study used correlation analysis to find the dependencies between topics and uncovered underlying patterns, trends and associations, aiding in a deeper understanding and interpretation of the complaints. This study can help service providers tailor their services based on customer attributes to ensure maximum customer satisfaction.

Originality/value
The findings of this study can enable hotel service providers to customise their services based on customer attributes to reduce dissatisfaction among customers and promote customer loyalty. The findings of this study can also be used to devise differential promotional strategies for different types of customers.