bluuebunny/crossref_metadata_2025 huggingface dataset:
SCN9A variant in a family of mixed breed dogs with congenital insensitivity to pain
Authors: Gutierrez‐Quintana Rodrigo , Christen Matthias , Faller Kiterie M. E. , Guevar Julien , Jagannathan Vidhya , Leeb Tosso
Published: January 2023

Background

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSANs) are a rare group of genetic disorders causing inability to feel pain. Three different associated variants have been identified in dogs: 1 in Border Collies, 1 in mixed breed dogs, and 1 in Spaniels and Pointers.

Objectives

To clinically and genetically characterize CIP in a family of mixed breed dogs.

Animals

Two mixed breed dogs from the same litter were independently presented: 1 for evaluation of painless fractures, and the other for chronic thermal skin injuries.

Methods

Physical, neurological, and histopathological evaluations were performed. Whole genome sequencing of 1 affected dog was used to identify homozygous protein‐changing variants that were not present in 926 control genomes from diverse dog breeds.

Results

Physical and neurological examinations showed the absence of superficial and deep pain perception in the entire body. Histopathological evaluations of the brain, spinal cord and sensory ganglia were normal. Whole genome sequencing identified a homozygous missense variant in SCN9A, XM_038584713.1:c.2761C>T or XP_038440641.1:(p.Arg921Cys). Both affected dogs were homozygous for the mutant allele, which was not detected in 926 dogs of different breeds.

Conclusions and Clinical Importance

We confirmed the diagnosis of CIP in a family of mixed breed dogs and identified a likely pathogenic variant in the SCN9A gene. The clinical signs observed in these dogs mimic those reported in humans with pathogenic SCN9A variants causing CIP. This report is the first of a spontaneous pathogenic SCN9A variant in domestic animals.
Elongation factor 1 is a component of the Arabidopsis RNA polymerase II elongation complex and associates with a subset of transcribed genes
Authors: Markusch Hanna , Michl‐Holzinger Philipp , Obermeyer Simon , Thorbecke Claudia , Bruckmann Astrid , Babl Sabrina , Längst Gernot , Osakabe Akihisa , Berger Frédéric , Grasser Klaus D.
Published: January 2023

Elongation factors modulate the efficiency of mRNA synthesis by RNA polymerase II (RNAPII) in the context of chromatin, thus contributing to implement proper gene expression programmes. The zinc‐finger protein elongation factor 1 (ELF1) is a conserved transcript elongation factor (TEF), whose molecular function so far has not been studied in plants.

Using biochemical approaches, we examined the interaction of Arabidopsis ELF1 with DNA and histones in vitro and with the RNAPII elongation complex in vivo. In addition, cytological assays demonstrated the nuclear localisation of the protein, and by means of double‐mutant analyses, interplay with genes encoding other elongation factors was explored. The genome‐wide distribution of ELF1 was addressed by chromatin immunoprecipitation.

ELF1 isolated from Arabidopsis cells robustly copurified with RNAPII and various other elongation factors including SPT4‐SPT5, SPT6, IWS1, FACT and PAF1C. Analysis of a CRISPR‐Cas9‐mediated gene editing mutant of ELF1 revealed distinct genetic interactions with mutants deficient in other elongation factors. Moreover, ELF1 associated with genomic regions actively transcribed by RNAPII. However, ELF1 occupied only c. 33% of the RNAPII transcribed loci with preference for inducible rather than constitutively expressed genes.

Collectively, these results establish that Arabidopsis ELF1 shares several characteristic attributes with RNAPII TEFs.
Care Data Infrastructure: A U.S. Case Study
Authors: Folbre Nancy
Published: January 2023

This essay emphasizes the need to critically evaluate sources of survey data available to assess interactions between paid and unpaid care provision, including the extent of substitutability between unpaid work time and money expenditures. While it focuses on the U.S., it provides a framework for analysis of data infrastructure in other countries that could facilitate international comparisons and policy analysis.
Treatment of Class II malocclusion with anterior open bite and posterior crossbite with the aid of mini‐implants in a patient with Down syndrome: Clinical case report
Authors: Pithon Matheus Melo , Tanaka Orlando Motohiro
Published: January 2023

Objective

We report the orthodontic treatment of a class II malocclusion with anterior open bite and posterior crossbite in a patient with Down syndrome (DS) treated with mini‐implants.

Methods

Treatment began with rapid maxillary expansion with a Haas appliance, followed by dental alignment and leveling with a fixed appliance and the correction of class II dental relationships with the use of orthodontic mini‐implants associated with a sliding jig.

Results

The results obtained at the end of the treatment were satisfactory, with improvements in occlusion, including bite closure; maxillary expansion; and the correction of dental relationships.

Conclusion

When well‐planned, orthodontic treatment in a patient with DS achieves satisfactory results from a skeletal, occlusal, and facial perspective.
Landscapes of Liberation
Authors: Oehri Noah
Published: January 2023

Catholic mission from the mid-20th century onwards was complicated by geopolitical upheaval, church reform, and the emergent critique of the colonial power matrix to which the Church belonged. Missionary movements to Latin America coincided with visions for a progressive, radically transformative church. Landscapes of Liberation expands scholarship into liberation theology’s reception in Andean America and critically examines the interplay of the Catholic Church as a global institution with parishes as local actors. Through source material from both sides of the Atlantic, this book charts how a transnational network of pastoral agents and laypeople in Peru’s southern highlands claimed mission and development as intertwined tenets of spiritual and social life throughout three decades of agrarian reform, activism, and social conflict. Ultimately, this book reveals how transformative theories for rural development yield contingent transformations: concrete change, yet contested liberation.
Investigation of Roller Bearing Cage Pocket Lubrication and Friction
Authors: Peterson Wyatt , Sadeghi Farshid , Meinel Andreas , Grillenberger Hannes
Published: January 2023

A test rig was designed and developed to assess the lubrication and friction of a single cylindrical roller and a conformal cage pocket. The roller was lubricated via oil bath in a sealed housing. Inner and outer bearing raceway pieces were fixed above and below the roller to mimic the internal geometry of an actual bearing. The cage pocket was made from transparent acrylic to look inside the cage and observe oil flow during operation. A six-axis load cell was used to measure the torque generated by the entire test rig with and without the cage pocket and used to isolate the friction of the cage pocket. Experiments were conducted to investigate the effects of roller–pocket clearance, roller–raceway clearance, and roller oil submersion level at rest. Results suggest that roller bearing cage pocket friction increases with decreasing pocket clearance, increasing oil availability, and increasing operating speed. The oil was observed to coalesce into stable striations inside the cage pocket for many operating conditions. Striation width was observed to decrease with increasing speed, increasing pocket clearance, and decreasing oil availability. The striations were summarized by oil volume fraction inside the cage pocket, which decreased with increasing speed, decreasing pocket clearance, and decreasing oil availability. The current results provide new information about oil behavior inside roller bearing cage pockets during operation, and an approach is presented to estimate roller bearing cage pocket friction.
Characterizing In-Situ Metatarsal Fracture Risk During Simulated Workplace Impact Loading
Authors: Kalra Mayank , McGregor Martine E. , McLachlin Stewart D. , Cronin Duane S. , Chandrashekar Naveen
Published: January 2023

Metatarsal fractures represent the most common traumatic foot injury; however, metatarsal fracture thresholds remain poorly characterized, which affects performance targets for protective footwear. This experimental study investigated impact energies, forces, and deformations to characterize metatarsal fracture risk for simulated in situ workplace impact loading. A drop tower setup conforming to ASTM specifications for testing impact resistance of metatarsal protective footwear applied a target impact load (22–55 J) to 10 cadaveric feet. Prior to impact, each foot was axially loaded through the tibia with a specimen-specific bodyweight load to replicate a natural weight-bearing stance. Successive iterations of impact tests were performed until a fracture was observed with X-ray imaging. Descriptive statistics were computed for force, deformation, and impact energy. Correlational analysis was conducted on donor age, BMI, deformation, force, and impact energy. A survival analysis was used to generate injury risk curves (IRC) using impact energy and force. All 10 specimens fractured with the second metatarsal being the most common fracture location. The mean peak energy, force, and deformation during fracture were 46.6 J, 4640 N, 28.9 mm, respectively. Survival analyses revealed a 50% fracture probability was associated with 35.8 J and 3562 N of impact. Foot deformation was not significantly correlated (p = 0.47) with impact force, thus deformation is not recommended to predict metatarsal fracture risk. The results from this study can be used to improve test standards for metatarsal protection, provide performance targets for protective footwear developers, and demonstrate a methodological framework for future metatarsal fracture research.
Design Considerations for the Attenuation of Translational and Rotational Accelerations in American Football Helmets
Authors: McIver Kevin G. , Lee Patrick , Bucherl Sean , Talavage Thomas M. , Myer Gregory D. , Nauman Eric A.
Published: January 2023

Participants in American football experience repetitive head impacts that induce negative changes in neurocognitive function over the course of a single season. This study aimed to quantify the transfer function connecting the force input to the measured output acceleration of the helmet system to provide a comparison of the impact attenuation of various modern American football helmets. Impact mitigation varied considerably between helmet models and with location for each helmet model. The current data indicate that helmet mass is a key variable driving force attenuation, however flexible helmet shells, helmet shell cutouts, and more compliant padding can improve energy absorption.
Understanding Frugal Engineering for Equity: Exploring Convergence of Biological Designs and Social Innovations
Authors: Malshe Ajay P. , Bapat Salil , Fischer Lukas
Published: January 2023

Multiple global trends and drivers have resulted in a steep escalation of tech-socio-economic inequities in basic human needs across industrialized as well as industrializing nations. This escalation is paralleled by the growing trend of novel and simple frugal innovations for meeting basic human needs, which are applied across various communities in the world towards bridging gaps of inequity. Frugality in this context is defined as minimizing the use of capital resources while delivering effective manufacturing product outcomes. It is noteworthy that frugal innovations are abundantly observed in the biological designs in nature. This paper is aimed at understanding the methodology of frugal engineering behind the resulting frugal manufacturing innovations through discovering the cross-section of frameworks of biological designs in nature and equitable social innovations. Authors have applied the framework of biological designs as these designs are observed to deliver multifunctionality, resilience, and sustainability, which are key to a frugal and equitable innovation platform and achieved by the frugal engineering process. As water is one of the most basic human needs, this paper uses water as an illustrative example to understand the frugal engineering process. The authors discuss designs in nature from cactus, tree roots, and human skin, and design parallels in related frugal innovations namely in fog-capturing nets, ice stupa, and Zeer (pot-in-a-pot), respectively, for equitable water access. The authors propose and discuss a resulting methodology for frugal engineering. This methodology can be utilized as a starting point for developing case-specific socially conscious manufacturing solutions.
Design and Development of the Transmission for a Fully Actuated 5-Degrees-of-Freedom Compliant Robot Manipulator With a Single Motor
Authors: Pisetskiy Sergey , Kermani Mehrdad R.
Published: January 2023

This article presents a novel architecture for the actuation and transmission system of a 5-degrees-of-freedom (DOFs) compliant robot manipulator. The compliant behavior of the robot is achieved using inherently compliant magneto-rheological (MR) clutches introduced in antagonistic pairs in every joint of the manipulator. All five antagonistic MR clutch pairs are driven using a single brushless DC motor located in the base of the robot. The MR clutch pairs are coupled to the motor through a system of shafts, belts, and gears. Several possible architectures for realizing a suitable drive train are presented, and the advantages and disadvantages of each concept are analyzed. The most efficient architecture for the drive train is selected to complete the design of the manipulator. The kinematics of the manipulator using the adopted architecture is further analyzed, and the workspace of the system is presented. To the best of our knowledge, this is the first 5-DOF, fully actuated, compliant robotic manipulator that uses a single DC motor to achieve five independent axes of rotations.
Computational Fluid Dynamics Study on Exhaust Heat Recovery of Various Spiral Tube Heat Exchangers
Authors: Guo Pengyan , Cheng Wen , Chong Perk Lin , Xia Bin , Yang Aolei , Zeng Xinhao
Published: January 2023

With the continuous development of internal combustion engine technology, the thermal efficiency of traditional energy vehicles has been difficult to improve, and the heat loss caused by high-temperature exhaust emissions is an important reason for the low thermal efficiency. To utilize the exhaust heat, the aim is to develop various spiral tube heat exchanger designs, namely, constant curvature heat exchanger with baffle and variable curvature heat exchanger. The design has been evaluated by referring to the performance evaluation coefficient (PEC); furthermore, the convection coefficient h has been taken into consideration as well. The idea is to perform numerical studies via computational fluid dynamics package and evaluate the performance of the spiral tube heat exchanger designs. PEC is the relationship between the heat exchange intensity of the heat exchanger and the flow resistance of the working fluid. The results show that the PEC evaluation index of the heat exchanger is the best when the spiral diameter of the heat exchange tube is 120 mm, and with the increase of the tube diameter and pitch, the overall performance of the heat exchanger decreases. The research on heat transfer enhancement of heat exchangers was carried out, and various spiral tube heat exchangers were designed based on the structure of spiral heat exchange tubes. The variable curvature heat exchanger has better overall performance than the baffle constant curvature heat exchanger. Compared to the single-variable curvature and the double-variable curvature, the maximum PEC difference of them does not exceed 0.01, and the double-variable curvature is more sufficient in volume utilization, and it can save about 13% volume. Considering the use requirements of the actual vehicle waste heat recovery system, the double-variable curvature spiral tube heat exchanger is more suitable for practical engineering applications than the single-variable curvature spiral tube heat exchanger.
Multiple sources of acoustic variation affect speech processing efficiency
Authors: Kapadia Alexandra M. , Tin Jessica A. A. , Perrachione Tyler K.
Published: January 2023

Phonetic variability across talkers imposes additional processing costs during speech perception, evident in performance decrements when listening to speech from multiple talkers. However, within-talker phonetic variation is a less well-understood source of variability in speech, and it is unknown how processing costs from within-talker variation compare to those from between-talker variation. Here, listeners performed a speeded word identification task in which three dimensions of variability were factorially manipulated: between-talker variability (single vs multiple talkers), within-talker variability (single vs multiple acoustically distinct recordings per word), and word-choice variability (two- vs six-word choices). All three sources of variability led to reduced speech processing efficiency. Between-talker variability affected both word-identification accuracy and response time, but within-talker variability affected only response time. Furthermore, between-talker variability, but not within-talker variability, had a greater impact when the target phonological contrasts were more similar. Together, these results suggest that natural between- and within-talker variability reflect two distinct magnitudes of common acoustic–phonetic variability: Both affect speech processing efficiency, but they appear to have qualitatively and quantitatively unique effects due to differences in their potential to obscure acoustic–phonemic correspondences across utterances.
DNA dioxygenases Tet2/3 regulate gene promoter accessibility and chromatin topology in lineage-specific loci to control epithelial differentiation
Authors: Chen Guo-Dong , Fatima Iqra , Xu Qin , Rozhkova Elena , Fessing Michael Y. , Mardaryev Andrei N. , Sharov Andrey A. , Xu Guo-Liang , Botchkarev Vladimir A.
Published: January 2023

Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes, catalyzing 5-methylcytosine oxidation in DNA. Here, by using
Keratin 14
–
Cre
–driven ablation of
Tet
genes in skin epithelial cells, we demonstrate that ablation of
Tet2/Tet3
results in marked alterations of hair shape and length followed by hair loss. We show that, through DNA demethylation,
Tet2/Tet3
control chromatin accessibility and Dlx3 binding and promoter activity of the
Krt25
and
Krt28
genes regulating hair shape, as well as regulate interactions between the
Krt28
gene promoter and distal enhancer. Moreover,
Tet2/Tet3
also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation–independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control.
Syntaxin 1 Ser
14
phosphorylation is required for nonvesicular dopamine release
Authors: Shekar Aparna , Mabry Samuel J. , Cheng Mary H. , Aguilar Jenny I. , Patel Shalin , Zanella Daniele , Saleeby David P. , Zhu Yanqi , Romanazzi Tiziana , Ulery-Reynolds Paula , Bahar Ivet , Carter Angela M. , Matthies Heinrich J. G. , Galli Aurelio
Published: January 2023

Amphetamine (AMPH) is a psychostimulant that is commonly abused. The stimulant properties of AMPH are associated with its ability to increase dopamine (DA) neurotransmission. This increase is promoted by nonvesicular DA release mediated by reversal of DA transporter (DAT) function. Syntaxin 1 (Stx1) is a SNARE protein that is phosphorylated at Ser
14
by casein kinase II. We show that Stx1 phosphorylation is critical for AMPH-induced nonvesicular DA release and, in
Drosophila melanogaster
, regulates the expression of AMPH-induced preference and sexual motivation. Our molecular dynamics simulations of the DAT/Stx1 complex demonstrate that phosphorylation of these proteins is pivotal for DAT to dwell in a DA releasing state. This state is characterized by the breakdown of two key salt bridges within the DAT intracellular gate, causing the opening and hydration of the DAT intracellular vestibule, allowing DA to bind from the cytosol, a mechanism that we hypothesize underlies nonvesicular DA release.
Identification of AXL as a co-receptor for human parvovirus B19 infection of human erythroid progenitors
Authors: Ning Kang , Zou Wei , Xu Peng , Cheng Fang , Zhang Elizabeth Yan , Zhang-Chen Aaron , Kleiboeker Steve , Qiu Jianming
Published: January 2023

Parvovirus B19 (B19V) infects human erythroid progenitor cells (EPCs) and causes several hematological disorders and fetal hydrops. Amino acid (aa) 5–68 of minor capsid protein VP1 (VP1u
5–68aa
) is the minimal receptor binding domain for B19V to enter EPCs. Here, we carried out a genome-wide CRISPR-Cas9 guide RNA screen and identified tyrosine protein kinase receptor UFO (AXL) as a proteinaceous receptor for B19V infection of EPCs.
AXL
gene silencing in ex vivo expanded EPCs remarkably decreased B19V internalization and replication. Additions of the recombinant AXL extracellular domain or a polyclonal antibody against it upon infection efficiently inhibited B19V infection of ex vivo expanded EPCs. Moreover, B19V VP1u interacted with the recombinant AXL extracellular domain in vitro at a relatively high affinity (
K
D
 = 103 nM). Collectively, we provide evidence that AXL is a co-receptor for B19V infection of EPCs.
Targeting Src reactivates pyroptosis to reverse chemoresistance in lung and pancreatic cancer models
Authors: Su Liangping , Chen Yitian , Huang Cheng , Wu Sangqing , Wang XiaoJuan , Zhao Xinbao , Xu Qiuping , Sun Ruipu , Kong Xiangzhan , Jiang Xue , Qiu Xiaoyi , Huang Xiaoming , Wang Minghui , Wong Ping-Pui
Published: January 2023

Pancreatic and lung cancers frequently develop resistance to chemotherapy-induced cell apoptosis during the treatment, indicating that targeting nonapoptotic-related pathways, such as pyroptosis, can be an alternative cancer treatment strategy. Pyroptosis is a gasdermin-driven lytic programmed cell death triggered by inflammatory caspases when initiated by canonical or noncanonical pathways that has been recently seen as a potential therapeutic target in cancer treatment. However, overcoming chemoresistance in cancers by modulating pyroptosis has not been explored. Here, we demonstrate that β5-integrin represses chemotherapy-induced canonical pyroptosis to confer cancer chemoresistance through ASAH2-driven sphingolipid metabolic reprogramming. Clinically, high β5-integrin expression associates with poor patient prognosis and chemotherapeutic responses in cancers. In addition, chemoresistant cells in vitro fail to undergo chemotherapy-induced pyroptosis, which is controlled by β5-integrin. Mechanistically, proteomic and lipidomic analyses indicate that β5-integrin up-regulates sphingolipid metabolic enzyme ceramidase (ASAH2) expression through Src–signal transducer and activator of transcription 3 (STAT3) signaling, which then reduces the metabolite ceramide concentration and subsequent ROS production to prohibit chemotherapy-induced canonical pyroptosis. Using cancer cell lines, patient-derived tumor organoids, and orthotopic lung and pancreatic animal models, we show that administration of a Src or ceramidase inhibitor rescues the response of chemoresistant pancreatic and lung cancer cells to chemotherapy by reactivating pyroptosis in vitro and in vivo. Overall, our results suggest that pyroptosis-based therapy is a means to improve cancer treatment and warrants further investigation.
Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer
Authors: Budhraja Karan K. , McDonald Bradon R. , Stephens Michelle D. , Contente-Cuomo Tania , Markus Havell , Farooq Maria , Favaro Patricia F. , Connor Sydney , Byron Sara A. , Egan Jan B. , Ernst Brenda , McDaniel Timothy K. , Sekulic Aleksandar , Tran Nhan L. , Prados Michael D. , Borad Mitesh J. , Berens Michael E. , Pockaj Barbara A. , LoRusso Patricia M. , Bryce Alan , Trent Jeffrey M. , Murtaza Muhammed
Published: January 2023

Genome-wide fragmentation patterns in cell-free DNA (cfDNA) in plasma are strongly influenced by cellular origin due to variation in chromatin accessibility across cell types. Such differences between healthy and cancer cells provide the opportunity for development of novel cancer diagnostics. Here, we investigated whether analysis of cfDNA fragment end positions and their surrounding DNA sequences reveals the presence of tumor-derived DNA in blood. We performed genome-wide analysis of cfDNA from 521 samples and analyzed sequencing data from an additional 2147 samples, including healthy individuals and patients with 11 different cancer types. We developed a metric based on genome-wide differences in fragment positioning, weighted by fragment length and GC content [information-weighted fraction of aberrant fragments (iwFAF)]. We observed that iwFAF strongly correlated with tumor fraction, was higher for DNA fragments carrying somatic mutations, and was higher within genomic regions affected by copy number amplifications. We also calculated sample-level means of nucleotide frequencies observed at genomic positions spanning fragment ends. Using a combination of iwFAF and nine nucleotide frequencies from three positions surrounding fragment ends, we developed a machine learning model to differentiate healthy individuals from patients with cancer. We observed an area under the receiver operative characteristic curve (AUC) of 0.91 for detection of cancer at any stage and an AUC of 0.87 for detection of stage I cancer. Our findings remained robust with as few as 1 million fragments analyzed per sample, demonstrating that analysis of fragment ends can become a cost-effective and accessible approach for cancer detection and monitoring.
Blocking common γ chain cytokine signaling ameliorates T cell–mediated pathogenesis in disease models
Authors: Le Floc’h Audrey , Nagashima Kirsten , Birchard Dylan , Scott George , Ben Li-Hong , Ajithdoss Dharani , Gayvert Kaitlyn , Romero Hernandez Annabel , Herbin Olivier , Tay Amanda , Farrales Pamela , Korgaonkar Chandrashekhar K. , Pan Hao , Shah Sweta , Kamat Vishal , Chatterjee Ishita , Popke Jon , Oyejide Adelekan , Lim Wei Keat , Kim Jee H. , Huang Tammy , Franklin Matthew , Olson William , Norton Thomas , Perlee Lorah , Yancopoulos George D. , Murphy Andrew J. , Sleeman Matthew A. , Orengo Jamie M.
Published: January 2023

The common γ chain (γc; IL-2RG) is a subunit of the interleukin (IL) receptors for the γc cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The lack of appropriate neutralizing antibodies recognizing IL-2RG has made it difficult to thoroughly interrogate the role of γc cytokines in inflammatory and autoimmune disease settings. Here, we generated a γc cytokine receptor antibody, REGN7257, to determine whether γc cytokines might be targeted for T cell–mediated disease prevention and treatment. Biochemical, structural, and in vitro analysis showed that REGN7257 binds with high affinity to IL-2RG and potently blocks signaling of all γc cytokines. In nonhuman primates, REGN7257 efficiently suppressed T cells without affecting granulocytes, platelets, or red blood cells. Using REGN7257, we showed that γc cytokines drive T cell–mediated disease in mouse models of graft-versus-host disease (GVHD) and multiple sclerosis by affecting multiple aspects of the pathogenic response. We found that our xenogeneic GVHD mouse model recapitulates hallmarks of acute and chronic GVHD, with T cell expansion/infiltration into tissues and liver fibrosis, as well as hallmarks of immune aplastic anemia, with bone marrow aplasia and peripheral cytopenia. Our findings indicate that γc cytokines contribute to GVHD and aplastic anemia pathology by promoting these characteristic features. By demonstrating that broad inhibition of γc cytokine signaling with REGN7257 protects from immune-mediated disorders, our data provide evidence of γc cytokines as key drivers of pathogenic T cell responses, offering a potential strategy for the management of T cell–mediated diseases.
Understanding respiratory microbiome–immune system interactions in health and disease
Authors: Di Simone Sara K. , Rudloff Ina , Nold-Petry Claudia A. , Forster Samuel C. , Nold Marcel F.
Published: January 2023

Interactions between the developing microbiome and maturing immune system in early life are critical for establishment of a homeostasis beneficial to both host and commensals. The lung harbors a diverse community of microbes associated with health and local or systemic disease. We discuss how early life colonization and community changes correlate with immune development and health and disease throughout infancy, childhood, and adult life. We highlight key advances in microbiology, immunology, and computational biology that allow investigation of the functional relevance of interactions between the respiratory microbiome and host immune system, which may unlock the potential for microbiome-based therapeutics.
Differential Requirement for IRGM Proteins during Tuberculosis Infection in Mice
Authors: Wilburn Kaley M. , Meade Rachel K. , Heckenberg Emma M. , Dockterman Jacob , Coers Jörn , Sassetti Christopher M. , Olive Andrew J. , Smith Clare M.
Published: January 2023

Mycobacterium tuberculosis
(
Mtb
) is a bacterium that exclusively resides in human hosts and remains a dominant cause of morbidity and mortality among infectious diseases worldwide. Host protection against
Mtb
infection is dependent on the function of immunity-related GTPase clade M (IRGM) proteins.
The Early Microbial Colonizers of a Short-Lived Volcanic Island in the Kingdom of Tonga
Authors: Dragone Nicholas B. , Whittaker Kerry , Lord Olivia M. , Burke Emily A. , Dufel Helen , Hite Emily , Miller Farley , Page Gabrielle , Slayback Dan , Fierer Noah
Published: January 2023

The volcanic island of Hunga Tonga Hunga Ha’apai in the Kingdom of Tonga represents a very rare example of new island formation and thus a unique opportunity to study how organisms colonize a new landmass. We found that the island was colonized by diverse microbial communities shortly after its formation in 2015, with these microbes likely originating from nearby geothermal environments.
Seasonal Shifts in Bacterial and Fungal Microbiomes of Leaves and Associated Leaf-Mining Larvae Reveal Persistence of Core Taxa Regardless of Diet
Authors: Šigutová Hana , Šigut Martin , Pyszko Petr , Kostovčík Martin , Kolařík Miroslav , Drozd Pavel
Published: January 2023

Leaf miners are endophagous insect herbivores that feed on plant tissues and develop and live enclosed between the epidermis layers of a single leaf for their entire life cycle. Such close association is a precondition for the evolution of more intimate host-microbe relationships than those found in free-feeding herbivores.
Rapid Assessment of SARS-CoV-2 Variant-Associated Mutations in Wastewater Using Real-Time RT-PCR
Authors: Farkas Kata , Pellett Cameron , Williams Rachel , Alex-Sanders Natasha , Bassano Irene , Brown Mathew R. , Denise Hubert , Grimsley Jasmine M. S. , Kevill Jessica L. , Khalifa Mohammad S. , Pântea Igor , Story Rich , Wade Matthew J. , Woodhall Nick , Jones Davey L.
Published: January 2023

With the global spread of COVID-19, it is essential to identify emerging variants which may be more harmful or able to escape vaccines rapidly. To date, the gold standard to assess variants circulating in communities has been the sequencing of the S gene or the whole genome of SARS-CoV-2; however, that approach is time-consuming and expensive.
Rapid Identification of Pseudomonas aeruginosa International High-Risk Clones Based on High-Resolution Melting Analysis
Authors: Dufkova Kristyna , Bezdicek Matej , Nykrynova Marketa , Kocmanova Iva , Kubackova Petra , Hanslikova Jana , Fejkova Karolina , Mayer Jiri , Lengerova Martina
Published: January 2023

In this study, we designed a novel mini-MLST typing scheme for
Pseudomonas aeruginosa
. Its great discriminatory power, together with ease of performance and short processing time, makes this approach attractive for prospective typing of large isolate sets. Integrating the novel
P. aeruginosa
molecular typing scheme enables the development and spread of MDR/XDR high-risk clones to be investigated.
Provenance of eolian deposits in the Xorkol Basin: Implications for Eocene dust-transport pattern in western China
Authors: Pan Feng , Li Jianxing , Nie Junsheng , Xu Yong , Yue Leping
Published: January 2023

Atmospheric circulation in western China significantly affects the inland climate of Asia. Constraining the provenance of eolian sequences can provide robust evidence for dust-transport pathways, and thus the evolution of paleo-atmospheric circulation. Western China has been dominated by the westerly wind regime since the late Oligocene, as demonstrated by provenance studies of eolian deposits. However, the wind regime responsible for the accumulation of eolian deposits during the Eocene is unclear due to a lack of corresponding provenance studies. Here, we present the first provenance analysis for an Eocene (ca. 51−40 Ma) eolian Red Clay sequence in the Xishuigou Formation of the Xorkol Basin in western China, based on multiproxy geochemical and geochronological data. Comparison of zircon U−Pb ages from the Xishuigou sequence with ages from potential source regions reveals that the northern piedmont of the West Kunlun Range was a persistent source, although sediments from the nearby Altun-Xorkol region were an important dust source for the lower part of the Xishuigou sequence which were deposited between ca. 51 Ma and 46.5 Ma. These results reveal that the westerly dust-transport pattern has been dominant in western China since at least ca. 51 Ma. The similarity of provenance between the Eocene Red Clay of the Xishuigou Formation and the Neogene eolian sequence of the overlying Caihonggou Formation in the same area implies that this dust-transport pattern was stable from the Eocene to the Neogene, despite dramatic changes in paleogeography, paleotopography, and global climate.
Coagulopathy is an under-recognised complication of acquired HLH
Authors: Kosciejew Serena , Morris Edward , Wight Joel
Published: January 2023

Acquired haemophagocytic lymphohistiocytosis (aHLH) is a rare and often fatal process of uncontrolled cytokine release driven by the inability of natural killer cells to eliminate infected or malignant cells. Herein, we report two cases of aHLH complicated by bleeding secondary to coagulopathy due to hypofibrinogenaemia and thrombocytopenia despite appropriate correction with blood products. These cases highlight the effect coagulopathy and thrombocytopenia can have on patient outcomes when trying to confirm and manage the underlying process driving aHLH.
Mantle cell lymphoma presenting as intussuscepting ascending colon mass
Authors: Tan Lydia Li Yeh , Chang Heidi , Maduka Ishara
Published: January 2023

Malignant lymphoma is a rare cause of gastrointestinal intussusception in adults, accounting for less than 1% of all cases of intussusception. This is a case of a South-East Asian woman in her 50s, presenting with intermittent abdominal pain, loose stools and weight loss. CT of the abdomen and pelvis showed an irregular mass causing ileocolic intussusception and she underwent emergency open right hemicolectomy with end ileostomy. Intraoperatively, her bowel was covered with lymphoma nodules, and bulky mesenteric nodules of small bowel and colon were seen. The histology shows mantle cell lymphoma, a rare subtype of B cell non-Hodgkin’s lymphoma. She recovered well postoperatively and was started on chemotherapy (Nordic protocol) early.
Refractory coronary vasospasm and recurrent cardiac arrest
Authors: Birs Antoinette S , Darden Douglas , Adler Eric D , Feld Gregory K
Published: January 2023

We present a case of recurrent vasospasm as an uncommon cause of ventricular fibrillation in a young female patient who was found to have a genetic mutation of unknown significance in the desmoplakin (DSP) gene and ultimately required an implantable cardiac defibrillator and percutaneous coronary intervention. Refractory vasospasm as a cause of chest pain and cardiac arrest may be under-recognised. In this manuscript, we highlight the natural history of refractory vasospasm, treatment considerations including medical therapy, implantable cardiac defibrillator and percutaneous coronary intervention. Lastly, we explore the potential correlation between the DSP mutation and her clinical presentation and the growing importance of genetic testing in unexplained cardiac arrest.
S100A10 promotes HCC development and progression via transfer in extracellular vesicles and regulating their protein cargos
Authors: Wang Xia , Huang Hongyang , Sze Karen Man-Fong , Wang Jin , Tian Lu , Lu Jingyi , Tsui Yu-Man , Ma Hoi Tang , Lee Eva , Chen Ao , Lee Joyce , Wang Ying , Yam Judy Wai Ping , Cheung Tan-To , Guan Xinyuan , Ng Irene Oi-Lin
Published: January 2023

Objective

Growing evidence indicates that tumour cells exhibit characteristics similar to their lineage progenitor cells. We found that S100 calcium binding protein A10 (S100A10) exhibited an expression pattern similar to that of liver progenitor genes. However, the role of S100A10 in hepatocellular carcinoma (HCC) progression is unclear. Furthermore, extracellular vesicles (EVs) are critical mediators of tumourigenesis and metastasis, but the extracellular functions of S100A10, particularly those related to EVs (EV-S100A10), are unknown.

Design

The functions and mechanisms of S100A10 and EV-S100A10 in HCC progression were investigated in vitro and in vivo. Neutralising antibody (NA) to S100A10 was used to evaluate the significance of EV-S100A10.

Results

Functionally, S100A10 promoted HCC initiation, self-renewal, chemoresistance and metastasis in vitro and in vivo. Of significance, we found that S100A10 was secreted by HCC cells into EVs both in vitro and in the plasma of patients with HCC. S100A10-enriched EVs enhanced the stemness and metastatic ability of HCC cells, upregulated epidermal growth factor receptor (EGFR), AKT and ERK signalling, and promoted epithelial–mesenchymal transition. EV-S100A10 also functioned as a chemoattractant in HCC cell motility. Of significance, S100A10 governed the protein cargos in EVs and mediated the binding of MMP2, fibronectin and EGF to EV membranes through physical binding with integrin αⅤ. Importantly, blockage of EV-S100A10 with S100A10-NA significantly abrogated these enhancing effects.

Conclusion

Altogether, our results uncovered that S100A10 promotes HCC progression significantly via its transfer in EVs and regulating the protein cargoes of EVs. EV-S100A10 may be a potential therapeutic target and biomarker for HCC progression.
Evaluating anthropogenic influence on a mesopredator: opossum (Didelphis virginiana) isotope values influenced by corn agriculture more than urbanization
Authors: Walsh Lisa L. , Tucker Priscilla K.
Published: January 2023

The composition of North American communities is changing due to anthropogenic land-use alteration. Mammalian mesopredators’ ability to consume anthropogenic trash due to their generalist diet has been referenced to partially explain their success in altered landscapes as they spread northward. We evaluated this assumption using carbon isotope values (δ13C) of the Virginia opossum ( Didelphis virginiana (Kerr, 1792)), a mesopredator expanding its range. δ13C values increase from consumption of C4 plants, including corn, a common food additive in North America. Opossum hairs from the Midwestern U.S. and Northeast were evaluated using generalized linear mixed models (GLMMs) to compare the predictive performances between winter harshness variables and anthropogenic variables. We also evaluated δ13C values through time to test if the temporal pattern of increased corn additives is mirrored in northern opossums. The best-performing GLMM included year and percentage corn fields as positive covariates. Variance in δ13C values increased exclusively in the “cornbelt” Midwest after 1970. δ13C values compared across space and time bolster evidence for the influence of agricultural development on the opossum’s range expansion.
Asymptotic behavior for a commutative and noncommutative in coordinates Mixmaster model
Authors: Astorga-Moreno J. A. , Castellanos-Cervantes U. I. , Diaz-Gutierrez E. , Mena-Barboza E. A.
Published: January 2023

In this work, we find the asymptotic behavior for a commutative and noncommutative Mixmaster model in a Quantum Cosmology (QC) and semiclassical scenario, showing explicitly the calculus and applying the asymptotically equivalent functions that allow us to analyze the equivalence between Bianchi IX and Bianchi II models.
Prediction Quality Meta Regression and Error Meta Classification for Segmented Lidar Point Clouds
Authors: Colling Pascal , Rottmann Matthias , Roese-Koerner Lutz , Gottschalk Hanno
Published: January 2023

We present a post-processing tool for semantic segmentation of Lidar point clouds, called LidarMetaSeg, which estimates the prediction quality segmentwise and classifies prediction errors. For this purpose, we compute dispersion measures based on network probability outputs as well as feature measures based on point cloud input features and aggregate them on segment level. These aggregated measures are used to train a meta classification model to predict whether a predicted segment is an error, i.e., it is a false positive or not. We also train a meta regression model to predict the segmentwise prediction quality in terms of intersection over union. Both models can then be applied to semantic segmentation inferences without knowing the ground truth. In our experiments we use different Lidar segmentation models and datasets and analyze the power of our method. We show that our results outperform other standard approaches based on single uncertainty measures like entropy. Furthermore, we present an in-depth evaluation of our method on predicted classes as well as on predicted categories.
QHAN: Quantum-inspired Hierarchical Attention Mechanism Network for Question Answering
Authors: Guo Peng , Wang Panpan
Published: January 2023

The approach to question answering is challenging because it usually requires finding useful information from within and between question and answer sentences for sentence semantic matching. The key information mined from existing question and answer sentences, as a supplement to semantic information, maybe helpful for this task. However, capturing the intra-sentence and inter-sentence semantic interactions is somewhat difficult given the implicit interrelationships between question and answer sentences. Although the learning effect of multi-layer neural network is good, it lacks explanatory and theoretical support. This paper mainly studies how to select the best answer sentence from a set of question and answer sentences, mine information more effectively, perform semantic matching, and have a certain interpretability. Therefore, we propose a hierarchical attention network (QHAN) based on the mathematical framework of quantum theory, which integrates the attention mechanism under quantum measurement and density matrix (DMATT) and the attention mechanism under quantum weak measurement and weak value (WMATT) in one in a unified model framework. QHAN can not only discover key sentences in a set of question and answer sentences and key words in a sentence, but also perform sentence semantic matching quickly and accurately. Furthermore, QHAN has the advantage of interpretability in terms of models due to the physical meaning and attentional full weight distribution implied by quantum theory. Extensive experiments on the question answering dataset show that our method is comparable to the baselines and can explain why the selected question and answer sentence is the best option in terms of intra-sentence and inter-sentence attention distributions.
HX and Me: Understanding Allostery, Folding, and Protein Machines
Authors: Englander S. Walter
Published: January 2023

My accidental encounter with protein hydrogen exchange (HX) at its very beginning and its continued development through my scientific career have led us to a series of advances in HX measurement, interpretation, and cutting edge biophysical applications. After some thoughts about how life brought me there, I take the opportunity to reflect on our early studies of allosteric structure and energy change in hemoglobin, the still-current protein folding problem, and our most recent forward-looking studies on protein machines.
3D Thermal Simulation of Lithium-Ion Battery Thermal Runaway in Autoclave Calorimetry: Development and Comparison of Modeling Approaches
Authors: Hoelle S. , Dengler F. , Zimmermann S. , Hinrichsen O.
Published: January 2023

In this paper, three different empirical modeling approaches for the heat release during a battery cell thermal runaway (TR) are analyzed and compared with regard to their suitability for TR and TR propagation simulation. Therefore, the so called autoclave calorimetry experiment conducted with a prismatic lithium-ion battery (>60 Ah) is modeled within the 3D-CFD framework of Simcenter Star-CCM+® and the simulation results are compared to the experiments. In addition, the influence of critical parameters such as mass loss during TR, the jelly roll’s specific heat capacity and thermal conductivity is analyzed. All of the three modeling approaches are able to reproduce the experimental results with high accuracy, but there are significant differences regarding computational effort. Furthermore, it is crucial to consider that the mass loss during TR and both specific heat capacity as well as thermal conductivity of the jelly roll have a significant influence on the simulation results. The advantages and disadvantages of each modeling approach pointed out in this study and the identification of crucial modeling parameters contribute to the improvement of both TR as well as TR propagation simulation and help researchers or engineers to choose a suitable model to design a safer battery pack.
Imprinting Sensor Based on Honeycomb Graphene Oxide for the Determination of Echinacoside in Complex Samples
Authors: Ma Jing , Wang YanPing , Zhu Xiumei , Cui Fang , Li Yuanyuan , Zhang-Peng Xinru , Wang Zixia , Hu Fangdi , Shi Xiaofeng
Published: January 2023

Echinacoside(ECH) is a phenylethanoid glycoside compound with various pharmacological activity in Chinese medicine. The development of convenient, efficient and sensitive analysis methods for ECH in complex samples in vitro and in vivo has considerable application value. In this study, honeycomb graphene oxide (H-GO) with highly conductivity and nanoscale defect-like structure was successfully prepared by combustion method. It was used as a modified material for flexible electrode (ITO-PET), and then activated in alkaline solution to construct a nanomaterial modified electrode (aH-GO/ITO-PET). The imprinted sensor (MIP/aH-GO/ITO-PET) was further constructed by simple electropolymerization and elution. Under optimized conditions, the sensor achieves sensitive detection of ECH in a wide linear range of 0.1 ∼ 100 μM, with a detection limit as low as 1.6 nM (S/N = 3), and has good repeatability, stability and anti-interference. It has been successfully used for the direct detection of ECH in Cistanche deserticola Ma wine and rat plasma.