bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulus-dependent depth constancy during head tilt
Authors: Skerswetat Jan , Caoli Andrea , Bex Peter 
Published: March 2022

AbstractStereopsis is traditionally measured with noise-based stereo tests while the observer views the test in primary gaze. We investigated the effect of stimulus sparseness and axial variations of interocular disparity induced via head rotations.First, we measured stereoacuity using a 4-Alternative-Forced-Choice (4-AFC) task with three uncrossed and one crossed disparity bandpass-filtered circles on a passive-3-D-monitor. Ten binocularly-normal adults fixated a central cross and clicked on the circle withcrossed disparity for forty trials/condition. Observers adopted head tilts of 0° or ±20° pitch, roll, or yaw, enforced with an innertial measurement unit and fixation enforced with an eye tracker. Next, we measured stereoacuity in 8 adults while either the head (H), monitor (M), or both (B) were tilted 0°, ±22.5°, or ±45° roll in random order (eighty trials/condition) using a 4-AFC task and random-dot stimuli. Head tilts did not signifcantly alter stereoacuity using narrow-band stimuli(p>0.05), despite that IPDs and the axis of disparity were differentially affected by the tilts. However, for random dot stimuli, stereoacuity decreased with increasing orientation difference between the head and monitor (H and M: p<0.05; B: p>0.05].Head tilt decreases IPD and rotates the axis of interocular disparity, however, these manipulations affect stereoacuity when measured with noise stimuli but not with sparse stimuli. The results are consistent with a vestibular input to stereoscopic disparity processing that can be detected by sparse stimuli but is masked by dense stimuli. The results have implications for natural vision and for clinical screening in patients with abnormal head posture.Significance statementDepth perception is a critical feature of human vision and it is thought that the ability to perceive stereoscopic depth is bound to an essentially eye-fixed, horizontal disparity of each image that rapidly deteriorates away from that limited horizontal axis. In a set of head tilt experiments, we varied the orientations of stereoscopic images and demonstrate that stereoacuity remains constant when deploying sparse narrow-band stimuli, and only worsens when using fine-detailed noise stimuli that mask off-axis disparities. These results shine new light upon the debate of neuroplasticity of stereo vision. Moreover, the results are consequential for diagnosis and treatment in people with atypical head- and eye alignment, such as for patients with torticollis or strabismus.
Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis
Authors: Wills Nicola K , Nair Nikhil , Patel Kashyap , Sikder Omaike , Adriaanse Marguerite , Eikelboom John , Wasserman Sean 
Published: March 2022

AbstractBackgroundRandomised controlled trials (RCTs) have reported inconsistent effects from intensified anticoagulation on clinical outcomes in Covid-19. We performed an aggregate data meta-analysis from available trials to quantify effect on non-fatal and fatal outcomes and identify subgroups who may benefit.MethodsWe searched multiple databases for RCTs comparing intensified (intermediate or therapeutic dose) versus standard prophylactic dose anticoagulation in adults with laboratory-confirmed Covid-19 through 19 January 2022. The primary efficacy outcome was all-cause mortality at end of follow-up or discharge. We used random effects meta-analysis to estimate pooled risk ratios for mortality, thrombotic, and bleeding events, and performed subgroup analysis for clinical setting and dose of intensified anticoagulation.ResultsEleven RCTs were included (n = 5873). Intensified anticoagulation was not associated with a reduction in mortality for up to 45 days compared with prophylactic anticoagulation: 17.5% (501/2861) died in the intensified anticoagulation group and 18.8% (513/2734) died in the prophylactic anticoagulation group, relative risk (RR) 0.93; 95%CI, 0.79 – 1.10. On subgroup analysis, there was a possible signal of mortality reduction for inpatients admitted to general wards, although with low precision and high heterogeneity (5 studies; RR 0.84; 95% CI, 0.49 - 1.44; I2 = 75%) and not significantly different to studies performed in the ICU (interaction P = 0.51). Risk of venous thromboembolism was reduced with intensified anticoagulation compared with prophylaxis (8 studies; RR 0.53, 95%CI 0.41 – 0.69; I2 = 0%). This effect was driven by therapeutic rather than intermediate dosing on subgroup analysis (interaction P =0.04). Major bleeding was increased with use of intensified anticoagulation (RR 1.73, 95% CI 1.17 – 2.56) with no interaction for dosing and clinical setting.ConclusionIntensified anticoagulation has no effect on short term mortality among hospitalised adults with Covid-19 and is associated with increased risk of bleeding. The observed reduction in venous thromboembolism risk and trend towards reduced mortality in non-ICU hospitalised patients requires exploration in additional RCTs.SummaryIn this aggregate data meta-analysis, use of intensified anticoagulation had no effect on short term mortality among hospitalised adults with Covid-19 and was associated with increased risk of bleeding.
Angiotensin converting enzyme 2 (ACE2): Virus accomplice or host defender
Authors: Wang Jiyan , Chang Hongkai , Qiao Yaya , Sun Huanran , Li Xichuan , Yuan Shuofeng , Zhang Shuai , Shan Changliang 
Published: March 2022

ABSTRACTThe current coronavirus disease-19 (COVID-19) caused by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has seriously disrupted the daily life of human, mainly attributed to the fact that we know too little about SARS-CoV-2. Increasing studies show that viral infection alters host cells glucose metabolism, which is crucial for viral nucleic acid replication. Here, we integrated RNA-sequencing results and found that SARS-CoV-2 infection alters the aerobic glycolysis, pentose phosphate pathway (oxiPPP), and DNA replication in lung tissues and cells. However, the direction of metabolic flux and DNA replication were dominated by angiotensin-converting enzyme 2 (ACE2), a host cell-expressed viral receptor protein. More interesting, although hosts with high expression of ACE2 are more likely to be infected with SARS-CoV-2, the invading virus cannot perform nucleic acid replication well due to the restriction of glucose metabolism, and eventually resulting prolonged infection-cycle or infection failure. Our findings, after a typical epidemiological investigation and modeling analysis, preliminarily explain the reasons for the emergence of asymptomatic infections or lower copy virus at early stage in host with higher ACE2 levels, which will provide important help for the development of more accurate and effective detection methods for diagnosing COVID-19.Graphical abstract
Belgian endive-derived biostimulants promote shoot and root growth in vitro
Authors: Ogunsanya Halimat Yewande , Motti Pierfrancesco , Li Jing , Trinh Hoang Khai , Xu Lin , Bernaert Nathalie , Van Droogenbroeck Bart , Murvanidze Nino , Werbrouck Stefaan , Mangelinckx Sven , Ramirez Aldana , Geelen Danny 
Published: March 2022

AbstractRecovering biostimulant compounds from by-products of crops is a promising strategy to add value, enhance sustainability, and increase the environmental safety of the agricultural production chain. Here, we report consistent root and shoot growth-stimulating bioactivity present in water-based extracts from Belgian endive forced roots (Cichorium intybus var. foliosum) over two consecutive harvest years. The shoot and the primary root of in vitro cultivated Arabidopsis thaliana treated with Belgian endive extract were about 30% increased in size compared to plants grown under control conditions. The ornamental species Plectranthus esculentus also showed enhanced in vitro shoot and root growth, suggesting bioactivity on a broad range of species. Fractionation of the Belgian endive extracts into aqueous and organic subfractions coupled with bio-activity measurements showed that the principal root and shoot growth-promoting ingredients are primarily water-soluble. NMR-based characterization of the bioactive aqueous fractions revealed the presence of pre-dominantly sugars and organic acids. Malate and sugars were abundant and common to all water fractions, suggesting these molecules contributed to the growth stimulation phenotype. The findings indicate that Belgian endive roots are a source for the development of organic waste-derived biostimulants with potential for application in tissue culture and putatively for soil-grown crop production.
A short ERAP2 that binds IRAP is expressed in macrophages independently from gene variation
Authors: Mattorre Benedetta , Caristi Silvana , Donato Simona , Volpe Emilia , Faiella Marika , Paiardini Alessandro , Sorrentino Rosa , Paladini Fabiana 
Published: March 2022

AbstractThe M1 zinc metalloproteases ERAP1, ERAP2 and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have been also entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents in which the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independently from the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic microenvironment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt to reconsider the role of ERAP2 which might have been maintained in humans because fulfilling a relevant function as “short” form in specialized cells.
Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
Authors: Correia-Melo Clara , Kamrad Stephan , Messner Christoph B. , Tengölics Roland , Herrera-Dominguez Lucía , Townsend St John , Alam Mohammad Tauqeer , Freiwald Anja , Campbell Kate , Aulakh Simran , Szyrwiel Lukasz , Yu Jason S. L. , Zelezniak Aleksej , Demichev Vadim , Muelleder Michael , Papp Balázs , Ralser Markus 
Published: March 2022

AbstractMetabolism is fundamentally intertwined with the ageing process. We here report that a key determinant of cellular lifespan is not only nutrient supply and intracellular metabolism, but also metabolite exchange interactions that occur between cells. Studying chronological ageing in yeast, we observed that metabolites exported by young, exponentially growing, cells are re- imported during the stationary phase when cells age chronologically, indicating the existence of cross-generational metabolic interactions. We then used self-establishing metabolically cooperating communities (SeMeCos) to boost cell-cell metabolic interactions and observed a significant lifespan extension. A search for the underlying mechanisms, coupling SeMeCos, metabolic profiling, proteomics and genome-scale metabolic modelling, attributed a specific role to methionine consumer cells. These cells were enriched over time, adopted glycolytic metabolism and increased export of protective metabolites. Glycerol, in particular, accumulated in the communal metabolic environment and extended the lifespan of all cells in the community in a paracrine fashion. Our results hence establish metabolite exchange interactions as a determinant of the ageing process and show that metabolically cooperating cells shape their metabolic environment to achieve lifespan extension.
Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia
Authors: Koch Elise , Kauppi Karolina , Chen Chi-Hua 
Published: March 2022

AbstractIn the protein-protein interactome, we have previously identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance. Here, we further studied this overlap to identify potential candidate drugs for repurposing to treat the cognitive symptoms in schizophrenia. We first defined a cognition-related schizophrenia interactome from network propagation analyses, and identified drugs known to target more than one protein within this network. Thereafter, we used gene expression data to further select drugs that could counteract schizophrenia-associated gene expression perturbations. Additionally, we stratified these analyses by sex to identify sex-specific pharmacological treatment options for the cognitive symptoms in schizophrenia. After excluding drugs contraindicated in schizophrenia, we identified eight drug candidates, most of which have anti-inflammatory and neuroprotective effects. Due to gene expression differences in male and female patients, four of those drugs were also selected in our male-specific analyses, and the other four in the female-specific analyses. Based on our bioinformatics analyses of disease genetics, we suggest eight candidate drugs that warrant further examination for repurposing to treat the cognitive symptoms in schizophrenia, and suggest that these symptoms could be addressed by sex-specific pharmacological treatment options.
Surface interaction patches link non-specific binding and phase separation of antibodies
Authors: Ausserwöger Hannes , Krainer Georg , Welsh Timothy J. , Sneideris Tomas , Schneider Matthias M. , Invernizzi Gaetano , Herling Therese W. , Lorenzen Nikolai , Knowles Tuomas P. J. 
Published: March 2022

AbstractNon-specificity is a key challenge in the successful development of therapeutic antibodies. The tendency for non-specific binding in antibodies is often difficult to reduce via judicious design and, instead, it is necessary to rely on comprehensive screening campaigns. A better understanding of the molecular origins that drive antibody non-specificity is therefore highly desirable in order to prevent non-specific off-target binding. Here, we perform a systematic analysis of the impact of surface patch properties on antibody non-specificity using a designer antibody library as a model system and DNA as a non-specificity ligand. Using an in solution microfluidics approach, we discover patches of surface hydrogen bonding to be causative of the observed non-specificity under physiological salt conditions and suggest them to be a vital addition to the molecular origins of non-specificity. Moreover, we find that a change in formulation conditions leads to DNA-induced antibody liquid–liquid phase separation as a manifestation of antibody non-specificity. We show that this behaviour is driven by a cooperative electrostatic network assembly mechanism enabled by mutations that yield a positively charged surface patch. Together, our study provides a direct link between molecular binding events and macroscopic liquid–liquid phase separation. These findings highlight a delicate balance between surface interaction patches and their crucial role in conferring antibody non-specificity.
Global phylogeography of marine Synechococcus in coastal areas reveals strikingly different communities than in the open ocean
Authors: Doré Hugo , Leconte Jade , Guyet Ulysse , Breton Solène , Farrant Gregory K. , Demory David , Ratin Morgane , Hoebeke Mark , Corre Erwan , Pitt Frances D. , Ostrowski Martin , Scanlan David J. , Partensky Frédéric , Six Christophe , Garczarek Laurence 
Published: March 2022

AbstractMarine Synechococcus comprise a numerically and ecologically prominent phytoplankton group, playing a major role in both carbon cycling and trophic networks in all oceanic regions except in the polar oceans. Despite their high abundance in coastal areas, our knowledge of Synechococcus communities in these environments is based on only a few local studies. Here, we use the global metagenome dataset of the Ocean Sampling Day (June 21st 2014) to get a snapshot of the taxonomic composition of coastal Synechococcus communities worldwide, by recruitment on a reference database of 141 picocyanobacterial genomes, representative of the whole Prochlorococcus, Synechococcus and Cyanobium diversity. This allowed us to unravel drastic community shifts over small to medium scale gradients of environmental factors, in particular along European coasts. The combined analysis of the phylogeography of natural populations and the thermophysiological characterization of eight strains, representative of the four major Synechococcus lineages (clades I to IV), also brought novel insights about the differential niche partitioning of clades I and IV, which most often co-dominate the Synechococcus community in cold and temperate coastal areas. Altogether, this study tackles the main differences between open-ocean and coastal communities worldwide.
Excitatory and inhibitory D-serine binding to the NMDA receptor
Authors: Yovanno Remy A. , Chou Tsung Han , Brantley Sarah J. , Furukawa Hiro , Lau Albert Y. 
Published: March 2022

ABSTRACTN-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. D-serine and glycine bind to one subunit, GluN1, while glutamate binds to the other, GluN2. These agonists bind to the receptor’s bi-lobed ligand-binding domains (LBDs), which close around the agonist during receptor activation. To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. Surprisingly, we observed D-serine binding to both GluN1 and GluN2A LBDs, suggesting that D-serine competes with glutamate for binding to GluN2A. This mechanism is confirmed by our electrophysiology experiments, which show that D-serine is indeed inhibitory at high concentrations. Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. We developed a workflow using pathway similarity analysis to identify groups of residues working together to promote binding. These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD.
E. coli can eat DNA as excellent nitrogen source to grow quickly
Authors: Huang Lili , Zhang Yehui , Du Xinmei , An Ran , Liang Xingguo 
Published: March 2022

AbstractIs DNA or RNA a good nutrient? Although scientists have raised this question for dozens of years, few textbooks mention the nutritional role of nucleic acids. Paradoxically, mononucleotides are widely added to infant formula milk and animal feed for improving Intestinal health. Here, found that E. coli can grow well in the medium with DNA as carbon and nitrogen sources. More interestingly, in the presence of glucose and DNA, bacteria grew more rapidly, showing that bacteria can use DNA as an excellent nitrogen source. Surprisingly, the amount of DNA in culture media decreased but its length remained unchanged, demonstrating that E. coli ingested long DNA directly. The gene expression study shows that E. coli mainly ingests DNA before digestion and digests it in the periplasm. Bifidobacterium bifidum can also use DNA as the nitrogen source for growth but not efficiently as E. coli. This study is of great significance to study DNA metabolism and utilization in organisms. It also lays a foundation to understand the nutritional function of DNA for intestinal flora and human health.
Attenuation of a DNA Cruciform by a Conserved Regulator Directs T3SS-1 mediated virulence in Vibrio parahaemolyticus
Authors: Getz Landon J. , Brown Justin M. , Sobot Lauren , Chow Alexandra , Mahendrarajah Jastina , Thomas Nikhil A. 
Published: March 2022

AbstractPathogenic Vibrio species account for 3-5 million annual life-threatening human infections. Virulence is driven by bacterial hemolysin and toxin gene expression often positively regulated by the winged helix-turn-helix (wHTH) HlyU transcriptional regulator family and silenced by Histone-like nucleoid structural protein (H-NS). In the case of Vibrio parahaemolyticus, HlyU is required for virulence gene expression associated with Type 3 Secretion System-1 (T3SS-1) although its mechanism of action is not understood. Here, we provide evidence for DNA cruciform attenuation mediated by HlyU binding to support concomitant virulence gene expression. Genetic and biochemical experiments revealed that upon HlyU mediated DNA cruciform attenuation, an intergenic cryptic promoter became accessible allowing for exsA mRNA expression and initiation of an ExsA autoactivation feedback loop at a separate ExsA-dependent promoter. Using a heterologous E. coli expression system, we reconstituted the dual promoter elements which revealed that HlyU binding and DNA cruciform attenuation were strictly required to initiate the ExsA autoactivation loop. The data indicate that HlyU acts to attenuate a transcriptional repressive DNA cruciform to support T3SS-1 virulence gene expression and reveals a non-canonical extricating gene regulation mechanism in pathogenic Vibrio species.
Comparing lipid remodeling in mouse adipose and liver tissue with quantitative Raman microscopy
Authors: Paul Alexandra , Chanclón Belén , Brännmark Cecilia , Wittung-Stafshede Pernilla , Olofsson Charlotta S. , Asterholm Ingrid Wernstedt , Parekh Sapun H. 
Published: March 2022

ABSTRACTBrown adipose tissue (BAT) consists of highly metabolically active adipocytes that catabolize nutrients to produce heat. Playing an active role in triacylglycerol (TAG) clearance, research has shown that dietary fatty acids can modulate the TAG chemistry deposition in BAT after weeks-long dietary intervention, similar to what has been shown in white adipose tissue (WAT). Our objective was to compare the influence of sustained, non-chronic dietary intervention (a one-week interval) on WAT and BAT lipid metabolism and deposition in situ. We use quantitative, label-free chemical microscopy to show that one week of HFD intervention results in dramatically larger lipid droplet (LD) growth in BAT (and liver) compared to LD growth in inguinal WAT (IWAT). Moreover, BAT showed lipid remodeling as increased unsaturated TAGs in LDs, resembling the dietary lipid composition, while WAT (and liver) did not show lipid remodeling on this time scale. Concurrently, expression of genes involved in lipid metabolism, particularly desaturases, was reduced in BAT and liver from HFD-fed mice after one week. Our data show that BAT lipid chemistry remodels exceptionally fast to dietary lipid intervention compared WAT, which further points towards a role in TAG clearance.