bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data
Authors: Mellor Jonathon , Christie Rachel , Guilder James , Paton Robert S , Elgohari Suzanne , Watson Conall , Deeny Sarah , Ward Thomas 
Published: October 2023

AbstractBackgroundAccurate and representative data is vital for precisely reporting the impact of influenza in healthcare systems. Northern hemisphere winter 2022/23 experienced the most substantial influenza wave since the COVID-19 pandemic began in 2020. Simultaneously, new data streams become available within health services because of the pandemic. Comparing these data, surveillance and administrative, supports the accurate monitoring of population level disease trends.MethodsWe analysed admissions rates per capita from four different collection mechanisms covering National Health Service hospital Trusts in England over the winter 2022/23 wave. We adjust for difference in reporting and extracted key epidemic characteristics including the maximum admission rate, peak timing, cumulative season admissions and growth rates by fitting generalised additive models at national and regional levels.ResultsBy modelling the admission rates per capita across surveillance and administrative data systems we show that different data measuring the epidemic produce different estimates of key quantities. Nationally and in most regions the data correspond well for the maximum admission rate, date of peak and growth rate, however, in subnational analysis discrepancies in estimates arose, particularly for the cumulative admission rate.InterpretationThis research shows that the choice of data used to measure seasonal influenza epidemics can influence analysis substantially at sub-national levels. For the admission rate per capita there is comparability in the sentinel surveillance approach (which has other important functions), rapid situational reports, operational databases and time lagged administrative data giving assurance in their combined value. Utilising multiple sources of data aids understanding of the impact of seasonal influenza epidemics in the population.
Sex-specific effects of birth weight on longitudinal behavioural outcomes in children and adolescents
Authors: Byg Lars Meinertz , Wang Carol , Attia John , Pennell Craig 
Published: October 2023

AbstractIntroductionPrevious cross-sectional studies suggest that birth weight (BW) affects the development of aggression-, social- and attention problems differently in boys and girls. We sought to test if these differences could be confirmed in a longitudinal study.MethodsThe Raine Study provided prospectively collected data on perinatal variables and repeated child behaviour checklist assessments from ages five to seventeen. We used linear mixed effects model to determine crude and adjusted relationships between BW and childhood behaviour at a conservative significance threshold. Sensitivity analyses included an age ten teacher assessment.ResultsData on behaviour, BW and sex, was available in 2269 participants. Male sex was associated with increased aggression problems at lower BW compared to females in the crude model (β: -0.436, 98.3%CI: [-0.844, - 0.0253]), but not the adjusted model (β: -0.310, 98.3%CI: [-0.742, 0.140]). Male sex was associated with increased attention problems at lower BW compared to females in both the crude model (β: -0.334, 98.3%CI: [- 0.530, -0.137]) and the adjusted model (β: -0.274, 98.3%CI: [-0.507, -0.0432]). Male sex was associated with increased social problems at lower BW compared to females in both the crude model (β: -0.164, 98.3%CI: [- 0.283, -0.0441]) and the adjusted model (β: -0.148, 98.3%CI: [-0.285, -0.00734]).ConclusionUsing repeated measures from ages 5-17 we were able to show a crude and adjusted male vulnerability to lower BW in the development of attention problems and social problems. We did not find a BW x sex interaction for the development of aggressive behaviour.
Legal Frameworks Upholding Deceased Individuals’ Rights and Enabling the Use of Cadavers in Anatomy Education and Research: A Systematic Review
Authors: Charmode Sundip H. , Sheikh Nishat , Ravi Satish Kumar , Mehra Simmi 
Published: October 2023

AbstractThe study of human cadavers is essential for teaching, advanced training, and research in medical and anatomical sciences. Medical institutions, around the globe presently face the scarcity of cadaver supply. For the majority of countries, unclaimed bodies are still the primary source of cadavers despite guidelines issued by the International Federation of Associations of Anatomists which discourage the use of unclaimed bodies. This study aims to conduct a review of the existing national and international laws safeguarding the several rights of a deceased person. The study also reviews the existing anatomy acts (and related acts) across various countries that facilitate cadaver supply for anatomy education and research. According to PRISMA guidelines an online search was publications in four medical databases (PubMed, Scopus, Web of Sciences, and Google Scholar) was conducted from 1950 till 2022. A research review protocol was registered in PROSPERO prospectively. Using the Mesh terms like cadaver, anatomy education, dead person and rights, body donation program, unclaimed bodies, and anatomy acts. After the application of the eligibility criteria, 149 publications were shortlisted. After review of all the shortlisted articles, laws, and guidelines, using the data extraction checklist prepared by both authors, five (5) international laws; three (3) supreme court case decisions; two (2) high court case decisions; four (4) Indian penal Code Sections and 22 anatomy acts were selected. The review findings will emphasize the distinctions between India’s anatomy acts and those of other developed nations, thereby broadening our perspective as we propose a model anatomy act for uniform implementation across the country with the goal of streamlining the procurement of cadavers.
Integrin-like adhesin CglD confers traction and stabilizes bacterial focal adhesions involved in myxobacterial gliding motility
Authors: Jolivet Nicolas Y. , Han Endao , Belgrave Akeisha M. , Saïdi Fares , Koushki Newsha , Lemon David J. , Faure Laura M. , Fleuchot Betty , Mahanta Utkarsha , Jiang Heng , Sharma Gaurav , Fiche Jean-Bernard , Bratton Benjamin P. , Diallo Mamoudou , Nan Beiyan , Zusman David R. , Sudre Guillaume , Garza Anthony , Nollmann Marcelo , Ehrlicher Allen J. , Théodoly Olivier , Shaevitz Joshua W. , Mignot Tâm , Islam Salim T. 
Published: October 2023

AbstractIntegrins are crucial for eukaryotic cell attachment and motility within the extracellular matrix (ECM) via focal-adhesion formation, with their evolutionary emergence important for the development of multicellularity. Intriguingly, single gliding cells of the predatory deltaproteobacteriumMyxococcus xanthusform bacterial focal-adhesion (bFA) sites; therein, helically-trafficked motors become immobilized at anchored locations through Glt apparatus association with cell-surface integrin αI-domain-like adhesin CglB. Using traction-force, bead-force, and total internal reflection-fluorescence microscopies combined with biochemical approaches, we herein identify the von Willebrand A domain-containing cell-surface lipoprotein CglD to be a β-integrin-like outer-membrane lipoprotein that functionally associates with and anchors the trans-envelope Glt–CglB gliding apparatus, stabilizing and efficiently anchoring this assembly at bFAs. Calcium dependence governs CglD importance, consistent with its integrated ECM eukaryotic cartilage oligomeric matrix protein domains. CglD thus confers mechanosensory and mechanotransductory capabilities to the gliding apparatus, helping explain bFA-mediated trans-envelope force transduction, from inner-membrane-embedded motors to the cell surface.
Applying the area fraction fractionator (AFF) probe for total volume estimations of somatic, dendritic and axonal domains of the nigrostriatal dopaminergic system in a murine model
Authors: Oñate-Ponce Alejandro , Muñoz Catalina , Catenaccio Alejandra , Court Felipe A. , Henny Pablo 
Published: October 2023

AbstractUsing the nigrostriatal dopaminergic system as a case example, we describe a protocol based on Cavalieri’s principle to estimate the total volume of its somatic, nuclear, dendritic and axonal domains in the adult mouse. This protocol requires serial section analysis, a confocal laser scanning microscope (CLSM), and a stereological software combining the serial section manager (SSM) tool and the area fraction fractionator (AFF) probe. The protocol consists of the following steps: 1) systematic random sampling (SRS) of sites across sections for relevant regions of interest (ROI), which in this study included the substantia nigra pars compacta (SNc) and pars reticulata (SNr), the nigrostriatal tract, and the caudate-putamen complex (CP), 2) high resolution image acquisition of all SRS sites within and across sections, 3) loading of images on the previously defined SRS sites, 4) marking of all cellular structures of interest (cSOI) in the images, including perikarya and cell nuclei, dendrites, axonal segments and varicosities, using Cavalieri’s point-counting grids, and 5) estimation of cSOI total volume using the estimated area of each cSOI in every brain section, and the distance between sections. The added volume for all cSOI comprising the nigrostriatal dopaminergic system, in this murine model is around 0.37 mm3, with approximately 5% corresponding to perikarya and cell nuclei, 10% to neuropil/dendrites in substantia nigra, and 85% to axonal segments and varicosities within the CP. The use of a simple quantitative approach to assess the global state of a system may allow quantification of compartment-specific changes that may accompany neurodegenerative processes.
Trypanosoma brucei gambiensegroup 2 experimentalin vivolife cycle: from procyclic to bloodstream form
Authors: Juban Paola , Bart Jean-Mathieu , Segard Adeline , Jamonneau Vincent , Ravel Sophie 
Published: October 2023

AbstractTrypanosoma brucei gambiense(Tbg) group 2 is a subgroup of trypanosomes able to infect humans in West and Central Africa. Unlike other agents causing sleeping sickness such asTbggroup 1 andTrypanosoma brucei rhodesiense, Tbg2 lacks the typical molecular markers associated with resistance to human serum. Only thirty-six strains ofTbg2 have been documented, and therefore, very limited research has been conducted despite its zoonotic nature. Some of these strains are only available in their procyclic form which hinders human serum resistance assays and mechanistic studies. Furthermore, the understanding ofTbg2’s potential to infect tsetse flies and mammalian hosts is limited. In this study, 165Glossina palpalis gambiensisflies were experimentally infected with procyclicTbg2 parasites. 35 days post-infection, 43 flies out of the 80 still alive flies were foundTbg2PCR-positive in the saliva. These flies were able to infect 3 out of the 4 mice used for blood-feeding. Dissection revealed that only six flies really carried mature infections in their midguts and salivary glands. Importantly, a single fly with a mature infection was sufficient to infect a mammalian host. ThisTbg2transmission success confirms thatTbg2 strains can establish in tsetse flies and infect mammalian hosts. The study describes an effectivein vivoprotocol for transformingTbg2 from procyclic to bloodstream form, reproducing the completeTbg2 cycle fromG. p. gambiensisto mice. These findings provide valuable insights intoTbg2’s host infectivity, and will facilitate further research on mechanisms of human serum resistance.
Single cell profiling of del(5q) MDS unveils its transcriptional landscape and the impact of lenalidomide
Authors: Serrano Guillermo , Berastegui Nerea , Díaz-Mazkiaran Aintzane , García-Olloqui Paula , Huerga-Dominguez Sofia , Alfonso-Pierola Ana , Ainciburu Marina , Vilas-Zornoza Amaia , Martin Patxi San , Aguirre-Ruiz Paula , Ullate-Agote Asier , Ariceta Beñat , Lamo de Espinosa Jose , Acha Pamela , Calvete Oriol , Jimenez Tamara , Molero Antonieta , Montoro Julia , Díez-Campelo Maria , Valcarcel David , Solé Francisco , Ochoa Idoia , Prósper Felipe , Ezponda Teresa , Hernaez Mikel 
Published: October 2023

ABSTRACTWhile del(5q) MDS patients comprise a well-defined hematological subgroup, the molecular basis underlying its origin, and the reason behind the relapse after lenalidomide remains unknown. Using scRNA-seq on CD34+progenitor cells from patients with del(5q) MDS we were able to identify cells harboring the deletion, enabling us to deeply characterize the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. We found, across all patients, an enrichment of del(5q) cells in GMP and megakaryocyte-erythroid progenitors not described to date. Interestingly, both del(5q) and non-del(5q) cells presented similar transcriptional lesions when compared to progenitors from healthy individuals, indicating that all cells, and not only those harboring the deletion, are altered in these patients and may contribute to aberrant hematopoietic differentiation. However, GRN analysis revealed a group of regulons with aberrant activity in del(5q) cells that could be responsible for triggering altered hematopoiesis, pointing to a more prominent role of these cells in the phenotype of these patients. An analysis of del(5q) MDS patients achieving hematological response upon lenalidomide treatment showed that the drug reverted several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remained, which may be responsible for potential future relapses. Moreover, lack of hematological response was associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study provides a deep characterization of del(5q) and non-del(5q) cells at single-cell resolution, revealing previously unknown transcriptional alterations that could contribute to disease pathogenesis, or lack of responsiveness to lenalidomide.KEY POINTS– Del(5q) and non-del(5q) CD34+ cells share similar transcriptional alterations, with del(5q) cells presenting additional lesions.– Hematological response to lenalidomide is associated with the reversal of some transcriptional lesions in del(5q) and non-del(5q) cells
Microtubule inner proteins ofPlasmodiumare essential for transmission of malaria parasites
Authors: Hentzschel Franziska , Binder Annika M. , Dorner Lilian P , Herzel Lea , Nuglish Fenja , Sema Meslo , Aguirre-Botero Manuela C. , Cyrklaff Marek , Funaya Charlotta , Frischknecht Friedrich 
Published: October 2023

AbstractMicrotubule inner proteins, MIPs, are microtubule associated proteins that bind to tubulin from the luminal side. MIPs can be found in axonemes to stabilize flagellar beat or within cytoplasmic microtubules.Plasmodiumspp. are the causative agents of malaria that feature different forms across a complex life cycle with both unique and divergent microtubule-based arrays. Here we investigate the role of four MIPs in a rodent malaria parasite for their role in transmission to and from the mosquito. We show by single and double gene deletions that SPM1 and TrxL1, MIPs associated with the subpellicular microtubules are dispensable for transmission from the vertebrate host to the mosquito and back. In contrast, FAP20 and FAP52, MIPs associated with the axonemes of gametes, are essential for transmission to mosquitoes but only if both genes are deleted. In the absence of both, FAP20 and FAP52 the B-tubule of the axoneme partly detaches from the A-tubule resulting in the deficiency of axonemal beating and hence gamete formation and egress. Our data suggest that a high level of redundancy ensures microtubule stability in the transmissive stages ofPlasmodium, which is important for parasite transmission.
Memory consolidation in honey bees is enhanced by down-regulation ofDown Syndrome Cell Adhesion Moleculeand changes its alternative splicing
Authors: Ustaoglu Pinar , McQuarrie David W. J. , Rochet Anthony , Dix Thomas , Haussmann Irmgard U. , Arnold Roland , Devaud Jean-Marc , Soller Matthias 
Published: October 2023

AbstractDown syndrome cell adhesion molecule (Dscam) gene encodes a cell adhesion molecule required for neuronal wiring. A remarkable feature of invertebrateDscamis massive alternative splicing generating thousands of different isoforms from three variable clusters of alternative exons.Dscamexpression and diversity arising from alternative splicing have been studied during development, but whether they exert functions in differentiated brains has not been determined. Here, using honey bees, we find that Dscam expression is critically linked to memory retention as reducing expression by RNAi enhances memory after reward learning in adult worker bees. Moreover, alternative splicing ofDscamis altered in all three variable clusters after learning. Since identical Dscam isoforms engage in homophilic interactions, these results suggest a mechanism to alter inclusion of variable exons during memory consolidation to modify neuronal connections for memory retention.
Histamine originating from the BNST modulates corticostriatal synaptic transmission during early postnatal development
Authors: Márquez-Gómez Ricardo , Parke Brenna , Cras Yasmin , Gullino Sophie L. , Hashemi Parry , Ellender Tommas 
Published: October 2023

AbstractThe neuromodulator histamine regulates key processes in many regions of both the adult and developing brain including the striatum. However, striatal innervation by histaminergic afferents is very sparse making the physiological sources of histamine controversial. Here potential sources of striatal histamine were investigated during early postnatal development and specifically in the second postnatal week, in acute mouse brain slices. Firstly, a combination of whole-cell patch-clamp recordings and optogenetic stimulation demonstrates that during this period exogenously applied histamine modulates the intrinsic properties of developing D1and D2striatal spiny projection neurons (SPNs) as well as synaptic transmission at afferents coming from the mPFC and visual cortex. Secondly, immunohistochemistry for histamine reveals a brain region proximal and caudal to striatum densely innervated by histaminergic axons and corresponding to the oval nucleus of the bed nucleus of stria terminalis (ovBNST). Thirdly, direct electrical stimulation of the ovBNST leads to significant and detectable levels of histamine in the striatum, as assessed by both fast scan cyclic voltammetry and fluorescent histamine sensors. Lastly, electrical stimulation of the ovBNST nucleus, at frequencies mimicking active histaminergic neurons, can release sufficient levels of histamine to modulate excitatory synaptic transmission from mPFC onto striatal SPNs by acting at histamine H3receptors. Together, these results provide evidence for the existence of the ovBNST as an extrastriatal source of histamine during early brain development and postulates a new view of the modus operandi of histamine in that it can cross anatomical boundaries and act as a paracrine neuromodulator.Significance statementHistamine is synthesized by neurons in the hypothalamic tuberomammillary nucleus (TMN) and released from their axons in many brain regions controlling key physiological processes. When dysregulated this can result in neurological and neurodevelopmental disorders such as Tourette’s syndrome and OCD. To understand the physiological roles for histamine and to facilitate the generation of new therapeutic interventions it is key to define the sources of histamine and its mode of action. Here we provide evidence, using the developing striatum as an exemplar, that sources of histamine can lie beyond anatomical boundaries with histamine acting as a paracrine neuromodulator. This also has potential implications for our mechanistic understanding of deep brain stimulation of the BNST in treating severe Tourette’s syndrome and OCD.
Filamentation and inhibition of prokaryotic CTP synthase
Authors: Guo Chen-Jun , Wang Zi-Xuan , Liu Ji-Long 
Published: October 2023

AbstractCTP synthase (CTPS) plays a pivotal role in the de novo synthesis of CTP, a fundamental building block for RNA and DNA, which is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: ATP, UTP, CTP, and GTP. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by virus or prokaryotic pathogens. Utilizing cryo-electron microscopy, we have determined the structure ofEscherichia coliCTPS (ecCTPS) filament in complex with CTP, NADH, and the covalent inhibitor DON, achieving a resolution of 2.8Å. We construct a phylogenetic tree based on differences in filament-forming interfaces and design a variant to validate our hypothesis, providing an evolutionary perspective on the CTPS filament formation. Our computational analysis reveals a solvent-accessible ammonia tunnel upon DON binding. By comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS, differing from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determine and validate the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.
The heme precursor 5-aminolevulinic acid triggers the shutdown of the HemKR signalling system inLeptospira
Authors: Imelio Juan Andrés , Trajtenberg Felipe , Mondino Sonia , Zarantonelli Leticia , Vitrenko Iakov , Lemée Laure , Cokelaer Thomas , Picardeau Mathieu , Buschiazzo Alejandro 
Published: October 2023

SUMMARYHeme and iron metabolic pathways are highly intertwined, both compounds being essential for key biological processes, yet becoming toxic if overabundant. Their concentrations are exquisitely regulated, including via dedicated two-component systems (TCSs) that sense signals and regulate adaptive responses. HemKR is a TCS involved in the control of heme metabolism inLeptospiraspirochetes. However, the signals and molecular means by which HemKR is switched on/off, are still unknown. Moreover, a comprehensive list of HemKR-regulated genes, potentially overlapped with iron-responsive targets, is also missing. Here we show that 5-aminolevulinic acid (ALA), a committed porphyrin biosynthesis precursor, triggers the shutdown of the HemKR pathway by stimulating the phosphatase activity of HemK towards phosphorylated HemR. HemR dephosphorylation leads to differential expression of multiple genes, including of heme metabolism and transport systems. Furthermore, HemR inactivation brings about an iron-deficit tolerant phenotype, synergistically with iron-responsive signalling systems. Such tolerance could be vital during infection in pathogenicLeptospiraspecies, which comprise a conserved HemKR TCS. In sum, HemKR responds to abundance of porphyrin metabolites by shutting down and controlling heme homeostasis, while also contributing to integrate the regulation of heme and iron metabolism in theL. biflexaspirochete model.