bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism
Authors: Lindholm Päivi , Saarma Mart
Published: December 2021

Midbrain dopamine neurons deteriorate in Parkinson’s disease (PD) that is a progressive neurodegenerative movement disorder. No cure is available that would stop the dopaminergic decline or restore function of injured neurons in PD. Neurotrophic factors (NTFs), e.g., glial cell line-derived neurotrophic factor (GDNF) are small, secreted proteins that promote neuron survival during mammalian development and regulate adult neuronal plasticity, and they are studied as potential therapeutic agents for the treatment of neurodegenerative diseases. However, results from clinical trials of GDNF and related NTF neurturin (NRTN) in PD have been modest so far. In this review, we focus on cerebral dopamine neurotrophic factor (CDNF), an unconventional neurotrophic protein. CDNF delivered to the brain parenchyma protects and restores dopamine neurons in animal models of PD. In a recent Phase I-II clinical trial CDNF was found safe and well tolerated. CDNF deletion in mice led to age-dependent functional changes in the brain dopaminergic system and loss of enteric neurons resulting in slower gastrointestinal motility. These defects in Cdnf−/− mice intriguingly resemble deficiencies observed in early stage PD. Different from classical NTFs, CDNF can function both as an extracellular trophic factor and as an intracellular, endoplasmic reticulum (ER) luminal protein that protects neurons and other cell types against ER stress. Similarly to the homologous mesencephalic astrocyte-derived neurotrophic factor (MANF), CDNF is able to regulate ER stress-induced unfolded protein response (UPR) signaling and promote protein homeostasis in the ER. Since ER stress is thought to be one of the pathophysiological mechanisms contributing to the dopaminergic degeneration in PD, CDNF, and its small-molecule derivatives that are under development may provide useful tools for experimental medicine and future therapies for the treatment of PD and other neurodegenerative protein-misfolding diseases.
Infection of wild-type mice by SARS-CoV-2 B.1.351 variant indicates a possible novel cross-species transmission route
Authors: Pan Ting , Chen Ran , He Xin , Yuan Yaochang , Deng Xiaohui , Li Rong , Yan Haiping , Yan Shumei , Liu Jun , Zhang Yiwen , Zhang Xiantao , Yu Fei , Zhou Mo , Ke Changwen , Ma Xiancai , Zhang Hui
Published: December 2021

COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.
Long noncoding RNA GSEC promotes neutrophil inflammatory activation by supporting PFKFB3-involved glycolytic metabolism in sepsis
Authors: Liu Dadong , Sun Wen , Zhang Danying , Yu Zongying , Qin Weiting , Liu Yishu , Zhang Kai , Yin Jiangtao
Published: December 2021

Metabolic reprogramming is a hallmark of neutrophil activation in sepsis. LncRNAs play important roles in manipulating cell metabolism; however, their specific involvement in neutrophil activation in sepsis remains unclear. Here we found that 11 lncRNAs and 105 mRNAs were differentially expressed in three transcriptome datasets (GSE13904, GSE28750, and GSE64457) of gene expression in blood leukocytes and neutrophils of septic patients and healthy volunteers. After Gene Ontology biological process analysis and lncRNA–mRNA pathway network construction, we noticed that GSEC lncRNA and PFKFB3 were co-expressed and associated with enhanced glycolytic metabolism. Our clinical observations confirmed the expression patterns of GSEC lncRNA and PFKFB3 genes in neutrophils in septic patients. Performing in vitro experiments, we found that the expression of GSEC lncRNA and PFKFB3 was increased when neutrophils were treated with inflammatory stimuli. Knockdown and overexpression experiments showed that GSEC lncRNA was essential for mediating PFKFB3 mRNA expression and stability in neutrophil-like dHL-60 cells. In addition, we found that GSEC lncRNA-induced PFKFB3 expression was essential for mediating dHL-60 cell inflammatory cytokine expression. Performing mechanistic experiments, we found that glycolytic metabolism with PFKFB3 involvement supported inflammatory cytokine expression. In summary, our study uncovers a mechanism by which GSEC lncRNA promotes neutrophil inflammatory activation in sepsis by supporting glycolytic metabolism with PFKFB3.
Identification of mitochondrial RNA polymerase as a potential therapeutic target of osteosarcoma
Authors: Han Qi-cai , Zhang Xiang-yang , Yan Peng-hui , Chen Song-feng , Liu Fei-fei , Zhu Yun-Rong , Tian Qing
Published: December 2021

POLRMT (RNA polymerase mitochondrial) is essential for transcription of mitochondrial genome encoding components of oxidative phosphorylation process. The current study tested POLRMT expression and its potential function in osteosarcoma (OS). The Cancer Genome Atlas (TCGA) cohorts and Gene Expression Profiling Interactive Analysis (GEPIA) database both show that POLRMT transcripts are elevated in OS tissues. In addition, POLRMT mRNA and protein levels were upregulated in local OS tissues as well as in established and primary human OS cells. In different OS cells, shRNA-induced stable knockdown of POLRMT decreased cell viability, proliferation, migration, and invasion, whiling inducing apoptosis activation. CRISPR/Cas9-induced POLRMT knockout induced potent anti-OS cell activity as well. Conversely, in primary OS cells ectopic POLRMT overexpression accelerated cell proliferation and migration. In vivo, intratumoral injection of adeno-associated virus-packed POLRMT shRNA potently inhibited U2OS xenograft growth in nude mice. Importantly, levels of mitochondrial DNA, mitochondrial transcripts and expression of respiratory chain complex subunits were significantly decreased in U2OS xenografts with POLRMT shRNA virus injection. Together, POLRMT is overexpressed in human OS, promoting cell growth in vitro and in vivo. POLRMT could be a novel therapeutic target for OS.
A randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults
Authors: Haranaka Miwa , Baber James , Ogama Yoichiro , Yamaji Masako , Aizawa Masakazu , Kogawara Osamu , Scully Ingrid , Lagkadinou Eleni , Türeci Ӧzlem , Şahin Uğur , Dormitzer Philip R. , Gruber William C. , Lockhart Stephen
Published: December 2021

We report interim safety and immunogenicity findings from an ongoing phase 1/2 study of BNT162b2 in healthy Japanese adults. Participants were randomized 3:1 to receive 2 intramuscular injections of 30 μg BNT162b2 or placebo 21 days apart. Overall, 160 individuals were randomized: 119 received BNT162b2, and 41 received placebo. Participants were stratified by age: 20–64 years (n = 130) and 65–85 years (n = 30). More than 97% of BNT162b2 recipients received 2 doses. Local reactions and systemic events were generally transient and mild to moderate. Severe adverse events were uncommon; there were no serious adverse events. One month after dose 2, SARS-CoV-2 50% serum neutralizing geometric mean titers were 571 and 366, and geometric mean fold rises were 55.8 and 36.6, in the younger and older age groups, respectively. In summary, BNT162b2 has an acceptable safety profile and produces a robust immune response, regardless of age, in Japanese adults. (ClinicalTrials.gov, NCT04588480).
Increased labor losses and decreased adaptation potential in a warmer world
Authors: Parsons Luke A. , Shindell Drew , Tigchelaar Michelle , Zhang Yuqiang , Spector June T.
Published: December 2021

Working in hot and potentially humid conditions creates health and well-being risks that will increase as the planet warms. It has been proposed that workers could adapt to increasing temperatures by moving labor from midday to cooler hours. Here, we use reanalysis data to show that in the current climate approximately 30% of global heavy labor losses in the workday could be recovered by moving labor from the hottest hours of the day. However, we show that this particular workshift adaptation potential is lost at a rate of about 2% per degree of global warming as early morning heat exposure rises to unsafe levels for continuous work, with worker productivity losses accelerating under higher warming levels. These findings emphasize the importance of finding alternative adaptation mechanisms to keep workers safe, as well as the importance of limiting global warming.
Metabolic drug survey highlights cancer cell dependencies and vulnerabilities
Authors: Pemovska Tea , Bigenzahn Johannes W. , Srndic Ismet , Lercher Alexander , Bergthaler Andreas , César-Razquin Adrián , Kartnig Felix , Kornauth Christoph , Valent Peter , Staber Philipp B. , Superti-Furga Giulio
Published: December 2021

Interrogation of cellular metabolism with high-throughput screening approaches can unravel contextual biology and identify cancer-specific metabolic vulnerabilities. To systematically study the consequences of distinct metabolic perturbations, we assemble a comprehensive metabolic drug library (CeMM Library of Metabolic Drugs; CLIMET) covering 243 compounds. We, next, characterize it phenotypically in a diverse panel of myeloid leukemia cell lines and primary patient cells. Analysis of the drug response profiles reveals that 77 drugs affect cell viability, with the top effective compounds targeting nucleic acid synthesis, oxidative stress, and the PI3K/mTOR pathway. Clustering of individual drug response profiles stratifies the cell lines into five functional groups, which link to specific molecular and metabolic features. Mechanistic characterization of selective responses to the PI3K inhibitor pictilisib, the fatty acid synthase inhibitor GSK2194069, and the SLC16A1 inhibitor AZD3965, bring forth biomarkers of drug response. Phenotypic screening using CLIMET represents a valuable tool to probe cellular metabolism and identify metabolic dependencies at large.
The effect of COVID-19 vaccination in Italy and perspectives for living with the virus
Authors: Marziano Valentina , Guzzetta Giorgio , Mammone Alessia , Riccardo Flavia , Poletti Piero , Trentini Filippo , Manica Mattia , Siddu Andrea , Bella Antonino , Stefanelli Paola , Pezzotti Patrizio , Ajelli Marco , Brusaferro Silvio , Rezza Giovanni , Merler Stefano
Published: December 2021

COVID-19 vaccination is allowing a progressive release of restrictions worldwide. Using a mathematical model, we assess the impact of vaccination in Italy since December 27, 2020 and evaluate prospects for societal reopening after emergence of the Delta variant. We estimate that by June 30, 2021, COVID-19 vaccination allowed the resumption of about half of pre-pandemic social contacts. In absence of vaccination, the same number of cases is obtained by resuming only about one third of pre-pandemic contacts, with about 12,100 (95% CI: 6,600-21,000) extra deaths (+27%; 95% CI: 15–47%). Vaccination offset the effect of the Delta variant in summer 2021. The future epidemic trend is surrounded by substantial uncertainty. Should a pediatric vaccine (for ages 5 and older) be licensed and a coverage >90% be achieved in all age classes, a return to pre-pandemic society could be envisioned. Increasing vaccination coverage will allow further reopening even in absence of a pediatric vaccine.
A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus
Authors: Bhatia Bharti , Meade-White Kimberly , Haddock Elaine , Feldmann Friederike , Marzi Andrea , Feldmann Heinz
Published: December 2021

Kyasanur Forest disease virus (KFDV) is a tick-borne flavivirus endemic in India known to cause severe hemorrhagic and encephalitic disease in humans. In recent years, KFDV has spread beyond its original endemic zone raising public health concerns. Currently, there is no treatment available for KFDV but a vaccine with limited efficacy is used in India. Here, we generated two new KFDV vaccine candidates based on the vesicular stomatitis virus (VSV) platform. We chose the VSV-Ebola virus (VSV-EBOV) vector either with the full-length or a truncated EBOV glycoprotein as the vehicle to express the precursor membrane (prM) and envelope (E) proteins of KFDV (VSV-KFDV). For efficacy testing, we established a mouse disease model by comparing KFDV infections in three immunocompetent mouse strains (BALB/c, C57Bl/6, and CD1). Both vaccine vectors provided promising protection against lethal KFDV challenge in the BALB/c model following prime-only prime-boost and immunizations. Only prime-boost immunization with VSV-KFDV expressing full-length EBOV GP resulted in uniform protection. Hyperimmune serum derived from prime-boost immunized mice protected naïve BALB/c mice from lethal KFDV challenge indicating the importance of antibodies for protection. The new VSV-KFDV vectors are promising vaccine candidates to combat an emerging, neglected public health problem in a densely populated part of the world.
Cytokine autoantibodies are stable throughout the haematopoietic stem cell transplantation course and are associated with distinct biomarker and blood cell profiles
Authors: von Stemann Jakob Hjorth , Gjærde Lars Klingen , Haastrup Eva Kannik , Minculescu Lia , Brooks Patrick Terrence , Sengeløv Henrik , Hansen Morten Bagge , Ostrowski Sisse Rye
Published: December 2021

Cytokine-specific autoantibodies (c-aAbs) represent an emerging field in endogenous immunodeficiencies, and the immunomodulatory potential of c-aAbs is now well documented. Here, we investigated the hypothesis that c-aAbs affects inflammatory, immunoregulatory and injury-related processes and hence the clinical outcome of haematopoietic stem cell transplantation (HSCT). C-aAbs against IL-1α, IL-6, IL-10, IFNα, IFNγ and GM-CSF were measured in 131 HSCT recipients before and after (days + 7, + 14, + 28) HSCT and tested for associations with 33 different plasma biomarkers, leukocyte subsets, platelets and clinical outcomes, including engraftment, GvHD and infections. We found that c-aAb levels were stable over the course of HSCT, including at high titres, with few individuals seeming to acquire high-titre levels of c-aAbs. Both patients with stable and those with acquired high-titre c-aAb levels displayed significant differences in biomarker concentrations and blood cell counts pre-HSCT and at day 28, and the trajectories of these variables varied over the course of HSCT. No clinical outcomes were associated with high-titre c-aAbs. In this first study of c-aAbs in HSCT patients, we demonstrated that high-titre levels of c-aAb may both persist and emerge in patients over the course of HSCT and may be associated with altered immune biomarkers and cell profiles.
Water stress intensified the relation of seed color with lignan content and seed yield components in flax (Linum usitatissimum L.)
Authors: Zare Sara , Mirlohi Aghafakhr , Saeidi Ghodratollah , Sabzalian Mohammad R. , Ataii Ehsan
Published: December 2021

This study aimed to investigate the effect of yellow and brown seed coat color of flax on lignan content, seed yield, and yield components under two contrasting environments of non-stress and water stress conditions. The water stress environment intensified the discrimination between the two seed color groups as the yellow seeded families had lower values for seed yield components under the water stress. Heritability and the genetic advance for seed yield were significantly higher in brown-seeded families than those of yellow-seeded ones at water stress conditions. Secoisolariciresinol diglucoside (SDG) as the chief lignan in flaxseed was more abundant in yellow-seeded families under the non-stress environment but under water stress conditions, it increased in brown seeded families and exceeded from yellow ones. Considering that the brown and yellow seed color families were full sibs and shared a similar genetic background but differed in seed color, it is concluded that a considerable interaction exists between the flax seed color and moisture stress concerning its effect on seed yield and yield components and also the seed SDG content. Brown-seeded genotypes are probably preferred for cultivation under water stress conditions for better exploitation of flax agronomic and nutritional potentials.
Analysis of light-wave nonstaticity in the coherent state
Authors: Choi Jeong Ryeol
Published: December 2021

The characteristics of nonstatic quantum light waves in the coherent state in a static environment is investigated. It is shown that the shape of the wave varies periodically as a manifestation of its peculiar properties of nonstaticity like the case of the Fock-state analysis for a nonstatic wave. A belly occurs in the graphic of wave evolution whenever the wave is maximally displaced in the quadrature space, whereas a node takes place every time the wave passes the equilibrium point during its oscillation. In this way, a belly and a node appear in turn successively. Whereas this change of wave profile is accompanied by the periodic variation of electric and magnetic energies, the total energy is conserved. The fluctuations of quadratures also vary in a regular manner according to the wave transformation in time. While the resultant time-varying uncertainty product is always larger than (or, at least, equal to) its quantum-mechanically allowed minimal value ($$\hbar /2$$

ħ
/
2

), it is smallest whenever the wave constitutes a belly or a node. The mechanism underlying the abnormal features of nonstatic light waves demonstrated here can be interpreted by the rotation of the squeezed-shape contour of the Wigner distribution function in phase space.
Calibration of two validated SARS-CoV-2 pseudovirus neutralization assays for COVID-19 vaccine evaluation
Authors: Huang Yunda , Borisov Oleg , Kee Jia Jin , Carpp Lindsay N. , Wrin Terri , Cai Suqin , Sarzotti-Kelsoe Marcella , McDanal Charlene , Eaton Amanda , Pajon Rolando , Hural John , Posavad Christine M. , Gill Katherine , Karuna Shelly , Corey Lawrence , McElrath M. Juliana , Gilbert Peter B. , Petropoulos Christos J. , Montefiori David C.
Published: December 2021

Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization’s anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.
The effect of Propofol versus Dexmedetomidine as anesthetic agents for oocyte pick-up on in vitro fertilization (IVF) outcomes
Authors: Budak Özcan , Bostancı Mehmet Sühha , Tuna AyçaTaş , Toprak Veysel , Çakiroğlu Hüseyin , Gök Koray
Published: December 2021

This study aimed to evaluate the effects of propofol and dexmedetomidine over different timescales on the IVF outcomes for transvaginal oocyte retrieval (TVOR). Twenty-four rats included in the study were divided into two main groups and three subgroups were subjected to the ovulation induction process. Group 1 was administered propofol (100 mg/kg i.v.) and group 2 were administered dexmedetomidine (25 µg/kg i.p.) The oviduct collection procedure was completed within 15 min for subgroup Pro15min, Dex15min (n = 4), within 16 to 30 min for subgroup Pro30min, Dex30min (n = 4) and within 31 to 60 min for subgroup Pro60min, Dex60min (n = 4) after euthanasia. The total number of oocytes was counted. After in vitro fertilization, the number and quality of embryos were evaluated. The number of pups born were evaluated after embryo transfer. The embryo number, quality and pup count decreased as the administration time for propofol increased (p < 0.05). No statistically significant difference was found between the dexmedetomidine subgroups for embryo number, quality and pup count(p > 0.05). As the exposure time to propofol increased, the number and quality of embryos obtained, and the pup count, decreased. The use of dexmedetomidine had no negative impacts on the number of embryos, their quality or the number of pups.
Circulating microRNA-197-3p as a potential biomarker for asbestos exposure
Authors: Frontini Francesca , Bononi Ilaria , Torreggiani Elena , Di Mauro Giulia , Mazzoni Elisa , Stendardo Mariarita , Boschetto Piera , Libener Roberta , Guaschino Roberto , Grosso Federica , Guerra Giovanni , Martini Fernanda , Tognon Mauro
Published: December 2021

Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.
Common osteoporosis drug associated with increased rates of depression and anxiety
Authors: Keshishi Dro , Makunts Tigran , Abagyan Ruben
Published: December 2021

Osteoporosis affects over 10 million Americans over 50. Bisphosphonate therapy, mainly alendronate, is amongst the most prescribed treatments for the disease. The use of alendronate and other bisphosphonates has been associated with depressive symptoms in recent case reports. In this study we quantified this association by analyzing over 100,000 adverse events reports from the Food and Drug Administration Adverse Events Reporting System (FAERS) and the World Health Organization’s (WHO) global database for adverse drug reactions, ADRs, VigiAccess. We found that alendronate therapy is significantly associated with depression and anxiety when compared to other first-line osteoporosis treatments. The reported risk of depressive ADRs was found to be over 14-fold greater in patients taking alendronate under the age of 65 and over fourfold greater for patients over 65 compared to the control. Several hypotheses concerning the molecular mechanism of the observed association of alendronate and depressive symptoms were discussed.
Estimating the SARS-CoV-2 infected population fraction and the infection-to-fatality ratio: a data-driven case study based on Swedish time series data
Authors: Wacker Andreas , Jöud Anna , Bernhardsson Bo , Gerlee Philip , Gustafsson Fredrik , Soltesz Kristian
Published: December 2021

We demonstrate that finite impulse response (FIR) models can be applied to analyze the time evolution of an epidemic with its impact on deaths and healthcare strain. Using time series data for COVID-19-related cases, ICU admissions and deaths from Sweden, the FIR model gives a consistent epidemiological trajectory for a simple delta filter function. This results in a consistent scaling between the time series if appropriate time delays are applied and allows the reconstruction of cases for times before July 2020, when RT-PCR testing was not widely available. Combined with randomized RT-PCR study results, we utilize this approach to estimate the total number of infections in Sweden, and the corresponding infection-to-fatality ratio (IFR), infection-to-case ratio (ICR), and infection-to-ICU admission ratio (IIAR). Our values for IFR, ICR and IIAR are essentially constant over large parts of 2020 in contrast with claims of healthcare adaptation or mutated virus variants importantly affecting these ratios. We observe a diminished IFR in late summer 2020 as well as a strong decline during 2021, following the launch of a nation-wide vaccination program. The total number of infections during 2020 is estimated to 1.3 million, indicating that Sweden was far from herd immunity.
Conventional agriculture and not drought alters relationships between soil biota and functions
Authors: Birkhofer Klaus , Fliessbach Andreas , Gavín-Centol María Pilar , Hedlund Katarina , Ingimarsdóttir María , Jørgensen Helene Bracht , Kozjek Katja , Meyer Svenja , Montserrat Marta , Moreno Sara Sánchez , Laraño Jordi Moya , Scheu Stefan , Serrano-Carnero Diego , Truu Jaak , Kundel Dominika
Published: December 2021

Soil biodiversity constitutes the biological pillars of ecosystem services provided by soils worldwide. Soil life is threatened by intense agricultural management and shifts in climatic conditions as two important global change drivers which are not often jointly studied under field conditions. We addressed the effects of experimental short-term drought over the wheat growing season on soil organisms and ecosystem functions under organic and conventional farming in a Swiss long term trial. Our results suggest that activity and community metrics are suitable indicators for drought stress while microbial communities primarily responded to agricultural practices. Importantly, we found a significant loss of multiple pairwise positive and negative relationships between soil biota and process-related variables in response to conventional farming, but not in response to experimental drought. These results suggest a considerable weakening of the contribution of soil biota to ecosystem functions under long-term conventional agriculture. Independent of the farming system, experimental and seasonal (ambient) drought conditions directly affected soil biota and activity. A higher soil water content during early and intermediate stages of the growing season and a high number of significant relationships between soil biota to ecosystem functions suggest that organic farming provides a buffer against drought effects.
Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2
Authors: Kumon Kazuki , Afify Said M. , Hassan Ghmkin , Ueno Shunsuke , Monzur Sadia , Nawara Hend M. , Quora Hagar A. Abu , Sheta Mona , Xu Yanning , Fu Xiaoying , Zahra Maram H. , Seno Akimasa , Seno Masaharu
Published: December 2021

Cancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl2. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl2, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl2 induced significant accumulation of HIF-1α changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34+ and c-kit+ was immunologically detected in the presence of CoCl2. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.
The effect of the use of commercial tempeh starter on the diversity of Rhizopus tempeh in Indonesia
Authors: Sjamsuridzal Wellyzar , Khasanah Mangunatun , Febriani Rela , Vebliza Yura , Oetari Ariyanti , Santoso Iman , Gandjar Indrawati
Published: December 2021

At present, only a singleRhizopusspecies,R. microsporus, can be found in fresh tempeh produced in Java, Indonesia. The loss of diversity ofRhizopusin tempeh has been associated with the widespread use of commercial tempeh starter in Indonesia since the 2000s. However, the identities of the previousRhizopusstrains associated with tempeh, which have been preserved in a culture collection in Indonesia, have not been verified. The present study aimed to verify the identities of 22Rhizopusstrains isolated from tempeh produced using the traditional tempeh starters from the 1960s to the 2000s. Phylogenetic analysis based on the ITS regions in the rRNA gene sequence data, revealed that theRhizopusstrains belonged to the speciesR. arrhizus(five strains);R. delemar(14 strains); andR. microsporus(three strains).Verification of the identities of theseRhizopusstrains in the present study confirmed the loss of diversity ofRhizopusspecies in tempeh produced in Indonesia, particularly in Java. Our findings confirmed that the morphological changes inRhizopusspecies isolated from tempeh as a result of centuries of domestication.
Returning to work after a sickness absence due to cancer: a cohort study of salaried workers in Catalonia (Spain)
Authors: Ayala-Garcia Amaya , Serra Laura , Hernando-Rodriguez Julio C. , Benavides Fernando G.
Published: December 2021

Cancer incidence and survival rates have increased in the last decades and as a result, the number of working age people diagnosed with cancer who return to work. In this study the probability of accumulating days of employment and employment participation trajectories (EPTs) in a sample of salaried workers in Catalonia (Spain) who had a sickness absence (SA) due to cancer were compared to salaried workers with SA due to other diagnoses or without SA. Each individual with SA due to cancer between 2012 and 2015 was matched by age, sex, and onset of time at risk to a worker with SA due to other diagnoses and another worker without SA. Accumulated days of employment were measured, and negative binomial models were applied to assess differences between comparison groups. Latent class models were applied to identify EPTs and multinomial regression models to analyse the probability of belonging to one EPT of each group. Men and women without SA or with SA due to other diagnoses had at least a 9% higher probability of continuing in employment compared to workers who had a SA due to cancer, especially among men without SA (adjusted IRR 1.27, 95% CI 1.06‒1.53). Men without SA had the highest probability of having high stable EPT compared to workers who had a SA due to cancer (adjusted RRR 3.21, 95% CI 1.87‒5.50). Even though workers with SA due to cancer continue working afterwards, they do it less often than matched controls and with a less stable employment trajectory. Health and social protection systems should guaranty cancer survivors the opportunity to continue voluntary participation in the labour market.
Transcriptomic adaptation during skeletal muscle habituation to eccentric or concentric exercise training
Authors: Willis Craig R. G. , Deane Colleen S. , Ames Ryan M. , Bass Joseph J. , Wilkinson Daniel J. , Smith Kenneth , Phillips Bethan E. , Szewczyk Nathaniel J. , Atherton Philip J. , Etheridge Timothy
Published: December 2021

Eccentric (ECC) and concentric (CON) contractions induce distinct muscle remodelling patterns that manifest early during exercise training, the causes of which remain unclear. We examined molecular signatures of early contraction mode-specific muscle adaptation via transcriptome-wide network and secretome analyses during 2 weeks of ECC- versus CON-specific (downhill versus uphill running) exercise training (exercise ‘habituation’). Despite habituation attenuating total numbers of exercise-induced genes, functional gene-level profiles of untrained ECC or CON were largely unaltered post-habituation. Network analysis revealed 11 ECC-specific modules, including upregulated extracellular matrix and immune profiles plus downregulated mitochondrial pathways following untrained ECC. Of 3 CON-unique modules, 2 were ribosome-related and downregulated post-habituation. Across training, 376 ECC-specific and 110 CON-specific hub genes were identified, plus 45 predicted transcription factors. Secreted factors were enriched in 3 ECC- and/or CON-responsive modules, with all 3 also being under the predicted transcriptional control of SP1 and KLF4. Of 34 candidate myokine hubs, 1 was also predicted to have elevated expression in skeletal muscle versus other tissues: THBS4, of a secretome-enriched module upregulated after untrained ECC. In conclusion, distinct untrained ECC and CON transcriptional responses are dampened after habituation without substantially shifting molecular functional profiles, providing new mechanistic candidates into contraction-mode specific muscle regulation.
An integrative genomic and phenomic analysis to investigate the nature of plant species in Escallonia (Escalloniaceae)
Authors: Jacobs Sarah J. , Grundler Michael C. , Henriquez Claudia L. , Zapata Felipe
Published: December 2021

What we mean by species and whether they have any biological reality has been debated since the early days of evolutionary biology. Some biologists even suggest that plant species are created by taxonomists as a subjective, artificial division of nature. However, the nature of plant species has been rarely tested critically with data while ignoring taxonomy. We integrate phenomic and genomic data collected across hundreds of individuals at a continental scale to investigate this question inEscallonia(Escalloniaceae), a group of plants which includes 40 taxonomic species (the species proposed by taxonomists). We first show that taxonomic species may be questionable as they match poorly to patterns of phenotypic and genetic variation displayed by individuals collected in nature. We then use explicit statistical methods for species delimitation designed for phenotypic and genomic data, and show that plant species do exist inEscalloniaas an objective, discrete property of nature independent of taxonomy. We show that such species correspond poorly to current taxonomic species ($$< 20\%$$<20%) and that phenomic and genomic data seldom delimit congruent entities ($$< 20\%$$<20%). These discrepancies suggest that evolutionary forces additional to gene flow can maintain the cohesion of species. We propose that phenomic and genomic data analyzed on an equal footing build a broader perspective on the nature of plant species by helping delineate different ‘types of species’. Our results caution studies which take the accuracy of taxonomic species for granted and challenge the notion of plant species without empirical evidence. Note: A version of the complete manuscript in Spanish is available in the Supplemental Materials.
Association of loss of spleen visualization on whole-body diffusion-weighted imaging with prognosis and tumor burden in patients with multiple myeloma
Authors: Terao Toshiki , Machida Youichi , Tateishi Ukihide , Tsushima Takafumi , Narita Kentaro , Ikeda Daisuke , Fukumoto Ami , Kuzume Ayumi , Tabata Rikako , Miura Daisuke , Takeuchi Masami , Matsue Kosei
Published: December 2021

This study investigated the clinical significance of loss of spleen visualization (LSV) on whole-body diffusion-weighted imaging (WB-DWI) in patients with multiple myeloma (MM). The WB-DWI of 96 patients with newly diagnosed MM (NDMM) and 15 patients with smoldering MM (sMM) were retrospectively reviewed. LSV was observed in 56 patients with NDMM (58.3%) and 1 patient with sMM (6.7%). Patients with NDMM with LSV had a higher median infiltration of bone marrow plasma cells (80.0% vs. 50.0%, p < 0.001) and median total diffusion volume (median; 540.2 vs. 137.0 mL, p = 0.003) than patients without LSV. Patients with LSV had a lower spleen-to-spinal cord ratio (0.36 vs. 0.96, p < 0.001) and worse 2-year overall survival (OS) (84.6% vs. 100%, p = 0.032). Patients who did not recover spleen visualization during treatment had a worse prognosis, even when they obtained very good partial response (median progression-free survival: 13.2 months). Spleen histopathological findings revealed higher cellularity and diffuse myeloma cell infiltration in a patient with LSV and splenic amyloidosis without extramedullary hematopoiesis in a patient without LSV. Therefore, LSV indicates worse prognosis for patients with MM, even when the patient responds to treatment. Further studies are warranted to clarify the immunological role of spleen in MM.
The minor T allele of the MUC5B promoter rs35705950 associated with susceptibility to idiopathic pulmonary fibrosis: a meta-analysis
Authors: Wu Xiaozheng , Li Wen , Luo Zhenliang , Chen Yunzhi
Published: December 2021

MUC5B promoter rs35705950 T/G gene polymorphism has been associated with the risk of IPF, but the influence of this relationship varies among different populations. In the past 2 years, there were new clinical studies with different results, but none of them reached unified conclusions. Therefore, this study further included the latest case–control studies, integrated their results and carried out meta-analysis on them to draw reliable conclusions. PubMed, EMBASE, CNKI, Wanfang database and VIP Chinese science were searched by a computer to collect the related literatures of MUC5B gene polymorphism and IPF susceptibility published before June 15, 2021. The first author, year of publication, diagnostic criteria and gene frequency were extracted after screened them. Forest plot was drawn and the trial sequential analysis (TSA) was carried out to confirm the stability of the meta-analysis results. Registration number: CRD42021272940. A total of 24 case–control studies (13 studies on the Caucasian, 7 studies on the Asian and 4 studies on the mixed population), and a total of 6749 IPF patients and 13,898 healthy controls were included in this study. The T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B promoter rs35705950 T/G polymorphism were associated with IPF risk in all populations, and the effect values were ([OR] 4.12, 95% CI [3.64, 4.67]), ([OR] 10.12, 95% CI [7.06, 14.49]), ([OR] 4.84, 95% CI [3.85, 6.08]), ([OR] 4.84, 95% CI [3.79, 6.19]) and ([OR] 5.11, 95% CI [4.02, 6.49]), respectively. The results of TSA confirmed the stability of the results. Subgroup analysis showed that T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B polymorphism were associated with IPF risk in Caucasian population. The effect values were ([OR] 4.50, 95% CI [3.93, 5.16]), ([OR] 10.98, 95% CI [7.59, 15.89]), ([OR] 6.27, 95% CI [5.37, 7.32]), ([OR] 6.30, 95% CI [5.19, 7.64]) and ([OR] 5.15, 95% CI [4.01, 6.61]), respectively. Similar results were also found in Asian and mixed populations. The association strength of the minor T allele in the Caucasian was more significant than that of the Asian population ([OR] 4.50 vs. [OR] 2.39), and the association strength of all genetic models carrying "T" was more significant than that of the Asian population ([OR] 10.98 vs. [OR] 4.29). In Caucasian, Asian and mixed populations, T minor allele carriers were more likely to be susceptible to pulmonary fibrosis, and TT genotype carriers were more likely to be susceptible to IPF than GT genotype carriers. The association between IPF and Caucasian population with minor T allele and all "T" genetic model was more significant than that of Asian population.
Encoding of facial features by single neurons in the human amygdala and hippocampus
Authors: Cao Runnan , Li Xin , Brandmeir Nicholas J. , Wang Shuo
Published: December 2021

Faces are salient social stimuli that attract a stereotypical pattern of eye movement. The human amygdala and hippocampus are involved in various aspects of face processing; however, it remains unclear how they encode the content of fixations when viewing faces. To answer this question, we employed single-neuron recordings with simultaneous eye tracking when participants viewed natural face stimuli. We found a class of neurons in the human amygdala and hippocampus that encoded salient facial features such as the eyes and mouth. With a control experiment using non-face stimuli, we further showed that feature selectivity was specific to faces. We also found another population of neurons that differentiated saccades to the eyes vs. the mouth. Population decoding confirmed our results and further revealed the temporal dynamics of face feature coding. Interestingly, we found that the amygdala and hippocampus played different roles in encoding facial features. Lastly, we revealed two functional roles of feature-selective neurons: 1) they encoded the salient region for face recognition, and 2) they were related to perceived social trait judgments. Together, our results link eye movement with neural face processing and provide important mechanistic insights for human face perception.
Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates
Authors: Simone Davide , Penkava Frank , Ridley Anna , Sansom Stephen , Al-Mossawi M. Hussein , Bowness Paul
Published: December 2021

Regulatory T cells (Tregs) play an important role in controlling inflammation and limiting autoimmunity, but their phenotypes at inflammatory sites in human disease are poorly understood. We here analyze the single-cell transcriptome of >16,000 Tregs obtained from peripheral blood and synovial fluid of two patients with HLA-B27+ ankylosing spondylitis and three patients with psoriatic arthritis, closely related forms of inflammatory spondyloarthritis. We identify multiple Treg clusters with distinct transcriptomic profiles, including, among others, a regulatory CD8+subset expressing cytotoxic markers/genes, and a Th17-likeRORC+ Treg subset characterized by IL-10 and LAG-3 expression. Synovial Tregs show upregulation of interferon signature and TNF receptor superfamily genes, and marked clonal expansion, consistent with tissue adaptation and antigen contact respectively. Individual synovial Treg clones map to different clusters indicating cell fate divergence. Finally, we demonstrate that LAG-3 directly inhibits IL-12/23 and TNF secretion by patient-derived monocytes, a mechanism with translational potential in SpA. Our detailed characterization of Tregs at an important inflammatory site illustrates the marked specialization of Treg subpopulations.
Berry paramagnetism in the Dirac semimetal ZrTe5
Authors: Ji Sanghyun , Lee Sang-Eon , Jung Myung-Hwa
Published: December 2021

Dirac matters have attracted a lot of interest due to their unique band structure with linear band dispersions, which have great potential for technological applications. Recently, three-dimensional Dirac and Weyl semimetals have invoked distinctive phenomena originating from a non-trivial Berry phase. In this study, we prepare single crystals of TixZr1-xTe5 with a highly anisotropic Fermi surface. Our detailed electrical transport measurements reveal that the crystals show the Lifshitz transition, and Ti doping induces a band shift. Further quantum oscillation analyses demonstrate that the TixZr1-xTe5 crystals are 3D Dirac semimetals. Additionally, we observed a minimum temperature-dependent magnetic susceptibility, which is close to a peak position of electrical resistivity. This observation is interpreted in terms of the Berry paramagnetism. Our finding paves the way to determine a band topology by magnetism and also provides a platform to apply the Berry magnetism to Dirac semimetals.
Observation of a flat band and bandgap in millimeter-scale twisted bilayer graphene
Authors: Sato Keiju , Hayashi Naoki , Ito Takahiro , Masago Noriyuki , Takamura Makoto , Morimoto Mitsuru , Maekawa Takuji , Lee Doyoon , Qiao Kuan , Kim Jeehwan , Nakagahara Keisuke , Wakabayashi Katsunori , Hibino Hiroki , Norimatsu Wataru
Published: December 2021

Magic-angle twisted bilayer graphene, consisting of two graphene layers stacked at a special angle, exhibits superconductivity due to the maximized density of states at the energy of the flat band. Generally, experiments on twisted bilayer graphene have been performed using micrometer-scale samples. Here we report the fabrication of twisted bilayer graphene with an area exceeding 3 × 5 mm2 by transferring epitaxial graphene onto another epitaxial graphene, and observation of a flat band and large bandgap using angle-resolved photoemission spectroscopy. Our results suggest that the substrate potential induces both the asymmetrical doping in large angle twisted bilayer graphene and the electron doped nature of the flat band in magic-angle twisted bilayer graphene.
Labelling stem cells with a nanoprobe for evaluating the homing behaviour in facial nerve injury repair
Authors: Tang Na , Wang Xueyi , Zhu Jin , Sun Kang , Li Shiting , Tao Ke
Published: December 2021

The necessity of a chemokine in the cell therapy of facial nerve injury was demonstrated by labelling the stem cells with a nanoprobe.
Ultrathin nanosheet-assembled nickel-based metal–organic framework microflowers for supercapacitor applications
Authors: Wang Cong-Huan , Zhang Da-Wei , Liu Shude , Yamauchi Yusuke , Zhang Fei-Bao , Kaneti Yusuf Valentino
Published: December 2021

Herein, we propose a solvent-assisted approach for preparing Ni-MOF microflowers with high specific capacitance and excellent rate capability as electrode materials for supercapacitors.
Long-life zinc electrodes achieved by oxygen plasma functionalization
Authors: Qiu Minghui , Liu Hongqi , Luo Jinbin , Tawiah Benjamin , Fu Shaohai , Jia Hao
Published: December 2021

A facile oxygen plasma treatment strategy is proposed to promote zinc dendrite inhibition by modifying the surface oxygen functional groups.
Room temperature HFIP/Ag-promoted palladium-catalyzed C–H functionalization of benzothiazole with iodoarenes
Authors: Kori Santosh , Bhujbal Yuvraj , Vadagaonkar Kamlesh , Kapdi Anant R. , Kommyreddy Saidurga Prasad , Gharpure Santosh J.
Published: December 2021

A versatile synthetic protocol involving the room temperature direct arylation of benzothiazole with a wide variety of iodoarenes under Ag-promoted Pd-catalyzed conditions in HFIP as the reaction solvent has been presented.