bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust IgM responses following intravenous vaccination with Bacille Calmette–Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques
Authors: Irvine Edward B. , O’Neil Anthony , Darrah Patricia A. , Shin Sally , Choudhary Alok , Li Wenjun , Honnen William , Mehra Smriti , Kaushal Deepak , Gideon Hannah Priyadarshini , Flynn JoAnne L. , Roederer Mario , Seder Robert A. , Pinter Abraham , Fortune Sarah , Alter Galit 
Published: November 2021

AbstractDevelopment of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection againstMycobacterium tuberculosis(Mtb). Intravenous (i.v.) vaccination with Bacille Calmette–Guérin (BCG) provides nearly complete protection against TB in rhesus macaques, but the antibody response it elicits remains incompletely defined. Here we show that i.v. BCG drives superior antibody responses in the plasma and the lungs of rhesus macaques compared to traditional intradermal BCG administration. While i.v. BCG broadly expands antibody titers and functions, IgM titers in the plasma and lungs of immunized macaques are among the strongest markers of reduced bacterial burden. IgM was also enriched in macaques that received protective vaccination with an attenuated strain ofMtb. Finally, anMtb-specific IgM monoclonal antibody reducedMtbsurvival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and mediator of protection against TB.
Structure of the human SAGA coactivator complex
Authors: Herbst Dominik A. , Esbin Meagan N. , Louder Robert K. , Dugast-Darzacq Claire , Dailey Gina M. , Fang Qianglin , Darzacq Xavier , Tjian Robert , Nogales Eva 
Published: November 2021

AbstractThe SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP6) binding site in TRRAP and an unusual property of its pseudo-(Ψ)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer.
Simple yet effective methods to probe hydrogel stiffness for mechanobiology
Authors: Gandin Alessandro , Murugesan Yaswanth , Torresan Veronica , Ulliana Lorenzo , Citron Anna , Contessotto Paolo , Battilana Giusy , Panciera Tito , Ventre Maurizio , Netti A. Paolo , Nicola Lucia , Piccolo Stefano , Brusatin Giovanna 
Published: November 2021

AbstractIn spite of tremendous advances made in the comprehension of mechanotransduction, implementation of mechanobiology assays remains challenging for the broad community of cell biologists. Hydrogel substrates with tunable stiffness are essential tool in mechanobiology, allowing to investigate the effects of mechanical signals on cell behavior. A bottleneck that slows down the popularization of hydrogel formulations for mechanobiology is the assessment of their stiffness, typically requiring expensive and sophisticated methodologies in the domain of material science. Here we overcome such barriers offering the reader protocols to set-up and interpret two straightforward, low cost and high-throughput tools to measure hydrogel stiffness: static macroindentation and micropipette aspiration. We advanced on how to build up these tools and on the underlying theoretical modeling. Specifically, we validated our tools by comparing them with leading techniques used for measuring hydrogel stiffness (atomic force microscopy, uniaxial compression and rheometric analysis) with consistent results on PAA hydrogels or their modification. In so doing, we also took advantage of YAP/TAZ nuclear localization as biologically validated and sensitive readers of mechanosensing, all in all presenting a suite of biologically and theoretically proven protocols to be implemented in most biological laboratories to approach mechanobiology.
Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
Authors: Lucchetti Donatella , Zurlo Ina Valeria , Colella Filomena , Ricciardi-Tenore Claudio , Di Salvatore Mariantonietta , Tortora Giampaolo , De Maria Ruggero , Giuliante Felice , Cassano Alessandra , Basso Michele , Crucitti Antonio , Laurenzana Ilaria , Artemi Giulia , Sgambato Alessandro 
Published: November 2021

AbstractLiquid biopsy has become a useful alternative in metastatic colorectal cancer (mCRC) patients when tissue biopsy of metastatic sites is not feasible. In this study we aimed to investigate the clinical utility of circulating exosomes DNA in the management of mCRC patients. Exosomes level and KRAS mutational status in exosomal DNA was assesed in 70 mCRC patients and 29 CRC primary tumor and were analysed at different disease steps evaluating serial blood samples (240 blood samples). There was a significant correlation between the extension of disease and exosomes level and the resection of primary localized tumor was correlated with a decrease of KRAS G12V/ D copies and fractional abundance in metastatic disease. CEA expression and liver metastasis correlated with a higher number of KRAS G12V/D copies/ml and a higher fractional abundance; in the subgroup of mCRC patients eligible for surgery, the size of tumor and the radiological response were related to exosomes level but only the size was related to the number of KRAS WT copies; both KRAS wild-type and mutated levels were identified as a prognostic factor related to OS. Finally, we found that 91% of mutated mCRC patients became wild type after the first line chemotherapy but this status reverted in mutated one at progression in 80% of cases. In a prospective cohort of mCRC patients, we show how longitudinal monitoring using exosome-based liquid biopsy provides clinical information relevant to therapeutic stratification.
Insights into the nutritional properties and microbiome diversity in sweet and sour yogurt manufactured in Bangladesh
Authors: Islam S. M. Rafiqul , Tanzina Afsana Yeasmin , Foysal Md Javed , Hoque M. Nazmul , Rumi Meheadi Hasan , Siddiki A. M. A. M. Zonaed , Tay Alfred Chin-Yen , Hossain M. Jakir , Bakar Muhammad Abu , Mostafa Mohammad , Mannan Adnan 
Published: November 2021

AbstractYogurt is one of the most frequently consumed dairy products for nutritional benefits. Although yogurt is enriched with probiotics, it is susceptible to spoilage because of the presence of pathogenic microbes. Spoiled yogurt if consumed can cause food-borne diseases. This study aimed to assess the nutritional composition and microbiome diversity in yogurt manufactured in Bangladesh. Microbial diversity was analyzed through high-throughput sequencing of bacterial 16S rRNA gene and fungal internal transcribed spacer (ITS) region. From nutritional analysis, significantly (P < 0.05) higher pH, fat, moisture, total solid and solid-non-fat contents (%) were observed in sweet yogurt. Following the classification of Illumina sequences, 84.86% and 72.14% of reads were assigned to bacterial and fungal genera, respectively, with significantly higher taxonomic richness in sour yogurt prepared from buffalo. A significant difference in bacterial (Ppermanova = 0.001) and fungal (Ppermanova = 0.013) diversity between sweet and sour yogurt was recorded. A total of 76 bacterial and 70 fungal genera were detected across these samples which were mostly represented by Firmicutes (92.89%) and Ascomycota (98%) phyla, respectively. This is the first study that accentuates nutritional profiles and microbiome diversity of Bangladeshi yogurt which are crucial in determining both active and passive health effects of yogurt consumption in individuals.
Analysis of risk factors associated with gas embolism and evaluation of predictors of mortality in 482 loggerhead sea turtles
Authors: Franchini D. , Valastro C. , Ciccarelli S. , Trerotoli P. , Paci S. , Caprio F. , Salvemini P. , Lucchetti A. , Di Bello A. 
Published: November 2021

AbstractSea turtles that are entrapped in static and towed nets may develop gas embolism which can lead to severe organ injury and death. Trawling characteristics, physical and physiologic factors associated with gas-embolism and predictors of mortality were analysed from 482 bycaught loggerheads. We found 204 turtles affected by gas-embolism and significant positive correlations between the presence of gas-embolism and duration, depth, ascent rate of trawl, turtle size and temperature, and between mortality and ascent time, neurological deficits, significant acidosis and involvement of > 12 cardiovascular sites and the left atrium and sinus venosus-right atrium. About 90% turtles with GE alive upon arrival at Sea Turtle Clinic recovered from the disease without any supportive drug therapy. Results of this study may be useful in clinical evaluation, prognostication, and management for turtles affected by gas-embolism, but bycatch reduction must become a priority for major international organizations. According to the results of the present study the measures to be considered to reduce the catches or mortality of sea turtles for trawling are to be found in the modification of fishing nets or fishing operations and in greater awareness and education of fishermen.
Triassic hydrothermal chimneys from the Ordos Basin of Northern China
Authors: You Jiyuan , Liu Yiqun , Zhou Dingwu , Yang Yiyao 
Published: November 2021

AbstractBecause few well-preserved hydrothermal chimneys have been found in terrestrial sedimentary rocks, research on paleo-thermal vents in geological history is relatively sparse. In this study, we present our original discovery of “hydrothermal chimneys” from the Chang 7 source rocks of the Triassic Yanchang Formation in the Ordos Basin, China, and provide the best evidence for deciphering hydrothermal activity preserved in the geological record (i.e., sedimentary rocks). Three possible chimney samples (i.e., samples 1551.6, 1551.6–2 and 1574.4) were collected for this study; they were interbedded with mudstones and oil shales, indicative of a deep-lake sedimentary environment. All three samples consist mainly of anhydrite, pyrite, and dolomite with the formation of mineral zoning across the walls of these structures, suggesting a sulfate-dominated stage and a carbonate-sulfide replacement stage. Moreover, their in situ geochemistry is characterized by high Eu, U, Th, Sr, Mn and U/Th ratios, which are typical indicators of hydrothermal vents. In addition, their S isotopes range from 7.89% to 10.88%, near the values of magma sulfur, implying a possible magmatic trigger for these hydrothermal vents. All this evidence shows that the Triassic sedimentary rocks of the Ordos Basin probably contain hydrothermal chimneys. Comparing ancient hydrothermal chimneys to modern hydrothermal chimneys, we should note the important implications of ancient chimneys; their formation mechanism may have been related to oil production, and they are possible indicators for future oil investigations. Further, they have great significance for studying the hydrothermal properties of primary dolomite.
Rapid phenotypic change in a polymorphic salamander over 43 years
Authors: Hantak Maggie M. , Federico Nicholas A. , Blackburn David C. , Guralnick Robert P. 
Published: November 2021

AbstractColor polymorphic animals offer a unique system for studying intraspecific phenotypic responses to climate change. Discrete color morphs are easy to identify, and correlated trait responses of morphs can indicate how climate warming may facilitate long-term maintenance of polymorphisms. We use a historical dataset spanning 43 years to examine temporal shifts in color morph frequency and body size in response to climate in the Eastern Red-backed Salamander,Plethodon cinereus, which contains a widespread striped/unstriped color polymorphism. We created a pipeline to extract high-throughput trait data from fluid-preserved museum specimens where we batch-photographed salamanders, de-aggregated individual specimens from photographs, and solicited help of community scientists to score color morphs. We used a linear modeling framework that includes information about spatial population structure to demonstrate that color morph frequency and body size vary in response to climate, elevation, and over time, with an overall trend of higher frequency and decreased body size of the striped morph, but increased size of the unstriped morph. These surprising results suggest that morphs may be responding to multiple climate and geographic drivers through co-adapted morphological changes. This work highlights new practices of extracting trait data from museum specimens to demonstrate species phenotypes response to climate change.
Assessment of the usefulness of prognostic Van Nuys Prognostic Index in the treatment in ductal carcinoma in situ in 15-year observation
Authors: Kunkiel Michał , Niwińska Anna 
Published: November 2021

AbstractDuctal carcinoma in situ, a marginal fraction of the mammary gland diseases, is recognized in 25% of breast cancers detected with mammographic screening. The aim of the study was to assess the prognostic value of Van Nuys Prognostic Index, serving to determine the method of treatment according to the recurrence risk. From the 737 of cases of DCIS detection patients treated in our department in the years 1996–2011. The remaining 525 patients whose treatment began from excision of local DCIS and whose further course of treatment was determined after histopathological examination, who were left for observation, treated with lumpectomy and radiotherapy or mastectomy, were qualified for the assessment of mentioned index (Online Appendix 1- Figure S1). The 5-, 10- and 15- year disease recurrence-free survival for the group of 525 patients was 88%, 74% and 62%, respectively. The percentage of 5-, 10- and 15-year disease recurrence-free survival in patients treated in compliance with the VNP Index in individual risk groups did not differ in a statistically significant way. In the low-risk group the percentage of recurrences after local excision, after 5, 10 and 15 years of observation amounted to 8.8%, 22.8% and 28.8%. In patients from this group, the recurrence risk after breast conserving treatment and mastectomy was 2% and 0%, respectively. VNP Index is not an optimal tool for patients with DCIS. It can be helpful only in some clinically difficult cases as one of methods of assessing the risk of recurrence.
Determination of probability of causative pathogen in infectious keratitis using deep learning algorithm of slit-lamp images
Authors: Koyama Ayumi , Miyazaki Dai , Nakagawa Yuji , Ayatsuka Yuji , Miyake Hitomi , Ehara Fumie , Sasaki Shin-ichi , Shimizu Yumiko , Inoue Yoshitsugu 
Published: November 2021

AbstractCorneal opacities are important causes of blindness, and their major etiology is infectious keratitis. Slit-lamp examinations are commonly used to determine the causative pathogen; however, their diagnostic accuracy is low even for experienced ophthalmologists. To characterize the “face” of an infected cornea, we have adapted a deep learning architecture used for facial recognition and applied it to determine a probability score for a specific pathogen causing keratitis. To record the diverse features and mitigate the uncertainty, batches of probability scores of 4 serial images taken from many angles or fluorescence staining were learned for score and decision level fusion using a gradient boosting decision tree. A total of 4306 slit-lamp images including 312 images obtained by internet publications on keratitis by bacteria, fungi, acanthamoeba, and herpes simplex virus (HSV) were studied. The created algorithm had a high overall accuracy of diagnosis, e.g., the accuracy/area under the curve for acanthamoeba was 97.9%/0.995, bacteria was 90.7%/0.963, fungi was 95.0%/0.975, and HSV was 92.3%/0.946, by group K-fold validation, and it was robust to even the low resolution web images. We suggest that our hybrid deep learning-based algorithm be used as a simple and accurate method for computer-assisted diagnosis of infectious keratitis.
Inheritance of gene expression throughout fruit development in chili pepper
Authors: Escoto-Sandoval Christian , Ochoa-Alejo Neftalí , Martínez Octavio 
Published: November 2021

AbstractGene expression is the primary molecular phenotype and can be estimated in specific organs or tissues at particular times. Here we analyzed genome-wide inheritance of gene expression in fruits of chili pepper (Capsicum annuumL.) in reciprocal crosses between a domesticated and a wild accession, estimating this parameter during fruit development. We defined a general hierarchical schema to classify gene expression inheritance which can be employed for any quantitative trait. We found that inheritance of gene expression is affected by both, the time of fruit development as well as the direction of the cross, and propose that such variations could be common in many developmental processes. We conclude that classification of inheritance patterns is important to have a better understanding of the mechanisms underlying gene expression regulation, and demonstrate that sets of genes with specific inheritance pattern at particular times of fruit development are enriched in different biological processes, molecular functions and cell components. All curated data and functions for analysis and visualization are publicly available as an R package.
A systematic review and meta-analysis of the association between fluoride exposure and neurological disorders
Authors: Miranda Giza Hellen Nonato , Alvarenga Maria Olímpia Paz , Ferreira Maria Karolina Martins , Puty Bruna , Bittencourt Leonardo Oliveira , Fagundes Nathalia Carolina Fernandes , Pessan Juliano Pelim , Buzalaf Marília Afonso Rabelo , Lima Rafael Rodrigues 
Published: November 2021

AbstractDifferent studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters associated to fluoride exposure are, in fact, still controversial. In this way, this systematic review and meta-analysis aimed to show if there is an association between fluoride exposure from different sources, doses and neurological disorders. Terms related to “Humans”; “Central nervous system”; “Fluorides”; and “Neurologic manifestations” were searched in a systematic way onPubMed,Scopus,Web of Science,Lilacs,CochraneandGoogle Scholar.All studies performed on humans exposed to fluoride were included on the final assessment. A meta-analysis was then performed and the quality level of evidence was performed using theGRADEapproach. Our search retrieved 4,024 studies, among which 27 fulfilled the eligibility criteria. The main source of fluoride was naturally fluoridated water. Twenty-six studies showed alterations related to Intelligence Quotient (IQ) while only one has evaluated headache, insomnia, lethargy, polydipsia and polyuria. Ten studies were included on the meta-analysis, which showed IQ impairment only for individuals under high fluoride exposure considering the World Health Organization criteria, without evidences of association between low levels and any neurological disorder. However, the high heterogeneity observed compromise the final conclusions obtained by the quantitative analyses regarding such high levels. Furthermore, this association was classified as very low-level evidence. At this time, the current evidence does not allow us to state that fluoride is associated with neurological damage, indicating the need for new epidemiological studies that could provide further evidences regarding this possible association.
Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
Authors: Brady Molly , McQuaid Conor , Solorzano Alexander , Johnson Angelique , Combs Abigail , Venkatraman Chethana , Rahman Akib , Leyva Hannah , Kwok Wing-Chi Edmund , Wood Ronald W. , Deane Rashid 
Published: November 2021

AbstractWhile there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it’s unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it’s unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes.
Quaternary landscape dynamics boosted species dispersal across Southeast Asia
Authors: Salles Tristan , Mallard Claire , Husson Laurent , Zahirovic Sabin , Sarr Anta-Clarisse , Sepulchre Pierre 
Published: November 2021

AbstractSundaland, the inundated shelf separating Java, Sumatra and Borneo from the Malay Peninsula, is of exceptional interest to biogeographers for its species richness and its position at the junction between the Australasian and Indomalay biogeographic provinces. Owing to its low elevation and relief, its physiography is contingent on relative sea-level change, which drove Quaternary species burst in response to flooding episodes. New findings show that the region was predominantly terrestrial during the Late Pleistocene requiring a reassessment of the drivers of its recent biodiversity history. Here we show that physiographic changes have modified the regional connectivity network and remodelled the pathways of species dispersal. From combined landscape evolution and connectivity models, we found four phases of drainage reorganisation and river captures. These changes have fragmented the environment into multiple habitats connected by migratory corridors that cover 8% of the exposed shelf and stretch across the biogeographic provinces. Our results support the theory that rapidly evolving physiography could foster Quaternary biodiversification across Southeast Asia.