bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscopic approach to the description of spin torques in two-dimensional Rashba ferromagnets and antiferromagnets
Authors: Pervishko A A , Yudin D I
Published: April 2021

We review the most significant results obtained in the framework of the microscopic approach to a systematic study of magnetic dynamics in two-dimensional ferromagnetic and antiferromagnetic materials with a strong Rashba spin-orbit coupling. For model systems, we discuss the microscopic derivation of the Gilbert damping tensor, spin-orbit and spin-transfer torques, and symmetric and antisymmetric exchange interactions. It is shown that in both antiferromagnetic and ferromagnetic systems, the presence of a sufficiently strong spin-orbit coupling leads to an anisotropy of spin torques and Gilbert damping. We focus on an analysis of spin-orbit torques in a two-dimensional Rashba antiferromagnet. We also address the possibility of switching the antiferromagnetic order parameter via short current pulses in the plane of the sample.
Computerized dynamic fluid simulation (CFD) for measuring the influence of the cab deflector on the aerodynamics of trucks
Authors: Lazăr Sergiu
Published: April 2021

This paper refers to how the cab deflector of trucks can influence the aerodynamic
coefficient. The first part of the paper includes some generalities taken from previous studies, regarding the types of solutions to improve aerodynamics for trucks. The second part of the paper is a more practical one and has two main chapters: modeling and simulation of modeled parts. In this sense, a truck and 3 cabin deflectors were schematically modeled in Catia v5. After assembly in the Catia v5 program, the impact of the cabin deflector was analyzed. Thus, a computerized dynamic fluid simulation (CFD) was performed using the specific module in Ansys. The simulation included the CFD analysis of the four possible variants: truck without deflector, truck + deflector 1, truck + deflector 2, truck + deflector 3. All mentioned variants were analyzed at 3 different speeds: 50 km / h, 70 km / h and 90 km /. This analysis revealed information on the efficiency of each deflector, the value of the pressure as well as the most affected areas, the value of the turbulent kinetic energy, the value of the drag force and the aerodynamic coefficient.
Two-Phase Lineage Specification of Telencephalon Progenitors Generated From Mouse Embryonic Stem Cells
Authors: Nasu Makoto , Esumi Shigeyuki , Hatakeyama Jun , Tamamaki Nobuaki , Shimamura Kenji
Published: April 2021

Proper brain development requires precisely controlled phases of stem cell proliferation, lineage specification, differentiation, and migration. Lineage specification depends partly on concentration gradients of chemical cues called morphogens. However, the rostral brain (telencephalon) expands prominently during embryonic development, dynamically altering local morphogen concentrations, and telencephalic subregional properties develop with a time lag. Here, we investigated how progenitor specification occurs under these spatiotemporally changing conditions using a three-dimensionalin vitrodifferentiation model. We verified the critical contributions of three signaling factors for the lineage specification of subregional tissues in the telencephalon, ventralizing sonic hedgehog (Shh) and dorsalizing bone morphogenetic proteins (BMPs) and WNT proteins (WNTs). We observed that a short-lasting signal is sufficient to induce subregional progenitors and that the timing of signal exposure for efficient induction is specific to each lineage. Furthermore, early and late progenitors possess different Shh signal response capacities. This study reveals a novel developmental mechanism for telencephalon patterning that relies on the interplay of dose- and time-dependent signaling, including a time lag for specification and a temporal shift in cellular Shh sensitivity. This delayed fate choice through two-phase specification allows tissues with marked size expansion, such as the telencephalon, to compensate for the changing dynamics of morphogen signals.
The Role of PDE8 in T Cell Recruitment and Function in Inflammation
Authors: Epstein Paul M. , Basole Chaitali , Brocke Stefan
Published: April 2021

Inhibitors targeting cyclic nucleotide phosphodiesterases (PDEs) expressed in leukocytes have entered clinical practice to treat inflammatory disorders, with three PDE4 inhibitors currently in clinical use as therapeutics for psoriasis, psoriatic arthritis, atopic dermatitis and chronic obstructive pulmonary disease. In contrast, the PDE8 family that is upregulated in pro-inflammatory T cells is a largely unexplored therapeutic target. It was shown that PDE8A plays a major role in controlling T cell and breast cancer cell motility, including adhesion to endothelial cells under physiological shear stress and chemotaxis. This is a unique function of PDE8 not shared by PDE4, another cAMP specific PDE, employed, as noted, as an anti-inflammatory therapeutic. Additionally, a regulatory role was shown for the PDE8A-rapidly accelerated fibrosarcoma (Raf)-1 kinase signaling complex in myelin antigen reactive CD4+effector T cell adhesion and locomotion by a mechanism differing from that of PDE4. The PDE8A-Raf-1 kinase signaling complex affects T cell motility, at least in part, via regulating the LFA-1 integrin mediated adhesion to ICAM-1. The findings that PDE8A and its isoforms are expressed at higher levels in naive and myelin oligodendrocyte glycoprotein (MOG)35–55activated effector T (Teff) cells compared to regulatory T (Treg) cells and that PDE8 inhibition specifically affects MOG35–55activated Teff cell adhesion, indicates that PDE8A could represent a new beneficial target expressed in pathogenic Teff cells in CNS inflammation. The implications of this work for targeting PDE8 in inflammation will be discussed in this review.
Pathophysiological Significance of WDR62 and JNK Signaling in Human Diseases
Authors: Zhi Yiqiang , Zhou Xiaokun , Yu Jurui , Yuan Ling , Zhang Hongsheng , Ng Dominic C. H. , Xu Zhiheng , Xu Dan
Published: April 2021

The c-Jun N-terminal kinase (JNK) is highly evolutionarily conserved and plays important roles in a broad range of physiological and pathological processes. The WD40-repeat protein 62 (WDR62) is a scaffold protein that recruits different components of the JNK signaling pathway to regulate several human diseases including neurological disorders, infertility, and tumorigenesis. Recent studies revealed that WDR62 regulates the process of neural stem cell mitosis and germ cell meiosis through JNK signaling. In this review we summarize the roles of WDR62 and JNK signaling in neuronal and non-neuronal contexts and discuss how JNK-dependent signaling regulates both processes. WDR62 is involved in various human disorders via JNK signaling regulation, and may represent a promising therapeutic strategy for the treatment of related diseases.
Non-Canonical Wnt Signaling Regulates Cochlear Outgrowth and Planar Cell Polarity via Gsk3β Inhibition
Authors: Landin Malt Andre , Clancy Shaylyn , Hwang Diane , Liu Alice , Smith Connor , Smith Margaret , Hatley Maya , Clemens Christopher , Lu Xiaowei
Published: April 2021

During development, sensory hair cells (HCs) in the cochlea assemble a stereociliary hair bundle on their apical surface with planar polarized structure and orientation. We have recently identified a non-canonical, Wnt/G-protein/PI3K signaling pathway that promotes cochlear outgrowth and coordinates planar polarization of the HC apical cytoskeleton and alignment of HC orientation across the cochlear epithelium. Here, we determined the involvement of the kinase Gsk3β and the small GTPase Rac1 in non-canonical Wnt signaling and its regulation of the planar cell polarity (PCP) pathway in the cochlea. We provided the first in vivo evidence for Wnt regulation of Gsk3β activity via inhibitory Ser9 phosphorylation. Furthermore, we carried out genetic rescue experiments of cochlear defects caused by blocking Wnt secretion. We showed that cochlear outgrowth was partially rescued by genetic ablation of Gsk3β but not by expression of stabilized β-catenin; while PCP defects, including hair bundle polarity and junctional localization of the core PCP proteins Fzd6 and Dvl2, were partially rescued by either Gsk3β ablation or constitutive activation of Rac1. Our results identify Gsk3β and likely Rac1 as downstream components of non-canonical Wnt signaling and mediators of cochlear outgrowth, HC planar polarity, and localization of a subset of core PCP proteins in the cochlea.
Mitigation of Sodium Iodate-Induced Cytotoxicity in Retinal Pigment Epithelial Cells in vitro by Transgenic Erythropoietin-Expressing Mesenchymal Stem Cells
Authors: Koh Avin Ee-Hwan , Subbiah Suresh Kumar , Farhana Aisha , Alam Mohammad Khursheed , Mok Pooi Ling
Published: April 2021

Mesenchymal stem cells (MSC) have shown promise in restoring the vision of patients in clinical trials. However, this therapeutic effect is not observed in every treated patient and is possibly due to the inefficacies of cell delivery and high cell death following transplantation. Utilizing erythropoietin can significantly enhance the regenerative properties of MSCs and hence improve retinal neuron survivability in oxidative stress. Hence, this study aimed to investigate the efficacy of conditioned medium (CM) obtained from transgenic human erythropoietin-expressing MSCs (MSCEPO) in protecting human retinal pigment epithelial cells from sodium iodate (NaIO3)-induced cell death. Human MSC and MSCEPO were first cultured to obtain conditioned media (CM). The IC50 of NaIO3 in the ARPE-19 culture was then determined by an MTT assay. After that, the efficacy of both MSC-CM and MSC-CMEPO in ARPE-19 cell survival were compared at 24 and 48 h after NaIO3 treatment with MTT. The treatment effects on mitochondrial membrane potential was then measured by a JC-1 flow cytometric assay. The MTT results indicated a corresponding increase in cell survivability (5–58%) in the ARPE-19 cell cultures. In comparison to MSC-CM, the use of conditioned medium collected from the MSC-CMEPO further enhanced the rate of ARPE-19 survivability at 24 h (P < 0.05) and 48 h (P < 0.05) in the presence of NaIO3. Furthermore, more than 90% were found viable with the JC-1 assay after MSC-CMEPO treatment, showing a positive implication on the mitochondrial dynamics of ARPE-19. The MSC-CMEPO provided an enhanced mitigating effect against NaIO3-induced ARPE-19 cell death over that of MSC-CM alone during the early phase of the treatment, and it may act as a future therapy in treating retinal degenerative diseases.
USP44 Stabilizes DDB2 to Facilitate Nucleotide Excision Repair and Prevent Tumors
Authors: Zhang Ying , Mandemaker Imke K. , Matsumoto Syota , Foreman Oded , Holland Christopher P. , Lloyd Whitney R. , Sugasawa Kaoru , Vermeulen Wim , Marteijn Jurgen A. , Galardy Paul J.
Published: April 2021

Nucleotide excision repair (NER) is a pathway involved in the repair of a variety of potentially mutagenic lesions that distort the DNA double helix. The ubiquitin E3-ligase complex UV-DDB is required for the recognition and repair of UV-induced cyclobutane pyrimidine dimers (CPDs) lesions through NER. DDB2 directly binds CPDs and subsequently undergoes ubiquitination and proteasomal degradation. DDB2 must remain on damaged chromatin, however, for sufficient time to recruit and hand-off lesions to XPC, a factor essential in the assembly of downstream repair components. Here we show that the tumor suppressor USP44 directly deubiquitinates DDB2 to prevent its premature degradation and is selectively required for CPD repair. Cells lacking USP44 have impaired DDB2 accumulation on DNA lesions with subsequent defects in XPC retention. The physiological importance of this mechanism is evident in that mice lackingUsp44are prone to tumors induced by NER lesions introduced by DMBA or UV light. These data reveal the requirement for highly regulated ubiquitin addition and removal in the recognition and repair of helix-distorting DNA damage and identify another mechanism by which USP44 protects genomic integrity and prevents tumors.
5-Hydroxytryptamine, Glutamate, and ATP: Much More Than Neurotransmitters
Authors: Franco Rafael , Rivas-Santisteban Rafael , Lillo Jaume , Camps Jordi , Navarro Gemma , Reyes-Resina Irene
Published: April 2021

5-hydroxytryptamine (5-HT) is derived from the essential amino acid L-tryptophan. Although the compound has been studied extensively for its neuronal handling and synaptic actions, serotonin 5-HT receptors can be found extra-synaptically and not only in neurons but in many types of mammalian cells, inside and outside the central nervous system (CNS). In sharp contrast, glutamate (Glu) and ATP are better known as metabolism-related molecules, but they also are neurotransmitters, and their receptors are expressed on almost any type of cell inside and outside the nervous system. Whereas 5-hydroxytryptamine and Glu are key regulators of the immune system, ATP actions are more general. 5-hydroxytryptamine, ATP and Glu act through both G protein-coupled receptors (GPCRs), and ionotropic receptors, i.e., ligand gated ion channels. These are the three examples of neurotransmitters whose actions as holistic regulatory molecules are briefly put into perspective here.
Unraveling the Extracellular Metabolism of Immortalized Hippocampal Neurons Under Normal Growth Conditions
Authors: Campanella Beatrice , Colombaioni Laura , Nieri Riccardo , Benedetti Edoardo , Onor Massimo , Bramanti Emilia
Published: April 2021

Metabolomic profiling of cell lines has shown many potential applications and advantages compared to animal models and human subjects, and an accurate cellular metabolite analysis is critical to understanding both the intracellular and extracellular environments in cell culture. This study provides a fast protocol to investigatein vitrometabolites of immortalized hippocampal neurons HN9.10e with minimal perturbation of the cell system using a targeted approach. HN9.10e neurons represent a reliable model of one of the most vulnerable regions of the central nervous system. Here, the assessment of their extracellular metabolic profile was performed by studying the cell culture medium before and after cell growth under standard conditions. The targeted analysis was performed by a direct, easy, high-throughput reversed-phase liquid chromatography with diode array detector (RP-HPLC-DAD) method and by headspace solid-phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS) for the study of volatile organic compounds (VOCs). The analysis of six different batches of cells has allowed to investigate the metabolic reproducibility of neuronal cells and to describe the metabolic “starting” conditions that are mandatory for a well-grounded interpretation of the results of any following cellular treatment. An accurate study of the metabolic profile of the HN9.10e cell line has never been performed before, and it could represent a quality parameter before any other targeting assay or further exploration.
Using Cu–Zn–Sn–O Precursor to Optimize CZTSSe Thin Films Fabricated by Se Doping With CZTS Thin Films
Authors: Li Qian , Hu Jinpeng , Cui Yaru , Wang Juan , Hao Yu , Shen Tong , Duan Lizhen
Published: April 2021

The copper–zinc–tin oxide (CZTO) precursor was synthesized to avoid sudden volume expansion from CZTO precursor to Cu2ZnSnS4 (CZTS) thin films and smooth CZTSSe thin-film surfaces without pinholes. The CZTO precursor was prepared by coprecipitation and ball milling to form nanoink of CZTO. Based on the CZTO precursor, the CZTS thin film was fabricated and then selenized to make pinhole-free and flat Cu2ZnSn(S,Se)4(CZTSSe) thin films. The results show that the CZTO precursor greatly contributed to elevating the homologous surface characteristics and crystallinity of CZTSSe thin films by controlling selenium temperature, selenium time, and selenium source temperature. Finally, the conversion efficiency of the CZTSSe thin-film solar cell fabricated from the CZTO precursor was 4.11%, with an open-circuit voltage (Voc) of 623 mV, a short circuit current density (Jsc) of 16.02 mA cm−2, and a fill factor (FF) of 41.2%.
Lossen Rearrangement of p-Toluenesulfonates of N-Oxyimides in Basic Condition, Theoretical Study, and Molecular Docking
Authors: Kijewska Monika , Sharfalddin Abeer A. , Jaremko Łukasz , Cal Marta , Setner Bartosz , Siczek Miłosz , Stefanowicz Piotr , Hussien Mostafa A. , Emwas Abdul-Hamid , Jaremko Mariusz
Published: April 2021

The sulfonic esters of N-oxyimides are a group of compounds with a wide range of biological activities, as well as a unique reactivity toward amines. They undergo this reaction with primary amines and other nucleophilic reagents according to a Lossen-like rearrangement. The reaction is initiated by nucleophilic attack on a carbonyl group in the succinimide ring followed by isocyanate formation, which next interacts with another nucleophile molecule forming an addition product (e.g., ureido or urethane derivative). However, the secondary amines are also susceptible to other reactions leading to products containing the maleimide ring formed by sulphonic acid elimination. In the case of tertiary amines, this reaction is predominant. To explain the phenomenon of the reactivity of the N- oxyimides toward different types of amines, we employed various spectroscopic and X-ray approaches as well as DFT calculation. Results suggest that the basicity of the amine used for the reaction plays a crucial role in the reaction mechanism that eventually dominates the entire chemical process. Moreover, we applied molecular docking to investigate the ability of the products to act as serine protease inhibitors using human leukocyte elastase (HLE).
Gut Microbiota and Diarrhea: An Updated Review
Authors: Li Yunxia , Xia Siting , Jiang Xiaohan , Feng Can , Gong Saiming , Ma Jie , Fang Zhengfeng , Yin Jie , Yin Yulong
Published: April 2021

Diarrhea is a common problem to the whole world and the occurrence of diarrhea is highly associated with gut microbiota, such as bacteria, fungi, and viruses. Generally, diarrheal patients or animals are characterized by gut microbiota dysbiosis and pathogen infections may lead to diarrheal phenotypes. Of relevance, reprograming gut microbiota communities by dietary probiotics or fecal bacteria transplantation are widely introduced to treat or prevent diarrhea. In this review, we discussed the influence of the gut microbiota in the infection of diarrhea pathogens, and updated the research of reshaping the gut microbiota to prevent or treat diarrhea for the past few years. Together, gut microbiota manipulation is of great significance to the prevention and treatment of diarrhea, and further insight into the function of the gut microbiota will help to discover more anti-diarrhea probiotics.
The Type II Secretory System Mediates Phage Infection in Vibrio cholerae
Authors: Sun Huihui , Liu Ming , Fan Fenxia , Li Zhe , Fan Yufeng , Zhang Jingyun , Huang Yuanming , Li Zhenpeng , Li Jie , Xu Jialiang , Kan Biao
Published: April 2021

Attachment and specific binding to the receptor on the host cell surface is the first step in the process of bacteriophage infection. The lytic phage VP2 is used in phage subtyping of the Vibrio cholerae biotype El Tor of the O1 serogroup; however, its infection mechanism is poorly understood. In this study, we aimed to identify its receptor on V. cholerae. The outer membrane protein EpsD in the type II secretory system (T2SS) was found to be related to VP2-specific adsorption to V. cholerae, and the T2SS inner membrane protein EpsM had a role in successful VP2 infection, although it was not related to adsorption of VP2. The tail fiber protein gp20 of VP2 directly interacts with EpsD. Therefore, we found that in V. cholerae, in addition to the roles of the T2SS as the transport apparatus of cholera toxin secretion and filamentous phage release, the T2SS is also used as the receptor for phage infection and probably as the channel for phage DNA injection. Our study expands the understanding of the roles of the T2SS in bacteria.
The Building Blocks of Antimicrobial Resistance in Pseudomonas aeruginosa: Implications for Current Resistance-Breaking Therapies
Authors: Langendonk R. Frèdi , Neill Daniel R. , Fothergill Joanne L.
Published: April 2021

P. aeruginosa is classified as a priority one pathogen by the World Health Organisation, and new drugs are urgently needed, due to the emergence of multidrug-resistant (MDR) strains. Antimicrobial-resistant nosocomial pathogens such as P. aeruginosa pose unwavering and increasing threats. Antimicrobial stewardship has been a challenge during the COVID-19 pandemic, with a majority of those hospitalized with SARS-CoV2 infection given antibiotics as a safeguard against secondary bacterial infection. This increased usage, along with increased handling of sanitizers and disinfectants globally, may further accelerate the development and spread of cross-resistance to antibiotics. In addition, P. aeruginosa is the primary causative agent of morbidity and mortality in people with the life-shortening genetic disease cystic fibrosis (CF). Prolonged periods of selective pressure, associated with extended antibiotic treatment and the actions of host immune effectors, results in widespread adaptive and acquired resistance in P. aeruginosa found colonizing the lungs of people with CF. This review discusses the arsenal of resistance mechanisms utilized by P. aeruginosa, how these operate under high-stress environments such as the CF lung and how their interconnectedness can result in resistance to multiple antibiotic classes. Intrinsic, adaptive and acquired resistance mechanisms will be described, with a focus on how each layer of resistance can serve as a building block, contributing to multi-tiered resistance to antimicrobial activity. Recent progress in the development of anti-resistance adjuvant therapies, targeting one or more of these building blocks, should lead to novel strategies for combatting multidrug resistant P. aeruginosa. Anti-resistance adjuvant therapy holds great promise, not least because resistance against such therapeutics is predicted to be rare. The non-bactericidal nature of anti-resistance adjuvants reduce the selective pressures that drive resistance. Anti-resistance adjuvant therapy may also be advantageous in facilitating efficacious use of traditional antimicrobials, through enhanced penetration of the antibiotic into the bacterial cell. Promising anti-resistance adjuvant therapeutics and targets will be described, and key remaining challenges highlighted. As antimicrobial stewardship becomes more challenging in an era of emerging and re-emerging infectious diseases and global conflict, innovation in antibiotic adjuvant therapy can play an important role in extending the shelf-life of our existing antimicrobial therapeutic agents.
Working Across Faultlines—Assessing Intersubgroup Communication in Teams
Authors: Straube Julia , Kauffeld Simone
Published: April 2021

Communication between different subgroups is essential to group success, as different perspectives and knowledge need to be integrated. Especially when subgroups form due to faultlines, hypothetical dividing lines splitting a group into homogeneous subgroups, the resulting subgroups are vulnerable to negative intergroup processes. In this article, we evaluate different methods that have been used to trace communication between faultline-based subgroups and discuss challenges that researchers face when applying those methods. We further present the faultline communication index (FCI) as a novel approach to meet those challenges. We combine techniques from social network analysis with a behavioral process approach to trace communication processes between subgroups and provide scholars with tools to integrate in their own research. We illustrate this approach by observing and coding real time interactions in 29 organizational meetings. Results show that although functional faultline strength does not impact information exchange between subgroups, intersubgroup interactions positively relate to the quality of action plans defined at the end of a meeting. Managers and practitioners who work with diverse teams can be given guidance on how communication between subgroups evolves and how it can be shaped to become more effective. We further discuss implications for future research on communication between subgroups.
Conserving an Endangered Canid: Assessing Distribution, Habitat Protection, and Connectivity for the Dhole (Cuon alpinus) in Bhutan
Authors: Thinley Phuntsho , Rajaratnam Rajanathan , Kamler Jan F. , Wangmo Cheten
Published: April 2021

Most canids face population declines and range contractions worldwide. Although the dhole (Cuon alpinus) is widely distributed across 10 countries in South and Southeast Asia, limited studies exist on this species. Despite its globally “Endangered” status and ecological role as an apex predator, assessments on its distribution are limited to a few landscapes and countries. This explains the lack of a dhole-specific species conservation plan in most range countries, including Bhutan where no current population estimate exists. The species has also recovered from a country-wide poisoning campaign in the 1970s and 80s. In this study, we determine the dhole's distribution pattern and assess the protection and connectivity of dhole habitat in Bhutan. We anticipated dholes to be extant within their habitat well-represented in protected areas (PAs) and biological corridors (BCs). We used 721 georeferenced dhole occurrence records and eight environmental variables in MaxEnt software to model potential dhole distribution and habitat suitability. The model output was overlaid on the spatial layers of PAs and BCs to assess habitat protection and connectivity. As anticipated, we found the dhole widely distributed in all districts, PAs, and BCs in Bhutan. Dholes were recorded at the highest elevation range limit of 4,980 m above sea level, which overlapped with the “Vulnerable” snow leopard (Panthera uncia). Our model identified 72% (27,634 km2) of the country as suitable areas for dholes, of which, 31% (11,899 km2) was highly suitable and 41% (15,735 km2) was moderately suitable. Contrary to our expectation, PAs and BCs encompassed only 29% (8,046 km2) and 12% (3,185 km2) of suitable areas for dholes, respectively. A vast majority of the areas we deemed suitable for dholes currently remain unprotected, thus making dholes more vulnerable to human persecution and local extermination. We recommend adjusting PA boundaries to fully encompass suitable dhole habitat, and also advocate improved livestock husbandry to reduce dhole related livestock predation and minimize conflict, thereby ensuring its long-term survival in Bhutan.
A Juvenile Specimen of Archaeorhynchus Sheds New Light on the Ontogeny of Basal Euornithines
Authors: Foth Christian , Wang Shiying , Spindler Frederik , Lin Youhai , Yang Rui
Published: April 2021

The ontogenetic development of extant birds is characterized by rapid growth, bone fusion and an early onset of flight ability. In contrast, little is known about how these ontogenetic traits evolved in the bird stem lineage, and the available data pertains primarily to Enantiornithes. Here, we describe an almost complete skeleton of a juvenile euornithine bird (LNTU-WLMP-18) from the Early Cretaceous Jiufotang Formation (Aptian), which was discovered near Lamadong Town (Jianchang County, Liaoning, China). Despite its completeness, bone preservation is rather poor. Thus, to increase the contrast between bone tissue and matrix, we used cyan-red-based autofluorescence photography. The specimen is more or less articulated and exposed in ventral aspect. The jaws are edentulous, the coracoid bears a procoracoid process, and the ischium lacks a proximodorsal process. The pedal unguals are short and barely curved, indicating a ground-dwelling lifestyle. Feathers, including long primaries, are present as carbonized traces. Several characters indicate that LNTU-WLMP-18 is a juvenile: the bone surface has a coarsely striated texture and no fusion is evident between the carpals and metacarpals, between the tibia and the astragalus and calcaneum, or among the metatarsals. Although juvenile characters have the potential to impede accurate identification of the specimen, morphological comparisons and cladistic analysis identify LNTU-WLMP-18 as most likely referable to the basal euornithineArchaeorhynchus, which would make the specimen the first juvenile bird from the Jehol Group that could be assigned to a specific taxon. Based on its size and the incomplete ossification of the bone surface, LNTU-WLMP-18 represents the smallest and therefore youngest known individual of this genus. A statistical comparison of limb proportions shows that the forelimbs of LNTU-WLMP-18 are significantly shorter than the hindlimbs, while the forelimbs are longer than the hindlimbs in subadult and adult individuals. This is different from the situation in some Enantiornithes, in which the forelimbs exceed the length of the hindlimbs even in hatchlings. Similar to Enantiornithes,Archaeorhynchusprobably exhibit an early onset of flight ability, as indicated by the extensive wing plumage in LNTU-WLMP-18. Finally, the lack of gastroliths in the visceral cavity might indicate a dietary shift inArchaeorhynchusduring ontogeny. As a small-bodied, ground-dwelling, seed-eating bird with a precocial ontogeny,Archaeorhynchusfilled an ecological niche that later allowed early crown birds to survive the K-Pg mass extinction.
The Environment at Lake El’gygytgyn Area (Northeastern Russian Arctic) Prior to and After the Meteorite Impact at 3.58 Ma
Authors: Andreev Andrei , Dietze Elisabeth , Glushkova Olga , Smirnov Vladimir , Wennrich Volker , Melles Martin
Published: April 2021

Upper Pliocene sediments from a number of fluvial outcrops in central Chukotka, northeastern Russian Arctic, along the Enmyvaam, Mechekrynnetveem, and Chanuvenvaam Rivers, have been newly studied for pollen, non-pollen-palynomorphs and, for the first time for Pliocene sediments in Eurasia, charcoals. The sediments have survived the El’gygytgyn meteorite impact event at ∼3.58 Ma. The stratigraphy of the studied outcrops suggests that the lowermost sediments were accumulated shortly before the impact event, between ∼3.60 and 3.58 Ma. At that time, coniferous forests with spruces, pines, firs, birches, larches, and alders dominated in the area. Some relatively thermophilic broad-leaved taxa (Corylus, Carpinus, Ulmus, and Myrica) might also have grown in local forests. Summer temperatures were at least 10°C warmer than today. Charcoal concentrations and composition suggest the presence of high intensity fires. Periods of rather wet climate and soil conditions are marked by common shrubby and boggy habitats with ericaceous plants and Sphagnum, and are associated with less, and probably low-intensity surface fires with less charcoal. The impact event caused widespread fires reflected by up to 4 times higher charcoal concentrations in the sediments. The sediments found above the so-called “chaotic horizon” (sediments accumulated synchronously or very shortly after the impact event) contain late Pliocene pollen assemblages comparable to those in Lake El’gygytgyn, reflecting that pine-spruce forests with some firs, birches, larches, and alder dominated in the study area. Some thermophilic taxa might also still have grown in the area. However, the age control for the sediments above the so-called chaotic horizon is poor. The uppermost sediments from the studied sections can be attributed with certainty to the Late Pleistocene and Holocene according to their stratigraphic positions and pollen assemblages. The combined pollen and charcoal analysis allowed correlating hardly datable fluvial sediments and points to varying fire regimes in warmer-than-present climates, when forest extended further north compared to today.
Interleukin-35 Is Involved in Angiogenesis/Bone Remodeling Coupling Through T Helper 17/Interleukin-17 Axis
Authors: Zhang Hui , Li Yuxuan , Yuan Lin , Yao Lutian , Yang Jie , Xia Liping , Shen Hui , Lu Jing
Published: April 2021

Objective

Osteoporosis is a common metabolic bone disease mainly involving bone remodeling and blood vessels. The current study aimed to explore the suppressive role of interleukin (IL)-35 in nuclear factor kappa-B ligand receptor activator (RANKL) and macrophage colony stimulating factor (M-CSF)-induced osteoclastogenesis and angiogenesis in osteoclasts.

Methods

Osteoclasts differentiation were induced by incubation of mouse leukemic monocyte/macrophage cell line RAW264.7 cells in the presence of RANKL and M-CSF and was assessed with tartrate-resistant acid phosphatase (TRAP) staining assay. The viability and apoptosis of RAW264.7 was measured using CCK-8 assay and flow cytometry, respectively. The expression of angiogenic genes and proteins were measured using RT-PCR, Western blots and ELISA. The inhibition of Th17/IL-17 axis was examined using plumbagin, which was demonstrated as an IL-17A related signaling pathway inhibitor.

Results

IL-35 inhibited the viability of RAW264.7 cells and promoted the apoptosis of RAW264.7 cells in a dose-dependent manner. Furthermore, IL-35 dose-dependently suppressed the expression of angiogenic markers including VEGF and its receptor. The suppressive effect of IL-35 was confirmed through the activation of Th17/IL-17 axis.

Conclusions

We demonstrated for the first time the immuno-suppressive function of IL-35 on RANKL and M-CSF-induced osteoclastogenesis and angiogenesis through Th17/IL-17 axis. Therapeutic approach involving augmentation of IL-35 regulatory response may serve as a novel treatment option for osteoporosis, especially by suppressing bone resorption and angiogenesis.
Ag-Coated Cu/Polylactic Acid Composite Filament for Lithium and Sodium-Ion Battery Current Collector Three-Dimensional Printing via Thermoplastic Material Extrusion
Authors: Maurel Alexis , Kim Hyeonseok , Russo Roberto , Grugeon Sylvie , Armand Michel , Panier Stephane , Dupont Loic
Published: April 2021

This article focuses on the development of polylactic acid– (PLA-) based thermoplastic composite filament for its use, once 3D printed via thermoplastic material extrusion (TME), as current collector at the negative electrode side of a lithium-ion battery or sodium-ion battery. High electronic conductivity is achieved through the introduction of Ag-coated Cu charges, while appropriate mechanical performance to allow printability was maintained through the incorporation of poly(ethylene glycol) dimethyl ether average Mn ∼ 500 (PEGDME500) as a plasticizer into the PLA polymer matrix. Herein, thermal, electrical, morphological, electrochemical, and printability characteristics are discussed thoroughly. While Ag-Li alloy formation is reported at 0.1V upon cycling, its use with active materials such as Li4Ti5O12 (LTO) or Li2-terephthalate (Li2TP) operating at a plateau at higher potential is demonstrated. Furthermore, its ability to be used with negative electrode active material of sodium-ion battery technology in a wide potential window is demonstrated.
Comparing Multi-Criteria Decision-Making Methods for the Assessment of Flow Release Scenarios From Small Hydropower Plants in the Alpine Area
Authors: Vassoney Erica , Mammoliti Mochet Andrea , Desiderio Erika , Negro Giovanni , Pilloni Maria Gabriella , Comoglio Claudio
Published: April 2021

Growing energy demand and targets for reducing greenhouse gas emissions are driving a significant hydropower (HP) generation expansion in the Alpine area. However, despite its advantages, HP implementation causes several impacts on the ecological status of river systems and the preservation of characteristic landscapes. The use of decision-making tools, like multi-criteria decision-making (MCDM) methods, can provide helpful support to achieve more sustainable solutions for complex water management problems. In Aosta Valley (NW Italy), an MCDM experimental approach is being applied to define the optimal environmental flow scenario to be released by HP plants, in an attempt to balance energy production needs, economic profitability and environmental safeguard. Four criteria are considered (energy, environment and fishing, landscape, economy) and key stakeholders are involved in the entire decision-making process. However, there is a need to test also other MCDM methodologies in order to understand if an alternative approach could be more suitable for future, more complex, HP management decisions. Therefore, in this paper, seven different MCDM methods are applied to an existing small run-of-the-river HP plant for the selection of the optimal flow release scenario, i.e., SAW, WPM, AHP, TOPSIS, VIKOR, ELECTRE III, and the initially adopted method, SHARE MCA. The results obtained with the application of the different MCDM methods are investigated and statistically compared. The strengths and weaknesses of the different methodological approaches are also discussed. Based on the comparative results and the consequent evaluations, SHARE MCA, WPM, and VIKOR appear to have the most interesting characteristics in terms of overall feasibility.
Mammal Persistence Along Riparian Forests in Western India Within a Hydropower Reservoir 55 Years Post Construction
Authors: Jelil Shah Nawaz , Gaykar Avinash , Girkar Natasha , Ben Clement , Hayward Matt W. , Krishnamurthy Ramesh
Published: April 2021

While the negative impacts of dam construction on downstream river stretches and riparian forests are well studied, the status of wildlife presence and persistence in upstream reservoir deltas is virtually unknown. We investigated the drivers of terrestrial mammal occupancy and persistence along riparian forests of Koyna reservoir in western India 55 years after its construction. We adopted a catchment-wide field design grounded in the river continuum concept and sampled different stream orders within the reservoir. Camera traps, nested in an occupancy modeling framework, were deployed across 72 riparian sites and replicated for four seasons across all stream types. We recorded a total of nineteen species of terrestrial mammals during the study period. Multi-season occupancy models revealed three key patterns of mammal persistence: (a) ungulates were more frequently photo-captured in riparian forests; gaur and wild pig had the highest proportions of the total sampled area (0.84 ± 0.12 SE; 0.77 ± 0.07 SE, respectively); (b) small-sized ungulates were more vulnerable to local extinction than large-bodied ungulates; extinction probability was highest for barking deer (0.59 ± 0.07) and lowest for sambar (0.15 ± 0.07); and (c) distance from stream played major roles in determining mammal detection. Riparian forests are fundamentally important to ecosystem functioning and biodiversity conservation, and using the data from this study, managers can plan to sustain high mammal persistence along riparian forests at Koyna reservoir or similar Indian reserves. Further, our robust sampling approach, grounded in the terrestrial-riverine continuum concept, can be applied globally to understand species assemblages, aiding in multi-landscape and wildlife management planning.
Genomic Prediction Using Bayesian Regression Models With Global–Local Prior
Authors: Shi Shaolei , Li Xiujin , Fang Lingzhao , Liu Aoxing , Su Guosheng , Zhang Yi , Luobu Basang , Ding Xiangdong , Zhang Shengli
Published: April 2021

Bayesian regression models are widely used in genomic prediction for various species. By introducing the global parameter τ, which can shrink marker effects to zero, and the local parameter λk, which can allow markers with large effects to escape from the shrinkage, we developed two novel Bayesian models, named BayesHP and BayesHE. The BayesHP model uses Horseshoe+ prior, whereas the BayesHE model assumes local parameter λk, after a half-t distribution with an unknown degree of freedom. The performances of BayesHP and BayesHE models were compared with three classical prediction models, including GBLUP, BayesA, and BayesB, and BayesU, which also applied global–local prior (Horseshoe prior). To assess model performances for traits with various genetic architectures, simulated data and real data in cattle (milk production, health, and type traits) and mice (type and growth traits) were analyzed. The results of simulation data analysis indicated that models based on global–local priors, including BayesU, BayesHP, and BayesHE, performed better in traits with higher heritability and fewer quantitative trait locus. The results of real data analysis showed that BayesHE was optimal or suboptimal for all traits, whereas BayesHP was not superior to other classical models. For BayesHE, its flexibility to estimate hyperparameter automatically allows the model to be more adaptable to a wider range of traits. The BayesHP model, however, tended to be suitable for traits having major/large quantitative trait locus, given its nature of the “U” type-like shrinkage pattern. Our results suggested that auto-estimate the degree of freedom (e.g., BayesHE) would be a better choice other than increasing the local parameter layers (e.g., BayesHP). In this study, we introduced the global–local prior with unknown hyperparameter to Bayesian regression models for genomic prediction, which can trigger further investigations on model development.
Unearthing of Key Genes Driving the Pathogenesis of Alzheimer’s Disease via Bioinformatics
Authors: Zhao Xingxing , Yao Hongmei , Li Xinyi
Published: April 2021

Alzheimer’s disease (AD) is a neurodegenerative disease with unelucidated molecular pathogenesis. Herein, we aimed to identify potential hub genes governing the pathogenesis of AD. The AD datasets of GSE118553 and GSE131617 were collected from the NCBI GEO database. The weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and functional enrichment analysis were performed to reveal the hub genes and verify their role in AD. Hub genes were validated by machine learning algorithms. We identified modules and their corresponding hub genes from the temporal cortex (TC), frontal cortex (FC), entorhinal cortex (EC), and cerebellum (CE). We obtained 33, 42, 42, and 41 hub genes in modules associated with AD in TC, FC, EC, and CE tissues, respectively. Significant differences were recorded in the expression levels of hub genes between AD and the control group in the TC and EC tissues (P < 0.05). The differences in the expressions of FCGRT, SLC1A3, PTN, PTPRZ1, and PON2 in the FC and CE tissues among the AD and control groups were significant (P < 0.05). The expression levels of PLXNB1, GRAMD3, and GJA1 were statistically significant between the Braak NFT stages of AD. Overall, our study uncovered genes that may be involved in AD pathogenesis and revealed their potential for the development of AD biomarkers and appropriate AD therapeutics targets.
A Major and Stable Quantitative Trait Locus qSS2 for Seed Size and Shape Traits in a Soybean RIL Population
Authors: Kumawat Giriraj , Xu Donghe
Published: April 2021

Seed size and shape traits are important determinants of seed yield and appearance quality in soybean [Glycine max (L.) Merr.]. Understanding the genetic architecture of these traits is important to enable their genetic improvement through efficient and targeted selection in soybean breeding, and for the identification of underlying causal genes. To map seed size and shape traits in soybean, a recombinant inbred line (RIL) population developed from K099 (small seed size) × Fendou 16 (large seed size), was phenotyped in three growing seasons. A genetic map of the RIL population was developed using 1,485 genotyping by random amplicon sequencing-direct (GRAS-Di) and 177 SSR markers. Quantitative trait locus (QTL) mapping was conducted by inclusive composite interval mapping. As a result, 53 significant QTLs for seed size traits and 27 significant QTLs for seed shape traits were identified. Six of these QTLs (qSW8.1, qSW16.1, qSLW2.1, qSLT2.1, qSWT1.2, and qSWT4.3) were identified with LOD scores of 3.80–14.0 and R2 of 2.36%–39.49% in at least two growing seasons. Among the above significant QTLs, 24 QTLs were grouped into 11 QTL clusters, such as, three major QTLs (qSL2.3, qSLW2.1, and qSLT2.1) were clustered into a major QTL on Chr.02, named as qSS2. The effect of qSS2 was validated in a pair of near isogenic lines, and its candidate genes (Glyma.02G269400, Glyma.02G272100, Glyma.02G274900, Glyma.02G277200, and Glyma.02G277600) were mined. The results of this study will assist in the breeding programs aiming at improvement of seed size and shape traits in soybean.
Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India
Authors: Suri Deepti , Rikhi Rashmi , Jindal Ankur K. , Rawat Amit , Sudhakar Murugan , Vignesh Pandiarajan , Gupta Anju , Kaur Anit , Sharma Jyoti , Ahluwalia Jasmina , Bhatia Prateek , Khadwal Alka , Raj Revathi , Uppuluri Ramya , Desai Mukesh , Taur Prasad , Pandrowala Ambreen A. , Gowri Vijaya , Madkaikar Manisha R. , Lashkari Harsha Prasada , Bhattad Sagar , Kumar Harish , Verma Sanjeev , Imai Kohsuke , Nonoyama Shigeaki , Ohara Osamu , Chan Koon W. , Lee Pamela P. , Lau Yu Lung , Singh Surjit
Published: April 2021

Background

Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India.

Methods

Request to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed.

Results

In this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with ‘definite WAS’ were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months).

Conclusions

We report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.