bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain Morphometry and Chronic Inflammation in Bangladeshi Children Growing up in Extreme Poverty
Authors: Turesky Ted K. , Pirazzoli Laura , Shama Talat , Kakon Shahria Hafiz , Haque Rashidul , Islam Nazrul , Someshwar Amala , Gagoski Borjan , Petri William A. , Nelson Charles A. , Gaab Nadine 
Published: December 2021

ABSTRACTOver three hundred million children live in environments of extreme poverty, and the biological and psychosocial hazards endemic to these environments often expose these children to infection, disease, and inflammatory responses. Chronic inflammation in early childhood has been associated with diminished cognitive outcomes, and despite this established relationship, the mechanisms explaining how inflammation affects brain development are not well known. Importantly, the prevalence of chronic inflammation in areas of extreme poverty raises the possibility that it may serve as a mechanism explaining the known relationship between low socioeconomic status (SES) and altered brain development. To examine these potential pathways, seventy-nine children growing up in an extremely poor, urban area of Bangladesh underwent MRI scanning at six years of age. Structural brain images were submitted to Mindboggle software, a Docker-compliant and high-reproducibility tool for regional estimations of volume, surface area, cortical thickness, sulcal depth, and mean curvature. C-reactive protein was assayed at eight time points between infancy and five years of age and the frequency with which children had elevated concentrations of inflammatory marker represented the measure of chronic inflammation. Childhood SES was measured with maternal education and income-to-needs (i.e., monthly household income divided by the number of household members). Chronic inflammation predicted volume in bilateral basal ganglia structures and mediated the link between maternal education and bilateral putamen volumes. These findings suggest that chronic inflammation is associated with brain morphometry in the basal ganglia, predominantly the putamen, and further offers inflammation as a potential mechanism linking SES to brain development.
Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
Authors: Takeda Tomoki , Yamano Shotaro , Goto Yuko , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Daghlian George , Hong Young Kwon , Yoshimatsu Yasuhiro , Hirashima Masanori , Kobashi Yoichiro , Okamoto Kenzo , Kishimoto Takumi , Umeda Yumi 
Published: December 2021

AbstractBackgroundIn Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose-response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace.MethodsMale and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3 CWAAP-A for 6 hours/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 hour, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 hours/day for 2 days.ResultsCWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3 and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3 CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3 was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages.ConclusionsPulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3 CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.
Structural development of amyloid precursors in insulin B chain and the inhibition effect by fibrinogen
Authors: Yamamoto Naoki , Inoue Rintaro , Makino Yoshiteru , Shibayama Naoya , Naito Akira , Sugiyama Masaaki , Chatani Eri 
Published: December 2021

AbstractAmyloid fibrils are abnormal protein aggregates that relate to a large number of amyloidoses and neurodegenerative diseases. The oligomeric precursors, or prefibrillar intermediates, which emerge prior to the amyloid fibril formation, have been known to play a crucial role for the formation. Therefore, it is essential to elucidate the mechanisms of the structural development of the prefibrillar intermediates and ways to prevent its fibril formation. An insulin-derived peptide, insulin B chain, has been known for its stable accumulation of the prefibrillar intermediates. In this study, structural development of B chain prefibrillar intermediates was monitored by transmission electron microscopy and small-angle X-ray scattering combined with size exclusion chromatography and solid-state NMR spectroscopy to elucidate the stability and secondary structure. We further tracked its inhibition process by fibrinogen (Fg), which has been known to effectively prevent the amyloid fibril formation of B chain. We demonstrated that prefibrillar intermediates are wavy structures with low β-sheet content, growing in a multistep manner toward the nucleation for the amyloid fibril formation. In the presence of Fg, the formation of the prefibrillar intermediates slowed down by forming specific complexes. These observations suggest that the prefibrillar intermediates serve as reaction fields for the nucleation and its propagation for the amyloid fibril formation, whereas the inhibition of prefibrillar intermediate elongation by Fg is the significant factor to suppress the fibril formation. We propose that the obtained molecular picture could be a general inhibition mechanism of the amyloid fibril formation by the inhibitors.
SARS-CoV-2 Omicron VOC Transmission in Danish Households
Authors: Lyngse Frederik Plesner , Mortensen Laust Hvas , Denwood Matthew J. , Christiansen Lasse Engbo , Møller Camilla Holten , Skov Robert Leo , Spiess Katja , Fomsgaard Anders , Lassaunière Maria Magdalena , Rasmussen Morten , Stegger Marc , Nielsen Claus , Sieber Raphael Niklaus , Cohen Arieh Sierra , Møller Frederik Trier , Overvad Maria , Mølbak Kåre , Krause Tyra Grove , Kirkeby Carsten Thure 
Published: December 2021

1AbstractThe Omicron variant of concern (VOC) is a rapidly spreading variant of SARS-CoV-2 that is likely to overtake the previously dominant Delta VOC in many countries by the end of 2021.We estimated the transmission dynamics following the spread of Omicron VOC within Danish households during December 2021. We used data from Danish registers to estimate the household secondary attack rate (SAR).Among 11,937 households (2,225 with the Omicron VOC), we identified 6,397 secondary infections during a 1-7 day follow-up period. The SAR was 31% and 21% in households with the Omicron and Delta VOC, respectively. We found an increased transmission for unvaccinated individuals, and a reduced transmission for booster-vaccinated individuals, compared to fully vaccinated individuals. Comparing households infected with the Omicron to Delta VOC, we found an 1.17 (95%-CI: 0.99-1.38) times higher SAR for unvaccinated, 2.61 times (95%-CI: 2.34-2.90) higher for fully vaccinated and 3.66 (95%-CI: 2.65-5.05) times higher for booster-vaccinated individuals, demonstrating strong evidence of immune evasiveness of the Omicron VOC.Our findings confirm that the rapid spread of the Omicron VOC primarily can be ascribed to the immune evasiveness rather than an inherent increase in the basic transmissibility.
Prenatal immune stress induces a prolonged blunting of microglia activation that impacts striatal connectivity
Authors: Hayes Lindsay N. , An Kyongman , Carloni Elisa , Li Fangze , Vincent Elizabeth , Paranjpe Manish , Dölen Gül , Goff Loyal A. , Ramos Adriana , Kano Shin-ichi , Sawa Akira 
Published: December 2021

AbstractRecent studies suggested that microglia, the primary brain immune cells, can affect circuit connectivity and neuronal function1–3. Microglia infiltrate the neuroepithelium early in embryonic development and are maintained in the brain throughout adulthood4,5. Several maternal environmental factors, such as aberrant microbiome, immune activation, and poor nutrition, can influence prenatal brain development6–8. Nevertheless, it is unknown how changes in the prenatal environment instruct the developmental trajectory of infiltrating microglia, which in turn affect brain development and function. Here we show that after maternal immune activation (MIA) microglia from the offspring have a long-lived decrease in immune reactivity (blunting) across the developmental trajectory. The blunted immune response was concomitant with changes in the chromatin accessibility and reduced transcription factor occupancy of the open chromatin. Single cell RNA sequencing revealed that MIA does not induce a distinct subpopulation but rather decreases the contribution to inflammatory microglia states. Prenatal replacement of MIA microglia with physiological infiltration of naïve microglia ameliorated the immune blunting and restored a decrease in presynaptic vesicle release probability onto dopamine receptor type-two medium spiny neurons, indicating that aberrantly formed microglia due to an adverse prenatal environment impacts the long-term microglia reactivity and proper striatal circuit development.
Revisiting rustrela virus – new cases of encephalitis and a solution to the capsid enigma
Authors: Pfaff Florian , Breithaupt Angele , Rubbenstroth Dennis , Nippert Sina , Baumbach Christina , Gerst Sascha , Langner Christoph , Wylezich Claudia , Ebinger Arnt , Höper Dirk , Ulrich Rainer G. , Beer Martin 
Published: December 2021

AbstractRustrela virus (RusV, species Rubivirus strelense) is a recently discovered relative of rubella virus (RuV) that has been detected in cases of encephalitis across a wide spectrum of mammals, including placental and marsupial animals. Here we diagnosed two additional cases of fatal RusV-associated meningoencephalitis in a South American coati (Nasua nasua) and a Eurasian otter (Lutra lutra) that were detected in a zoological garden with history of prior RusV infections. Both animals showed abnormal movement or unusual behaviour and their brains tested positive for RusV using specific RT-qPCR and RNA in situ hybridization. As previous sequencing of RusV proved to be very challenging, we employed a sophisticated target-specific capture enrichment with specifically designed RNA baits to generate complete RusV genome sequences from both detected encephalitic animals and apparently healthy wild yellow-necked field mice (Apodemus flavicollis). Furthermore, the technique was used to revise three previously published RusV genomes from two encephalitic animals and a wild yellow-necked field mouse. Virus-to-host sequence ratio and thereby sequence coverage improved markedly using the enrichment method as compared to standard procedures. When comparing the newly generated RusV sequences to the previously published RusV genomes, we identified a previously undetected stretch of 309 nucleotides predicted to represent the intergenic region and the sequence encoding the N-terminus of the capsid protein. This indicated that the original RusV sequence was likely incomplete due to misassembly of the genome at a region with an exceptionally high G+C content of >80 mol%, which could not be resolved even by enormous sequencing efforts with standard methods. The updated capsid protein amino acid sequence now resembles those of RuV and ruhugu virus in size and harbours a predicted RNA binding domain that was not encoded in the original RusV genome version. The new sequence data indicate that RusV has the largest overall genome (9,631 nucleotides), intergenic region (290 nucleotides) and capsid protein-encoding sequence (331 codons) within the genus Rubivirus.
Denitrification in foraminifera has ancient origin and is complemented by associated bacteria
Authors: Woehle Christian , Roy Alexandra-Sophie , Glock Nicolaas , Michels Jan , Wein Tanita , Weissenbach Julia , Romero Dennis , Hiebenthal Claas , Gorb Stanislav N. , Schönfeld Joachim , Dagan Tal 
Published: December 2021

AbstractBenthic foraminifera are unicellular eukaryotes that inhabit sediments of aquatic environments. Several foraminifera of the order Rotaliida are known to store and use nitrate for denitrification, a unique energy metabolism among eukaryotes. The rotaliid Globobulimina spp. has been shown to encode an incomplete denitrification pathway of bacterial origin. However, the prevalence of denitrification genes in foraminifera remains unknown and the missing denitrification pathway components are elusive. Analysing transcriptomes and metagenomes of ten foraminiferal species from the Peruvian oxygen minimum zone, we show that denitrification genes are highly conserved in foraminifera. We infer of the last common ancestor of denitrifying foraminifera, which enables us to predict the ability to denitrify for additional foraminiferal species. Additionally, an examination of the foraminiferal microbiota reveals evidence for a stable interaction with Desulfobacteracea, which harbour genes that complement the foraminiferal denitrification pathway. Our results provide evidence that foraminiferal denitrification is complemented by the foraminifera-associated microbiome. The interaction of foraminifera with their resident bacteria is at the basis of foraminiferal adaptation to anaerobic environments that manifested in ecological success within oxygen depleted habitats.Significance StatementA substantial component of the global nitrogen cycle is the production of biologically inaccessible dinitrogen attributed to anaerobic denitrification by prokaryotes. Recent evidence identified a eukaryote – foraminifera – as new key players in this ‘loss’ of bioavailable nitrogen. The evolution of denitrification in eukaryotes constitutes a rare event and the genetic mechanisms of the denitrification pathway in foraminifera are just starting to be elucidated. We present large-scale sequencing analyses of ten denitrifying foraminiferal species, which reveals the high conservation of the foraminiferal denitrification pathway. We further find evidence for a complementation of denitrification by the foraminiferal microbiome. Together, these findings provide novel insights on the early evolution of a previously overlooked component in the marine nitrogen cycle.
Properties and computational consequences of fast dendritic spikes during natural behavior
Authors: Destexhe Alain , Mehta Mayank 
Published: December 2021

AbstractDendritic membrane potential was recently measured for the first time in drug-free, naturally behaving rats over several days. These showed that neuronal dendrites generate a lot of sodium spikes, up to ten times as many as the somatic spikes. These key experimental findings are reviewed here, along with a discussion of computational models, and computational consequences of such intense spike traffic in dendrites. We overview the experimental techniques that enabled these measurements as well as a variety of models, ranging from conceptual models to detailed biophysical models. The biophysical models suggest that the intense dendritic spiking activity can arise from the biophysical properties of the dendritic voltage-dependent and synaptic ion channels, and delineate some computational consequences of fast dendritic spike activity. One remarkable aspect is that in the model, with fast dendritic spikes, the efficacy of synaptic strength in terms of driving the somatic activity is much less dependent on the position of the synapse in dendrites. This property suggests that fast dendritic spikes is a way to confer to neurons the possibility to grow complex dendritic trees with little computational loss for the distal most synapses, and thus form very complex networks with high density of connections, such as typically in the human brain. Another important consequence is that dendritically localized spikes can allow simultaneous but different computations on different dendritic branches, thereby greatly increasing the computational capacity and complexity of neuronal networks.
Estimation of the biosorption potential of certain representatives of the genus Bacillus in interaction with lead cation in vitro
Authors: Sizentsov A.N. , Galaktionova L.V. , Davydova O.K. , Nikiyan A.N. , Sizentsov Ya.A. 
Published: December 2021

ABSTRACTThe article presents data on the physicochemical and metabolically dependent mechanisms of detoxification by microorganisms of heavy metals that enter the environment during anthropogenic pollution. The taxonomic and physiological-biochemical diversity of microorganisms capable of neutralizing toxicants has been demonstrated. In the experimental part of the study, the combination of the methods used made it possible to fully assess the degree of toxicity and the effect of lead cations on the growth of bacteria of the genus Bacillus in a model experiment. Thus, the use of atomic absorption spectrophotometry and atomic force microscopy gave an idea of the level of biosorption of a given xenobiotic element from a substrate with localization of inactive forms of lead. The data obtained indicate the presence of an inhibitory effect of Pb(NO3)2 and Pb(CH3COO)2 in concentrations from 1 mM to 0.063 mM about the test organisms under study. The presence of cations with a nutrient substrate gives a false-positive idea of the degree of influence of lead on the growth of the studied microorganisms, since an increase in optical density in test samples is due to high sorption characteristics and, as a consequence, is characterized by an increase in relative optical density. An assessment of the detoxification mechanisms, which is expressed by active bioaccumulation of lead on the surface elements of the microbial cell up to 65% at the point of entering the stationary growth phase, indicates the promising use of representatives of this group of microorganisms as microbial bioremediation and correctors of excess content of this element in the body or ecosystem as a whole.
Revealing the secrets beneath grapevine and Plasmopara viticola early communication: a picture of host and pathogen proteomes
Authors: Figueiredo Joana , Santos Rita B. , Guerra-Guimarães Leonor , Leclercq Céline C. , Renaut Jenny , Sousa Lisete , Figueiredo Andreia 
Published: December 2021

AbstractPlant apoplast is the first hub of plant-pathogen communication where pathogen effectors are recognized by plant defensive proteins and cell receptors and several signal transduction pathways are activated. As a result of this first contact, the host triggers a defence response that involves the modulation of several extra and intracellular proteins. In grapevine-pathogen interactions, little is known about the communication between cells and apoplast. Also, the role of apoplastic proteins in response to pathogens still remains a blackbox. In this study we focused on the first 6 hours after Plasmopara viticola inoculation to evaluate grapevine proteome modulation in the apoplastic fluid (APF) and whole leaf tissue. Plasmopara viticola proteome was also assessed enabling a deeper understanding of plant and pathogen communication. Our results showed that oomycete recognition, plant cell wall modifications, ROS signalling and disruption of oomycete structures are triggered in Regent after P. viticola inoculation. Our results highlight a strict relation between the apoplastic pathways modulated and the proteins identified in the whole leaf proteome. On the other hand, P. viticola proteins related to growth/morphogenesis and virulence mechanisms were the most predominant. This pioneer study highlights the early dynamics of extra and intracellular communication in grapevine defence activation that leads to the successful establishment of an incompatible interaction.
Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern
Authors: Vangeel Laura , Chiu Winston , De Jonghe Steven , Maes Piet , Slechten Bram , Raymenants Joren , André Emmanuel , Leyssen Pieter , Neyts Johan , Jochmans Dirk 
Published: December 2021

AbstractWe assessed the in vitro antiviral activity of remdesivir and its parent nucleoside GS-441524, molnupiravir and its parent nucleoside EIDD-1931 and the viral protease inhibitor nirmatrelvir against the ancestral SARS-CoV2 strain and the five variants of concern including Omicron. VeroE6-GFP cells were pre-treated overnight with serial dilutions of the compounds before infection. The GFP signal was determined by high-content imaging on day 4 post-infection. All molecules have equipotent antiviral activity against the ancestral virus and the VOCs Alpha, Beta, Gamma, Delta and Omicron. These findings are in line with the observation that the target proteins of these antivirals (respectively the viral RNA dependent RNA polymerase and the viral main protease Mpro) are highly conserved.
Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529
Authors: Zhou Tongqing , Wang Lingshu , Misasi John , Pegu Amarendra , Zhang Yi , Harris Darcy R. , Olia Adam S. , Talana Chloe Adrienna , Yang Eun Sung , Chen Man , Choe Misook , Shi Wei , Teng I-Ting , Creanga Adrian , Jenkins Claudia , Leung Kwanyee , Liu Tracy , Stancofski Erik-Stephane D. , Stephens Tyler , Zhang Baoshan , Tsybovsky Yaroslav , Graham Barney S. , Mascola John R. , Sullivan Nancy J. , Kwong Peter D. 
Published: December 2021

AbstractWith B.1.1.529 SARS-CoV-2 variant’s rapid spread and substantially increased resistance to neutralization by vaccinee and convalescent sera, monoclonal antibodies with potent neutralization are eagerly sought. To provide insight into effective neutralization, we determined cryo-EM structures and evaluated potent receptor-binding domain (RBD) antibodies for their ability to bind and neutralize this new variant. B.1.1.529 RBD mutations altered 16% of the RBD surface, clustering on a ridge of this domain proximal to the ACE2-binding surface and reducing binding of most antibodies. Significant inhibitory activity was retained, however, by select monoclonal antibodies including A19-58.1, B1-182.1, COV2-2196, S2E12, A19-46.1, S309 and LY-CoV1404, which accommodated these changes and neutralized B.1.1.529 with IC50s between 5.1-281 ng/ml, and we identified combinations of antibodies with potent synergistic neutralization. Structure-function analyses delineated the impact of resistance mutations and revealed structural mechanisms for maintenance of potent neutralization against emerging variants.Summary SentenceWe show potent B.1.1.529 neutralization by select antibodies and use EM structures to reveal how potency can be retained.