bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socio-demographic determinants of monkeypox virus preventive behavior: a cross-sectional study in Pakistan
Authors: Jamil Hashaam , Idrees Muhammad , Idrees Kashmala , Tariq Waleed , Sayyeda Qudsia , Asghar Muhammad Sohaib , Tahir Muhammad Junaid , Akram Samra , Ullah Kaleem , Ahmed Ali , Mohanty Aroop , Padhi Bijaya Kumar , Sah Ranjit 
Published: December 2022

AbstractBackgroundMonkeypox, a re-emerging zoonotic infectious disease, is striking the world with serious public health concerns, especially in non-endemic countries. The public’s knowledge and attitude toward the monkeypox virus (MPXV) influence their adherence to preventive strategies. Therefore, we aimed to assess the general public’s knowledge, attitudes, and perceptions (KAP) of MPXV in Pakistan.MethodsWe collected data for this cross-sectional study from 1040 participants via an online self-reported questionnaire from 5thJuly 2022 to 1stAugust 2022. The questionnaire consisted of a total of 29 items in four sections, assessing socio-demographics, knowledge, attitudes, and practices regarding MPXV. The data was analyzed using IBM SPSS V.25, and factors associated with MPXV knowledge, attitude, and practices were identified by using logistic regression analysesResultsA total of1040participants were included. 61.4% were male and 57.2% had graduation level education. Only 34.4% had good knowledge about MPXV and 30% were aware of effectiveness of smallpox vaccine against MPXV. 41.7% had positive attitude with 48.6% agreed that it is a fatal disease and 44.6% were in favor of banning travelling from endemic to non-endemic regions.57.7% had good practices and 69.9% would use protective measures if MPXV become an epidemic. Binary logistic regression analysis revealed that gender and education significantly impacted knowledge (p<0.05). While monthly income status had a significant impact on attitudes (p<0.05). The practices were correlated positively with gender and education (p<0.05).ConclusionThe majority of study participants had inadequate levels of knowledge, and attitudes regarding MPXV. To prevent the emergence and spread of MPXV in Pakistan, a comprehensive strategic framework for public health education must be established and implemented.
Inhibition of the DENV2 and ZIKV RNA polymerases by Galidesivir triphosphate measured using a continuous fluorescence assay
Authors: Deshpande Sandesh , Huo Wenjuan , Shrestha Rinu , Sparrow Kevin , Evans Gary B. , Harris Lawrence D. , Kingston Richard L. , Bulloch Esther M. M. 
Published: December 2022

AbstractMillions of people are infected by the Dengue and Zika viruses each year, which can result in serious illness, permanent disability or death. There are currently no FDA-approved antivirals for treating infection by these viruses. Galidesivir is an adenosine nucleoside analog which can attenuate flavivirus replication in cell-based and animal models of infection. Galidesivir is converted to the triphosphorylated form by host kinases, and subsequently incorporated into viral RNA by viral RNA-dependent RNA polymerases, leading to the termination of RNA synthesis via an unknown mechanism. Here we report the directin vitrotesting of the effects of Galidesivir triphosphate on RNA synthesis by the polymerases of Dengue-2 and Zika virus. Galidesivir triphosphate was chemically synthesized and inhibition of RNA synthesis followed using a continuous fluorescence-based assay. Galidesivir triphosphate was equipotent against the polymerase activity of Dengue-2 and Zika, with IC50values of 42 ± 12 μM and 47 ± 5 μM, respectively. This modest potencyin vitrois consistent with results previously obtained in cell-based antiviral assays and suggests that the binding affinity for Galidesivir triphosphate is similar to the natural ATP substrate that it closely mimics. The inhibition assay we have developed will allow the rapid screening of Galidesivir and related compounds against other flavivirus polymerases, and the availability of Galidesivir triphosphate will allow detailed analysis of its mechanism of action.HighlightsGalidesivir triphosphate was chemically synthesized.A continuous assay detecting double-stranded RNA formation was optimized for polymerase inhibition studies.Galidesivir triphosphate has moderate potency against DENV2 and ZIKA polymerase activity.The availability of Galidesivir triphosphate will facilitate study of its mechanism of action.
Wastewater monitoring of SARS-CoV-2 RNA at K-12 schools: Comparison to pooled clinical testing data
Authors: Kim Sooyeol , Boehm Alexandria B. 
Published: December 2022

AbstractBackgroundWastewater measurements of SARS-CoV-2 RNA have been extensively used to supplement clinical data on COVID-19. Most examples in the literature that describe wastewater monitoring for SARS-CoV-2 RNA use samples from wastewater treatment plants and individual buildings that serve as the primary residence of community members. However, wastewater surveillance can be an attractive supplement to clinical testing in K-12 schools where individuals only spend a portion of their time but interact with others in close proximity, increasing risk of potential transmission of disease.MethodsWastewater samples were collected from two K-12 schools in California and divided into solid and liquid fractions to be processed for detection of SARS-CoV-2. The resulting detection rate in each wastewater fraction was compared to each other and the detection rate in pooled clinical specimens.ResultsMost wastewater samples were positive for SARS-CoV-2 RNA when clinical testing was positive (75% for solid samples and 100% for liquid samples). Wastewater samples continued to test positive for SARS-CoV-2 RNA when clinical testing was negative or in absence of clinical testing (83% for both solid and liquid samples), indicating presence of infected individuals in the schools. Wastewater solids had a higher concentration of SARS-CoV-2 than wastewater liquids on an equivalent mass basis by three orders of magnitude.
Mitochondrial phosphagen kinases support the volatile power demands of motor nerve terminals
Authors: Justs Karlis A. , Sempertegui Sergio , Riboul Danielle V. , Oliva Carlos D. , Durbin Ryan J. , Crill Sarah , Su Chenchen , Renden Robert B. , Fily Yaouen , Macleod Gregory T. 
Published: December 2022

ABSTRACTNeural function relies on cellular energy supplies meeting the episodic demands of synaptic activity, but little is known about the extent to which power demands (energy demands per unit time) fluctuate, or the mechanisms that match supply with demand. Here, in individually-identified glutamatergic motor neuron terminals ofDrosophilalarvae, we leveraged prior macroscopic estimates of energy demand to generate profiles of power demand from one action potential to the next. These profiles show that signaling demands can exceed non-signaling demands 10-fold within milliseconds, and terminals with the greatest fluctuation (volatility) in power demand have the greatest mitochondrial volume and packing density. We elaborated on this quantitative approach to simulate adenosine triphosphate (ATP) levels during activity and drove ATP production as a function of the reciprocal of the energy state, but this canonical feedback mechanism appeared to be unable to prevent ATP depletion during locomotion. Muscle cells possess a phosphagen system to buffer ATP levels but phosphagen systems have not been described for motor nerve terminals. We examined these terminals for evidence of a phosphagen system and found the mitochondria to be heavily decorated with an arginine kinase, the key element of invertebrate phosphagen systems. Similarly, an examination of mouse cholinergic motor nerve terminals found mitochondrial creatine kinases, the vertebrate analogues of arginine kinases. Knock down of arginine kinase inDrosophilaresulted in rapid depletion of presynaptic ATP during activity, indicating that, in motor nerve terminals, as in muscle, phosphagen systems play a critical role in matching power supply with demand.SIGNIFICANCEFailure of metabolic processes to supply neurons with energy at an adequate rate can lead to synaptic dysfunction and cell death under pathological conditions. Using a quantitative approach at fruit fly motor nerve terminals we generated the first temporal profiles of presynaptic power demand during locomotor activity. This approach revealed challenges for the known mechanisms that match cellular power supply to demand. However, we discovered that motor nerve terminals in fruit flies and mice alike are supported by phosphagen systems, more commonly seen in muscles where they store energy and buffer mismatch between power supply and demand. This study highlights an understudied aspect of neuronal bioenergetics which may represent a bulwark against the progression of some neuropathologies.
Reactivation of early-life stress-sensitive neuronal ensembles contributes to lifelong stress hypersensitivity
Authors: Balouek Julie-Anne , Mclain Christabel , Minerva Adelaide R. , Rashford Rebekah L. , Bennett Shannon N. , Peña Catherine Jensen 
Published: December 2022

ABSTRACTEarly-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human and animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, the neurobiological basis of such stress sensitization remains largely unexplored. We hypothesized that ELS-induced stress sensitization would be detectable at the level of neuronal ensembles, such that cells activated by ELS would be more reactive to adult stress. To test this, we leveraged transgenic mice to genetically tag, track, and manipulate experience-activated neurons. We found that in both male and female mice, ELS-activated neurons within the nucleus accumbens (NAc), and to a lesser-extent the medial prefrontal cortex, were preferentially reactivated by adult stress. To test whether reactivation of ELS-activated ensembles in the NAc contributes to stress hypersensitivity, we expressed hM4Dis receptor in control or ELS-activated neurons of pups and chemogenetically inhibited their activity during experience of adult stress. Inhibition of ELS-activated NAc neurons, but not control-tagged neurons, ameliorated social avoidance behavior following chronic social defeat stress in males. These data provide evidence that ELS-induced stress hypersensitivity is encoded at the level of corticolimbic neuronal ensembles.
Tobacco smoke exposure results in recruitment of inflammatory airspace monocytes and accelerated growth ofMycobacterium tuberculosis
Authors: Corleis Bjӧrn , Tzouanas Constantine N. , Wadsworth Marc H , Cho Josalyn L , Linder Alice H , Schiff Abigail E , Dickey Amy K , Medoff Benjamin D , Shalek Alex K. , Kwon Douglas S 
Published: December 2022

AbstractTobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive toMycobacterium tuberculosis(Mtb) growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current- and never-smokers by performing single-cell RNA-sequencing (scRNA-seq), flow cytometry, and functional assays. We observed enrichment of immature inflammatory monocytes in the lungs of smokers compared to non-smokers. These monocytes exhibited phenotypes consistent with recent recruitment from blood, ongoing differentiation, increased activation, and states similar to those with chronic obstructive pulmonary disease (COPD). Using integrative scRNA-seq and flow cytometry, we identify CD93 as a marker for a subset of these newly recruited smoking-associated lung monocytes and further provide evidence that recruitment of monocytes into the lung is mediated by CCL11 binding to CCR2. We also show that these cells exhibit elevated inflammatory responses upon exposure toMtband accelerated intracellular growth ofMtbcompared to mature macrophages. This elevatedMtbgrowth could be inhibited with an anti-inflammatory small molecule, providing a direct connection between smoking-induced pro-inflammatory states and permissiveness toMtbgrowth. Our findings suggest a model in which smoking leads to recruitment of immature inflammatory monocytes from the periphery to the lung via CCL11-CCR2 interactions, which results in the accumulation of theseMtbpermissive cells in the airway. This work defines how smoking may lead to increased susceptibility toMtband identifies novel host-directed therapies to reduce the burden of TB among those who smoke.One Sentence SummaryInflammatory monocytes are recruited to the airways of smokers where they may contribute to more rapid growth ofMycobacterium tuberculosisin the lungs.
Connectome-based predictive modeling shows sex differences in brain-based predictors of memory performance
Authors: Ju Suyeon , Horien Corey , Shen Xilin , Abuwarda Hamid , Trainer Anne , Constable R Todd , Fredericks Carolyn A. 
Published: December 2022

AbstractAlzheimer’s disease (AD) takes a more aggressive course in women than men, with higher prevalence and faster progression. Amnestic AD specifically targets the default mode network (DMN), which subserves short-term memory; past research shows relative hyperconnectivity in the posterior DMN in aging women. Higher reliance on this network during memory tasks may contribute to women’s elevated AD risk. Here, we applied connectome-based predictive modeling (CPM), a robust linear machine-learning approach, to the Lifespan Human Connectome Project-Aging (HCP-A) dataset (n=579). We sought to characterize sex-based predictors of memory performance in aging, with particular attention to the DMN. Models were evaluated using cross-validation both across the whole group and for each sex separately. Whole-group models predicted short-term memory performance with accuracies ranging from ρ=0.21-0.45. The best-performing models were derived from an associative memory task-based scan. Sex-specific models revealed significant differences in connectome-based predictors for men and women. DMN activity contributed more to predicted memory scores in women, while within- and between-visual network activity contributed more to predicted memory scores in men. While men showed more segregation of visual networks, women showed more segregation of the DMN. We demonstrate that women and men recruit different circuitry when performing memory tasks, with women relying more on intra-DMN activity and men relying more on visual circuitry. These findings are consistent with the hypothesis that women draw more heavily upon the DMN for recollective memory, potentially contributing to women’s elevated risk of AD.
Intraspecific chemodiversity provides plant individual- and neighbourhood-mediated associational resistance towards aphids
Authors: Ziaja Dominik , Müller Caroline 
Published: December 2022

AbstractSome plant species express an extraordinarily high intraspecific diversity in phytochemicals (= chemodiversity). As discussed for biodiversity, higher chemodiversity may provide better protection against environmental stress, including herbivory. However, little is known about whether the resistance of a plant individual towards herbivores is mostly governed by its own chemodiversity or by associational resistance provided by conspecific neighbours.To investigate the role of chemodiversity in plant-aphid interactions, we used the AsteraceaeTanacetum vulgare, whose individuals differ pronouncedly in the composition of leaf terpenoids, forming distinct chemotypes. Plants were set-up in a field consisting of 60 plots, each containing five individuals of either the same or different chemotypes. Presence of winged aphids, indicating aphid attraction, and abundance of winged and unwinged aphids, indicating fitness, were scored weekly on each plant, focusing on three commonly occurring aphid species specialised onT. vulgare. During the peak abundance of aphids, leaf samples were taken from all plants for re-analyses of the terpenoid composition and quantification of terpenoid chemodiversity, calculated on an individual plant (Shannon index, Hsind) and plot level (Hsplot).Aphid attraction was neither influenced by chemotype nor plot-type. The real-time odour environment may be very complex in this setting, impeding clear preferences. In contrast, the abundance was affected by both chemotype and plot-type. On average, moreUroleucon tanacetiaphids were found on plants of two of the chemotypes growing in homogenous compared to heterogenous plots, supporting the associational resistance hypothesis. ForMacrosiphoniella tanacetariathe probability of presence on a plant differed between plot-types on one chemotype. Terpenoid chemodiversity expressed as a gradient revealed negative Hsploteffects onU. tanaceti, but a positive correlation of Hsindwith the abundance ofM. tanacetaria. Aphids ofM. fuscoviridewere not affected by any level of chemodiversity.Synthesis. This study shows that not only the chemotype and chemodiversity of individual plants but also that of conspecific neighbours influence plant-herbivore interactions. These effects are highly specific with regard to the plant chemotype, the aphid species as well as its morphs (winged vs. unwinged). Furthermore, our results highlight the importance of analysing chemodiversity at different levels.
Cell surface composition and ionic strength mediate fast sedimentation in the cyanobacteriumSynechococcus elongatusPCC 7942
Authors: Zedler Julie A. Z. , Michel Marlene , Pohnert Georg , Russo David A. 
Published: December 2022

AbstractCyanobacteria are photosynthetic prokaryotes of high ecological and biotechnological relevance that have been cultivated in laboratories around the world for more than 70 years. Prolonged laboratory culturing has led to multiple microevolutionary events and the appearance of a large number of “domesticated” substrains among model cyanobacteria. Despite its widespread occurrence, strain domestication is still largely ignored. In this work we describeSynechococcus elongatusPCC 7942–KU, a novel domesticated substrain of the model cyanobacteriumSynechococcus elongatusPCC 7942, which presents a fast-sedimenting phenotype. Under higher ionic strengths the sedimentation rate increases leading to complete sedimentation in just 12 h. Through whole genome sequencing and gene deletion, we demonstrate that the Group 3 alternative sigma factor F (SigF) plays a key role in cell sedimentation. In addition, sedimentation analysis of an unpiliated mutant and differences in surface hydrophobicity suggest that mutations in SigF lead to significant changes of cell surface structures and, consequentially, to the appearance of a fast-sedimenting phenotype. This work sheds light on the determinants of the planktonic to benthic transitions and provides genetic targets to generate fast-sedimenting strains that could unlock cost-effective cyanobacterial harvesting at scale.
GelMap: Intrinsic calibration and deformation mapping for expansion microscopy
Authors: Damstra Hugo G.J. , Passmore Josiah B. , Serweta Albert K. , Koutlas Ioannis , Burute Mithila , Meye Frank J. , Akhmanova Anna , Kapitein Lukas C. 
Published: December 2022

ABSTRACTExpansion microscopy (ExM) is a powerful technique to overcome the diffraction limit of light microscopy by physically expanding biological specimen in three dimensions. Nonetheless, using ExM for quantitative or diagnostic applications requires robust quality control methods to precisely determine expansion factors and to map deformations due to anisotropic expansion. Here we present GelMap, a flexible workflow to introduce a fluorescent grid into pre-expanded hydrogels that scales with expansion and reports deformations. We demonstrate that GelMap can be used to precisely determine the local expansion factor and to correct for deformations without the use of cellular reference structures or pre-expansion ground truth images. Moreover, we show that GelMap aids sample navigation for correlative uses of expansion microscopy. Finally, we show that GelMap is compatible with expansion of tissue and can be readily implemented as a quality control step into existing ExM workflows.
NEK7 activates the NLRP1 Inflammasome
Authors: Muela-Zarzuela Inés , Gallardo-Orihuela Andrea , Pino-Ángeles Almudena , Suarez-Rivero Juan Miguel , Boy-Ruiz Daniel , de Gregorio-Procopio Marta , Oroz Javier , Mbalaviele Gabriel , Cordero Mario D. 
Published: December 2022

AbstractInflammasomes including those assembled by NLRP1 and NLRP3 regulate the innate immune system by inducing interleukin (IL)-1β and IL-18 maturation. Inflammasomes are functionally regulated by post-translational modifications such as phosphorylation. The current paradigm posits that NEK7 is the essential and seletive activator of NLRP3; whether this kinase interacts with NLRP3 structurally-related member, NLRP1, has never been explored. Here, we find that NEK7 binds to NLRP1 and promotes its activation independently of NLRP3. IL-1β maturation induced by NLRP1 or NLRP3 inflammasome activators, but not those of the NLRC4 or AIM2 inflammasome is impared in Nek7 deficient cells. This discovery expands the spectrum of NEK7 actions in the regulation of inflammasome pathways.
Laminar Neural Dynamics of Auditory Evoked Responses: Computational Modeling of Local Field Potentials in Auditory Cortex of Non-Human Primates
Authors: Chien Vincent S.C. , Wang Peng , Maess Burkhard , Fishman Yonatan , Knösche Thomas R. 
Published: December 2022

AbstractEvoked neural responses to sensory stimuli have been extensively investigated in humans and animal models both to enhance our understanding of brain function and to aid in clinical diagnosis of neurological and neuropsychiatric conditions. Recording and imaging techniques such as electroencephalography (EEG), magnetoencephalography (MEG), local field potentials (LFPs), and calcium imaging provide complementary information about different aspects of brain activity at different spatial and temporal scales. Modeling and simulations provide a way to integrate these different types of information to clarify underlying neural mechanisms.In this study, we aimed to shed light on the neural dynamics underlying auditory evoked responses by fitting a rate-based model to LFPs recorded via multi-contact electrodes which simultaneously sampled neural activity across cortical laminae. Recordings included neural population responses to best-frequency (BF) and non-BF tones at four representative sites in primary auditory cortex (A1) of awake monkeys. The model considered major neural populations of excitatory, parvalbumin-expressing (PV), and somatostatin-expressing (SOM) neurons across layers 2/3, 4, and 5/6. Unknown parameters, including the connection strength between the populations, were fitted to the data. Our results revealed similar population dynamics, fitted model parameters, predicted equivalent current dipoles (ECD), tuning curves, and lateral inhibition profiles across recording sites and animals, in spite of quite different extracellular current distributions. We found that PV firing rates were higher in BF than in non-BF responses, mainly due to different strengths of tonotopic thalamic input, whereas SOM firing rates were higher in non-BF than in BF responses due to lateral inhibition.In conclusion, we demonstrate the feasibility of the model-fitting approach in identifying the contributions of cell-type specific population activity to stimulus-evoked LFPs across cortical laminae, providing a foundation for further investigations into the dynamics of neural circuits underlying cortical sensory processing.