bluuebunny/crossref_metadata_2025 huggingface dataset:
Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice
Authors: Kesner Andrew J. , Shin Rick , Calva Coleman B. , Don Reuben F. , Junn Sue , Potter Christian T. , Ramsey Leslie A. , Abou-Elnaga Ahmed F. , Cover Christopher G. , Wang Dong V. , Lu Hanbing , Yang Yihong , Ikemoto Satoshi
Published: May 2021

The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.
Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer
Authors: Shi Wengui , Zhang Gengyuan , Ma Zhijian , Li Lianshun , Liu Miaomiao , Qin Long , Yu Zeyuan , Zhao Lei , Liu Yang , Zhang Xue , Qin Junjie , Ye Huili , Jiang Xiangyan , Zhou Huinian , Sun Hui , Jiao Zuoyi
Published: May 2021

Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Released SHCBP1 responds to HER2 cascade by translocating into the nucleus following Ser273 phosphorylation, and then contributing to cell mitosis regulation through binding with PLK1 to promote the phosphorylation of the mitotic interactor MISP. Meanwhile, Shc1 is recruited to HER2 for MAPK or PI3K pathways activation. Also, clinical evidence shows that increased SHCBP1 prognosticates a poor response of patients to trastuzumab therapy. Theaflavine-3, 3’-digallate (TFBG) is identified as an inhibitor of the SHCBP1-PLK1 interaction, which is a potential trastuzumab sensitizing agent and, in combination with trastuzumab, is highly efficacious in suppressing HER2-positive gastric cancer growth. These findings suggest an aberrant mitotic HER2-SHCBP1-PLK1 axis underlies trastuzumab sensitivity and offer a new strategy to combat gastric cancer.
Rapid synchronized fabrication of vascularized thermosets and composites
Authors: Garg Mayank , Aw Jia En , Zhang Xiang , Centellas Polette J. , Dean Leon M. , Lloyd Evan M. , Robertson Ian D. , Liu Yiqiao , Yourdkhani Mostafa , Moore Jeffrey S. , Geubelle Philippe H. , Sottos Nancy R.
Published: May 2021

Bioinspired vascular networks transport heat and mass in hydrogels, microfluidic devices, self-healing and self-cooling structures, filters, and flow batteries. Lengthy, multistep fabrication processes involving solvents, external heat, and vacuum hinder large-scale application of vascular networks in structural materials. Here, we report the rapid (seconds to minutes), scalable, and synchronized fabrication of vascular thermosets and fiber-reinforced composites under ambient conditions. The exothermic frontal polymerization (FP) of a liquid or gelled resin facilitates coordinated depolymerization of an embedded sacrificial template to create host structures with high-fidelity interconnected microchannels. The chemical energy released during matrix polymerization eliminates the need for a sustained external heat source and greatly reduces external energy consumption for processing. Programming the rate of depolymerization of the sacrificial thermoplastic to match the kinetics of FP has the potential to significantly expedite the fabrication of vascular structures with extended lifetimes, microreactors, and imaging phantoms for understanding capillary flow in biological systems.
Electromechanical coupling mechanism for activation and inactivation of an HCN channel
Authors: Dai Gucan , Aman Teresa K. , DiMaio Frank , Zagotta William N.
Published: May 2021

Pacemaker hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels exhibit a reversed voltage-dependent gating, activating by membrane hyperpolarization instead of depolarization. Sea urchin HCN (spHCN) channels also undergo inactivation with hyperpolarization which occurs only in the absence of cyclic nucleotide. Here we applied transition metal ion FRET, patch-clamp fluorometry and Rosetta modeling to measure differences in the structural rearrangements between activation and inactivation of spHCN channels. We found that removing cAMP produced a largely rigid-body rotation of the C-linker relative to the transmembrane domain, bringing the A’ helix of the C-linker in close proximity to the voltage-sensing S4 helix. In addition, rotation of the C-linker was elicited by hyperpolarization in the absence but not the presence of cAMP. These results suggest that — in contrast to electromechanical coupling for channel activation — the A’ helix serves to couple the S4-helix movement for channel inactivation, which is likely a conserved mechanism for CNBD-family channels.
Context-specific action of macrolide antibiotics on the eukaryotic ribosome
Authors: Svetlov Maxim S. , Koller Timm O. , Meydan Sezen , Shankar Vaishnavi , Klepacki Dorota , Polacek Norbert , Guydosh Nicholas R. , Vázquez-Laslop Nora , Wilson Daniel N. , Mankin Alexander S.
Published: May 2021

Macrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of proteins. Because preventing translation of individual proteins could be beneficial for the treatment of human diseases, we asked whether macrolides, if bound to the eukaryotic ribosome, would retain their context- and protein-specific action. By introducing a single mutation in rRNA, we rendered yeast Saccharomyces cerevisiae cells sensitive to macrolides. Cryo-EM structural analysis showed that the macrolide telithromycin binds in the tunnel of the engineered eukaryotic ribosome. Genome-wide analysis of cellular translation and biochemical studies demonstrated that the drug inhibits eukaryotic translation by preferentially stalling ribosomes at distinct sequence motifs. Context-specific action markedly depends on the macrolide structure. Eliminating macrolide-arrest motifs from a protein renders its translation macrolide-tolerant. Our data illuminate the prospects of adapting macrolides for protein-selective translation inhibition in eukaryotic cells.
Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions
Authors: Zhang Jingjing , Yang Jin-Dong , Cheng Jin-Pei
Published: May 2021

Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively constructgem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. This metal-free hydrodefluorination features mild reaction conditions, good group compatibility, and almost quantitative yields for both product types. Stoichiometric experiments indicated a stepwise mechanism: hydridic addition to fluoroalkenes and subsequentβ-F elimination from hydrophosphination intermediates. Density functional theory calculations disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.
Spectroscopic evidence of superconductivity pairing at 83 K in single-layer FeSe/SrTiO3 films
Authors: Xu Yu , Rong Hongtao , Wang Qingyan , Wu Dingsong , Hu Yong , Cai Yongqing , Gao Qiang , Yan Hongtao , Li Cong , Yin Chaohui , Chen Hao , Huang Jianwei , Zhu Zhihai , Huang Yuan , Liu Guodong , Xu Zuyan , Zhao Lin , Zhou X. J.
Published: May 2021

Single-layer FeSe films grown on the SrTiO3 substrate (FeSe/STO) have attracted much attention because of their possible record-high superconducting critical temperature (Tc) and distinct electronic structures. However, it has been under debate on how high its Tc can really reach due to the inconsistency of the results from different measurements. Here we report spectroscopic evidence of superconductivity pairing at 83 K in single-layer FeSe/STO films. By preparing high-quality single-layer FeSe/STO films, we observe strong superconductivity-induced Bogoliubov back-bending bands that extend to rather high binding energy ~ 100 meV by high-resolution angle-resolved photoemission measurements. They provide a new definitive benchmark of superconductivity pairing that is directly observed up to 83 K. Moreover, we find that the pairing state can be further divided into two temperature regions. These results indicate that either Tc as high as 83 K is achievable, or there is a pseudogap formation from superconductivity fluctuation in single-layer FeSe/STO films.
The membrane-localized protein kinase MAP4K4/TOT3 regulates thermomorphogenesis
Authors: Vu Lam Dai , Xu Xiangyu , Zhu Tingting , Pan Lixia , van Zanten Martijn , de Jong Dorrit , Wang Yaowei , Vanremoortele Tim , Locke Anna M. , van de Cotte Brigitte , De Winne Nancy , Stes Elisabeth , Russinova Eugenia , De Jaeger Geert , Van Damme Daniël , Uauy Cristobal , Gevaert Kris , De Smet Ive
Published: May 2021

Plants respond to mild warm temperature conditions by increased elongation growth of organs to enhance cooling capacity, in a process called thermomorphogenesis. To this date, the regulation of thermomorphogenesis has been exclusively shown to intersect with light signalling pathways. To identify regulators of thermomorphogenesis that are conserved in flowering plants, we map changes in protein phosphorylation in both dicots and monocots exposed to warm temperature. We identify MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE KINASE4 (MAP4K4)/TARGET OF TEMPERATURE3 (TOT3) as a regulator of thermomorphogenesis that impinges on brassinosteroid signalling inArabidopsis thaliana. In addition, we show that TOT3 plays a role in thermal response in wheat, a monocot crop. Altogether, the conserved thermal regulation by TOT3 expands our knowledge of thermomorphogenesis beyond the well-studied pathways and can contribute to ensuring food security under a changing climate.
Multifunctional antiferromagnetic materials with giant piezomagnetism and noncollinear spin current
Authors: Ma Hai-Yang , Hu Mengli , Li Nana , Liu Jianpeng , Yao Wang , Jia Jin-Feng , Liu Junwei
Published: May 2021

We propose a new type of spin-valley locking (SVL), named C-paired SVL, in antiferromagnetic systems, which directly connects the spin/valley space with the real space, and hence enables both static and dynamical controls of spin and valley to realize a multifunctional antiferromagnetic material. The new emergent quantum degree of freedom in the C-paired SVL is comprised of spin-polarized valleys related by a crystal symmetry instead of the time-reversal symmetry. Thus, both spin and valley can be accessed by simply breaking the corresponding crystal symmetry. Typically, one can use a strain field to induce a large net valley polarization/magnetization and use a charge current to generate a large noncollinear spin current. We predict the realization of the C-paired SVL in monolayer V2Se2O, which indeed exhibits giant piezomagnetism and can generate a large transverse spin current. Our findings provide unprecedented opportunities to integrate various controls of spin and valley with nonvolatile information storage in a single material, which is highly desirable for versatile fundamental research and device applications.
Hierarchical progressive learning of cell identities in single-cell data
Authors: Michielsen Lieke , Reinders Marcel J. T. , Mahfouz Ahmed
Published: May 2021

Supervised methods are increasingly used to identify cell populations in single-cell data. Yet, current methods are limited in their ability to learn from multiple datasets simultaneously, are hampered by the annotation of datasets at different resolutions, and do not preserve annotations when retrained on new datasets. The latter point is especially important as researchers cannot rely on downstream analysis performed using earlier versions of the dataset. Here, we present scHPL, a hierarchical progressive learning method which allows continuous learning from single-cell data by leveraging the different resolutions of annotations across multiple datasets to learn and continuously update a classification tree. We evaluate the classification and tree learning performance using simulated as well as real datasets and show that scHPL can successfully learn known cellular hierarchies from multiple datasets while preserving the original annotations. scHPL is available at https://github.com/lcmmichielsen/scHPL.
STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses
Authors: Scott Ori , Lindsay Kyle , Erwood Steven , Mollica Antonio , Roifman Chaim M. , Cohn Ronald D. , Ivakine Evgueni A.
Published: May 2021

Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) is an autosomal dominant immune disorder marked by wide infectious predisposition, autoimmunity, vascular disease, and malignancy. Its molecular hallmark, elevated phospho-STAT1 (pSTAT1) following interferon (IFN) stimulation, is seen consistently in all patients and may not fully account for the broad phenotypic spectrum associated with this disorder. While over 100 mutations have been implicated in STAT1 GOF, genotype–phenotype correlation remains limited, and current overexpression models may be of limited use in gene expression studies. We generated heterozygous mutants in diploid HAP1 cells using CRISPR/Cas9 base-editing, targeting the endogenous STAT1 gene. Our models recapitulated the molecular phenotype of elevated pSTAT1, and were used to characterize the expression of five IFN-stimulated genes under a number of conditions. At baseline, transcriptional polarization was evident among mutants compared with wild type, and this was maintained following prolonged serum starvation. This suggests a possible role for unphosphorylated STAT1 in the pathogenesis of STAT1 GOF. Following stimulation with IFNα or IFNγ, differential patterns of gene expression emerged among mutants, including both gain and loss of transcriptional function. This work highlights the importance of modeling heterozygous conditions, and in particular transcription factor-related disorders, in a manner which accurately reflects patient genotype and molecular signature. Furthermore, we propose a complex and multifactorial transcriptional profile associated with various STAT1 mutations, adding to global efforts in establishing STAT1 GOF genotype–phenotype correlation and enhancing our understanding of disease pathogenesis.
Negative thermal expansion in YbMn2Ge2 induced by the dual effect of magnetism and valence transition
Authors: Qiao Yongqiang , Song Yuzhu , Sanson Andrea , Fan Longlong , Sun Qiang , Hu Shuxian , He Lunhua , Zhang Hongjie , Xing Xianran , Chen Jun
Published: May 2021

Negative thermal expansion (NTE) is an intriguing property, which is generally triggered by a single NTE mechanism. In this work, an enhanced NTE (αv = −32.9 × 10−6 K−1, ΔT = 175 K) is achieved in YbMn2Ge2 intermetallic compound to be caused by a dual effect of magnetism and valence transition. In YbMn2Ge2, the Mn sublattice that forms the antiferromagnetic structure induces the magnetovolume effect, which contributes to the NTE below the Néel temperature (525 K). Concomitantly, the valence state of Yb increases from 2.40 to 2.82 in the temperature range of 300–700 K, which simultaneously causes the contraction of the unit cell volume due to smaller volume of Yb3+ than that of Yb2+. As a result, such combined effect gives rise to an enhanced NTE. The present study not only sheds light on the peculiar NTE mechanism of YbMn2Ge2, but also indicates the dual effect as a possible promising method to produce enhanced NTE materials.
Natural language processing methods are sensitive to sub-clinical linguistic differences in schizophrenia spectrum disorders
Authors: Tang Sunny X. , Kriz Reno , Cho Sunghye , Park Suh Jung , Harowitz Jenna , Gur Raquel E. , Bhati Mahendra T. , Wolf Daniel H. , Sedoc João , Liberman Mark Y.
Published: May 2021

Computerized natural language processing (NLP) allows for objective and sensitive detection of speech disturbance, a hallmark of schizophrenia spectrum disorders (SSD). We explored several methods for characterizing speech changes in SSD (n = 20) compared to healthy control (HC) participants (n = 11) and approached linguistic phenotyping on three levels: individual words, parts-of-speech (POS), and sentence-level coherence. NLP features were compared with a clinical gold standard, the Scale for the Assessment of Thought, Language and Communication (TLC). We utilized Bidirectional Encoder Representations from Transformers (BERT), a state-of-the-art embedding algorithm incorporating bidirectional context. Through the POS approach, we found that SSD used more pronouns but fewer adverbs, adjectives, and determiners (e.g., “the,” “a,”). Analysis of individual word usage was notable for more frequent use of first-person singular pronouns among individuals with SSD and first-person plural pronouns among HC. There was a striking increase in incomplete words among SSD. Sentence-level analysis using BERT reflected increased tangentiality among SSD with greater sentence embedding distances. The SSD sample had low speech disturbance on average and there was no difference in group means for TLC scores. However, NLP measures of language disturbance appear to be sensitive to these subclinical differences and showed greater ability to discriminate between HC and SSD than a model based on clinical ratings alone. These intriguing exploratory results from a small sample prompt further inquiry into NLP methods for characterizing language disturbance in SSD and suggest that NLP measures may yield clinically relevant and informative biomarkers.
Comprehensive dataset of shotgun metagenomes from oxygen stratified freshwater lakes and ponds
Authors: Buck Moritz , Garcia Sarahi L. , Fernandez Leyden , Martin Gaëtan , Martinez-Rodriguez Gustavo A. , Saarenheimo Jatta , Zopfi Jakob , Bertilsson Stefan , Peura Sari
Published: May 2021

Stratified lakes and ponds featuring steep oxygen gradients are significant net sources of greenhouse gases and hotspots in the carbon cycle. Despite their significant biogeochemical roles, the microbial communities, especially in the oxygen depleted compartments, are poorly known. Here, we present a comprehensive dataset including 267 shotgun metagenomes from 41 stratified lakes and ponds mainly located in the boreal and subarctic regions, but also including one tropical reservoir and one temperate lake. For most lakes and ponds, the data includes a vertical sample set spanning from the oxic surface to the anoxic bottom layer. The majority of the samples were collected during the open water period, but also a total of 29 samples were collected from under the ice. In addition to the metagenomic sequences, the dataset includes environmental variables for the samples, such as oxygen, nutrient and organic carbon concentrations. The dataset is ideal for further exploring the microbial taxonomic and functional diversity in freshwater environments and potential climate change impacts on the functioning of these ecosystems.
A biomechanical paradox in fish: swimming and suction feeding produce orthogonal strain gradients in the axial musculature
Authors: Jimenez Yordano E. , Marsh Richard L. , Brainerd Elizabeth L.
Published: May 2021

The axial musculature of fishes has historically been characterized as the powerhouse for explosive swimming behaviors. However, recent studies show that some fish also use their ‘swimming’ muscles to generate over 90% of the power for suction feeding. Can the axial musculature achieve high power output for these two mechanically distinct behaviors? Muscle power output is enhanced when all of the fibers within a muscle shorten at optimal velocity. Yet, axial locomotion produces a mediolateral gradient of muscle strain that should force some fibers to shorten too slowly and others too fast. This mechanical problem prompted research into the gearing of fish axial muscle and led to the discovery of helical fiber orientations that homogenize fiber velocities during swimming, but does such a strain gradient also exist and pose a problem for suction feeding? We measured muscle strain in bluegill sunfish, Lepomis macrochirus, and found that suction feeding produces a gradient of longitudinal strain that, unlike the mediolateral gradient for locomotion, occurs along the dorsoventral axis. A dorsoventral strain gradient within a muscle with fiber architecture shown to counteract a mediolateral gradient suggests that bluegill sunfish should not be able to generate high power outputs from the axial muscle during suction feeding—yet prior work shows that they do, up to 438 W kg−1. Solving this biomechanical paradox may be critical to understanding how many fishes have co-opted ‘swimming’ muscles into a suction feeding powerhouse.
Room-temperature-superconducting Tc driven by electron correlation
Authors: Kim Hyun-Tak
Published: May 2021

Room-temperature-superconducting Tc measured by high pressure in hydrides can be theoretically explained by a Brinkman–Rice (BR)–Bardeen–Cooper–Schrieffer (BCS) Tc combining both the generalized BCS Tc and the diverging effective mass, m*/m = 1/(1 − (U/Uc)2), with the on-site Coulomb interaction U in the BR picture. A transition from U in a correlated metal of the normal state to Uc in the superconducting state can lead to superconductivity, which can be caused by volume contraction induced by high pressure or low temperature.
Genomic investigation of a dengue virus outbreak in Thiès, Senegal, in 2018
Authors: Gaye Amy , Ndiaye Tolla , Sy Mouhamad , Deme Awa B. , Thiaw Alphonse B. , Sene Aita , Ndiaye Cheikh , Diedhiou Younouss , Mbaye Amadou M. , Ndiaye Ibrahima , Tomkins-Tinch Christopher , Gomis Jules F. , Badiane Aida S. , MacInnis Bronwyn , Park Daniel J. , Ndiaye Mouhamadou , Sy Ngayo , Sabeti Pardis C. , Siddle Katherine J. , Ndiaye Daouda
Published: May 2021

Dengue virus is a major and rapidly growing public health concern in tropic and subtropic regions across the globe. In late 2018, Senegal experienced its largest dengue virus outbreak to date, covering several regions. However, little is known about the genetic diversity of dengue virus (DENV) in Senegal. Here we report complete viral genomes from 17 previously undetected DENV cases from the city of Thiès. In total we identified 19 cases of DENV in a cohort of 198 individuals with fever collected in October and November 2018. We detected 3 co-circulating serotypes; DENV 3 was the most frequent accounting for 11/17 sequences (65%), 4 (23%) were DENV2 and 2 (12%) were DENV1. Sequences were most similar to recent sequences from West Africa, suggesting ongoing local circulation of viral populations; however, detailed inference is limited by the scarcity of available genomic data. We did not find clear associations with reported clinical signs or symptoms, highlighting the importance of testing for diagnosing febrile diseases. Overall, these findings expand the known range of DENV in Senegal, and underscore the need for better genomic characterization of DENV in West Africa.
HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1
Authors: Fujino Shiki , Miyoshi Norikatsu , Ito Aya , Yasui Masayoshi , Matsuda Chu , Ohue Masayuki , Uemura Mamoru , Mizushima Tsunekazu , Doki Yuichiro , Eguchi Hidetoshi
Published: May 2021

POU5F1-expressing cells can self-renew and differentiate, contributing to metastasis formation in colorectal cancer (CRC), but it plays an important role in normal pluripotent stem cells. Here, we identified the CRC-specific gene, HNF1A, which is the downstream of POU5F1. HNF1A associates with fatty acid and glucose metabolism, and CRC cells highly expressed it. In 198 CRC patients, high HNF1A expression was an independent predictor of disease-free (P = 0.031) and overall (P = 0.007) survival. HNF1A-knockdown showed significantly reduced cell growth, increased apoptosis, and improved anticancer drug sensitivity. We revealed that HNF1A regulated controlled GLUT1 expression via HIF1A and multidrug resistance protein function to suppress SRI. HNF1A expression was elevated in persister cells after exposure to anticancer drugs, and anticancer drug sensitivity was also improved in persister cells via the inhibition of HNF1A. In conclusion, HNF1A expression can reflect resistance to anticancer drug treatment, and its suppression improves anticancer drug sensitivity as a new therapeutic target.
Dementia epidemiology in Hungary based on data from neurological and psychiatric specialty services
Authors: Balázs Nóra , Ajtay András , Oberfrank Ferenc , Bereczki Dániel , Kovács Tibor
Published: May 2021

Hungary has a single-payer health insurance system covering 10 million inhabitants. All medical reports of the in- and outpatient specialist services were collected in the NEUROHUN database. We used ICD-10 codes of Alzheimer’s disease (AD), vascular dementia (VaD), miscellaneous dementia group and mild cognitive impairment (MCI) for the inclusion of the patients. Incidence, prevalence and survival of different dementias and MCI were calculated and analyzed depending on the diagnoses given by neurological or psychiatric services or both. Between 2011 and 2016, the mean crude incidence of all dementias was 242/100,000/year, whereas the age standardized incidence was 287/100,000/year. Crude and age standardized mean prevalence rates were 570/100,000 and 649/100,000, respectively. There were significantly more VaD diagnoses than AD, the VaD:AD ratio was 2.54:1, being the highest in patients with psychiatric diagnoses only (4.85:1) and the lowest in patients with only neurological diagnoses (1.32:1). The median survival after the first diagnosis was 3.01 years regarding all dementia cases. Compared to international estimates, the prevalence of dementia and MCI is considerably lower in Hungary and the VaD:AD ratio is reversed.
Chorioamnionitis induces hepatic inflammation and time-dependent changes of the enterohepatic circulation in the ovine fetus
Authors: Heymans Cathelijne , den Dulk Marcel , Lenaerts Kaatje , Heij Lara R. , de Lange Ilse H. , Hadfoune Mhamed , van Heugten Chantal , Kramer Boris W. , Jobe Alan H. , Saito Masatoshi , Kemp Matthew W. , Wolfs Tim G. A. M. , van Gemert Wim G.
Published: May 2021

Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h – 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.
Uniportal video-assisted thoracic surgery for major lung resection is associated with less immunochemokine disturbances than multiportal approach
Authors: Yu Peter S. Y. , Chan Kin Wai , Lau Rainbow W. H. , Wan Innes Y. P. , Chen George G. , Ng Calvin S. H.
Published: May 2021

Multiportal video-assisted thoracic surgery (VATS) for major lung resection causes less immunochemokine production compared to thoracotomy. Whether uniportal VATS is similarly associated with lower early postoperative circulating levels of immunochemokines compared to multiportal VATS have not been studied. Selected patients who received uniportal or multiportal VATS major lung resection were recruited. Blood samples were collected preoperatively and on postoperative days 1 and 3 for enzyme linked immunosorbent assay of serum levels of Tissue Inhibitor of Metalloproteinase (TIMP)-1, Insulin Growth Factor Binding Protein (IGFBP)-3, and Matrix Metalloproteinase (MMP)-9. A linear mixed-effects models were used to analyze the effects of uniportal VATS on the postoperative circulating chemokine levels. From March 2014 to April 2017, 68 consecutive patients consented for the prospective study and received major lung resection by either uniportal VATS (N = 29) or multiportal VATS (N = 39) were identified. Uniportal VATS major lung resection was associated with lower post-operative levels of TIMP-1 and MMP-9 compared to multiportal VATS after controlling for the effects of the corresponding baseline level and the time of follow-up measurement. No difference was observed for the level of IGFBP-3. Less immunochemokine disturbances was observed after uniportal VATS major lung resection compared to multiportal VATS.
Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration
Authors: Grewal Manjot Kaur , Chandra Shruti , Bird Alan , Jeffery Glen , Sivaprasad Sobha
Published: May 2021

To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.
Micro-mechanical performance evaluation of expansive soil biotreated with indigenous bacteria using MICP method
Authors: Tiwari Nitin , Satyam Neelima , Sharma Meghna
Published: May 2021

This study explored the effect of indigenous bacteria present in the soil to stabilized swelling behavior and improving the mechanical property of expansive soil. The objective of the research is to investigate the effectiveness of the biostimulation microbial induced calcite precipitation (MICP) for controlling the swelling-shrinkage behavior and improving shear strength of expansive soil. An attempt was made to develop an effective procedure to culture the indigenous bacteria for treating clays with varying plasticity and improve their engineering behavior. The detailed procedure has been investigated to effectively apply the MICP technique in clay soil, considering its low permeable nature. The applicability of biostimulation to clayey soils in minimizing their swelling potential and improving the strength is assessed. Both macroscale and microscale studies were conducted on untreated and biostimulated soils to observe changes in plasticity, strength, swelling, mineralogical, chemical characteristics. The present method has shown an effective alternative to improve the road pavement subgrade without affecting the eco-system of natural soil. The method investigated the effective way of providing the enrichment and cementation solution in clayey soil, which is the major concern in current literature. The study confirms that the calcite content has been increased with biostimulated MICP treatment up to 205% in the treated specimens and which future increased the unconfined compressive strength and split tensile strength. A reduction in the swelling pressure and swell strain is also observed. The results show that a cost-effect and eco-friendly method can be deployed for stabilizing the road pavement subgrades. The statistical assessment using multivariate analysis and hierarchical clustering dendrogram has been carried out to investigate the effect of the MICP treatment protocol on different soil and engineering parameters.
A primary study of breeding system of Ziziphus jujuba var. spinosa
Authors: Wang Feng , Sun Xiaohan , Dong Jibin , Cui Rong , Liu Xiao , Li Xiangxiang , Wang Hui , He Tongli , Zheng Peiming , Wang Renqing
Published: May 2021

Ziziphus jujuba var. spinosa has been used as a windbreak and for soil conservation and water retention. Previous studies focused on pharmacological effects and extraction of chemical components in this species, and very few explored the breeding system. The present study combined the analysis of floral morphology, behavior of flower visitors, and artificial pollination to reveal reproductive characteristics of the species. Its flowers are characterized by dichogamy, herkogamy, and stamen movement, which are evolutionary adaptations to its breeding system. There were more than 40 species of visiting insects, mainly Hymenoptera and Diptera, and the characteristics of dichogamous and herkogamous flower adapted to the visiting insects. The breeding system is outcrossing, partially self-compatible, and demand for pollinators. The fruit setting rate after natural pollination was 2%. Geitonogamy and xenogamy did not significantly increase the fruit setting rate, indicating that the low fruit setting rate was not due to pollen limitation by likely caused by resource limitation or fruit consumption. The fruit setting rate of zero in emasculated and in naturally and hand self-pollinated individuals suggested the absence of apomixis and spontaneous self-pollination. The above results can be utilized in studies on evolution and cultivation of Z. jujuba var. spinosa.
Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
Authors: Shrivastava Vipul , Lee Megan , Lee Daniel , Pretorius Marle , Radford Bethany , Makkar Guneet , Huang Carol
Published: May 2021

Pancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr+/−), we found Prlr signaling is important for this adaptation. However, since Prlr is expressed in tissues outside of islets as well as within islets and prolactin signaling affects β-cell development, to understand β-cell-specific effect of prolactin signaling in pregnancy, we generated a transgenic mouse with an inducible conditional deletion of Prlr from β-cells. Here, we found that β-cell-specific Prlr reduction in adult mice led to elevated blood glucose, lowed β-cell mass and blunted in vivo glucose-stimulated insulin secretion during pregnancy. When we compared gene expression profile of islets from transgenic mice with global (Prlr+/−) versus β-cell-specific Prlr reduction (βPrlR+/−), we found 95 differentially expressed gene, most of them down regulated in the Prlr+/−mice in comparison to the βPrlR+/−mice, and many of these genes regulate apoptosis, synaptic vesicle function and neuronal development. Importantly, we found that islets from pregnant Prlr+/−mice are more vulnerable to glucolipotoxicity-induced apoptosis than islets from pregnant βPrlR+/−mice. These observations suggest that down regulation of prolactin action during pregnancy in non-β-cells secondarily and negatively affect β-cell gene expression, and increased β-cell susceptibility to external insults.
Regional height growth models for Scots pine in Poland
Authors: Socha Jarosław , Tymińska-Czabańska Luiza , Bronisz Karol , Zięba Stanisław , Hawryło Paweł
Published: May 2021

Site productivity remains a fundamental concern in forestry as a significant driver of resource availability for tree growth. The site index (SI) reflects the overall impact of all environmental factors that determine tree height growth and is the most commonly used indirect proxy for forest site productivity estimated using stand age and height. The SI concept challenges are local variations in climate, soil, and genotype-environmental interactions that lead to variable height growth patterns among ecoregions and cause inappropriate estimation of site productivity. Developing regional models allow us to determine forest growth and SI more appropriately. This study aimed to develop height growth models for the Scots pine in Poland, considering the natural forest region effect. For height growth modelling, we used the growth trajectory data of 855 sample trees, representing the Scots pine entire range of geographic locations and site conditions in Poland. We compared the development of regional height growth models using nonlinear-fixed-effects (NFE) and nonlinear-mixed-effects (NME) modelling approaches. Our results indicate a slightly better fit to the data of the model built using NFE approach. The results showed significant differences between Scots pine growth in natural forest regions I, II, and III located in northern Poland and natural forest regions IV, V, and VI in southern Poland. We compared the development of regional height growth models using NFE and NME modelling approaches. Our results indicate a slightly better fit to the data of the model built using the NFE approach. The developed models show differences in height growth patterns of Scots pines in Poland and revealed that acknowledgement of region as the independent variable could improve the growth prediction and quality of the SI estimation. Differences in climate and soil conditions that distinguish natural forest regions affect Scots pine height growth patterns. Therefore, extending this research to models that directly describe height growth interactions with site variables, such as climate, soil properties, and topography, can provide valuable forest management information.
Fungus-mediated green synthesis of nano-silver using Aspergillus sydowii and its antifungal/antiproliferative activities
Authors: Wang Dongyang , Xue Baiji , Wang Lin , Zhang Yidi , Liu Lijun , Zhou Yanmin
Published: May 2021

Due to the increasing demand for eco-friendly, cost-effective and safe technologies, biosynthetic metal nanoparticles have attracted worldwide attention. In this study, silver nanoparticles (AgNPs) were extracellularly biosynthesized using the culture supernatants ofAspergillus sydowii. During synthesis, color change was preliminarily judge of the generation of AgNPs, and the UV absorption peak at 420 nm further confirms the production of AgNPs. Transmission electron microscopy and X-ray diffraction were also used to identify the AgNPs. The results shows that AgNPs has crystalline cubic feature and is a polydisperse spherical particle with size between 1 and 24 nm. Three main synthesis factors (temperature, pH and substrate concentration) were optimized, the best synthesis conditions were as follows 50 °C, 8.0 and 1.5 mM. In the biological application of AgNPs, it shows effective antifungal activity against many clinical pathogenic fungi and antiproliferative activity to HeLa cells and MCF-7 cells in vitro. Our research finds a new path to biosynthesis of AgNPs in an eco-friendly manner, and bring opportunity for biomedical applications in clinic.
Highly stable two-dimensional metal-carbon monolayer with interpenetrating honeycomb structures
Authors: Li Shulong , Yam Kah-Meng , Guo Na , Zhao Yong , Zhang Chun
Published: May 2021

With the ongoing effort in proposing and realizing functional two-dimensional (2D) materials, we predict by first-principles calculations a family of 2D metal-carbon (M–C) crystals consisting of M–C trigonal lattice interpenetrated with the metal buckled honeycomb structure. We suggest by simulations that the 2D M–C crystals can be readily fabricated by a self-organizing lattice reconstruction process after placing metal atoms on hollow sites of γ-graphyne. In total, we found 12 members of the family and they exhibit a variety of electronic and magnetic properties. In this work, we highlight and focus on the Fe member of the family, 2D-Fe2C12. Each Fe in 2D-Fe2C12 has a magnetic moment of 1 μB due to the spin splitting of Fe E1 bands at Fermi surface, resulting in half metallicity and high catalytic activity with unusually high-density single-atom Fe active sites. Ab initio molecular dynamics simulations revealed that the 2D-Fe2C12 retains its structural integrity up to 700 K of simulated short duration annealing. We expect these results to stimulate experimental research for the 2D M–C crystals we proposed.
Differential effects of the blood pressure state on pulse rate variability and heart rate variability in critically ill patients
Authors: Mejía-Mejía Elisa , May James M. , Elgendi Mohamed , Kyriacou Panayiotis A.
Published: May 2021

Heart rate variability (HRV) utilizes the electrocardiogram (ECG) and has been widely studied as a non-invasive indicator of cardiac autonomic activity. Pulse rate variability (PRV) utilizes photoplethysmography (PPG) and recently has been used as a surrogate for HRV. Several studies have found that PRV is not entirely valid as an estimation of HRV and that several physiological factors, including the pulse transit time (PTT) and blood pressure (BP) changes, may affect PRV differently than HRV. This study aimed to assess the relationship between PRV and HRV under different BP states: hypotension, normotension, and hypertension. Using the MIMIC III database, 5 min segments of PPG and ECG signals were used to extract PRV and HRV, respectively. Several time-domain, frequency-domain, and nonlinear indices were obtained from these signals. Bland–Altman analysis, correlation analysis, and Friedman rank sum tests were used to compare HRV and PRV in each state, and PRV and HRV indices were compared among BP states using Kruskal–Wallis tests. The findings indicated that there were differences between PRV and HRV, especially in short-term and nonlinear indices, and although PRV and HRV were altered in a similar manner when there was a change in BP, PRV seemed to be more sensitive to these changes.
Sperm modulate uterine immune parameters relevant to embryo implantation and reproductive success in mice
Authors: Schjenken John E. , Sharkey David J. , Green Ella S. , Chan Hon Yeung , Matias Ricky A. , Moldenhauer Lachlan M. , Robertson Sarah A.
Published: May 2021

Seminal fluid factors modulate the female immune response at conception to facilitate embryo implantation and reproductive success. Whether sperm affect this response has not been clear. We evaluated global gene expression by microarray in the mouse uterus after mating with intact or vasectomized males. Intact males induced greater changes in gene transcription, prominently affecting pro-inflammatory cytokine and immune regulatory genes, with TLR4 signaling identified as a top-ranked upstream driver. Recruitment of neutrophils and expansion of peripheral regulatory T cells were elevated by seminal fluid of intact males. In vitro, epididymal sperm induced IL6, CXCL2, and CSF3 in uterine epithelial cells of wild-type, but notTlr4null females. Collectively these experiments show that sperm assist in promoting female immune tolerance by eliciting uterine cytokine expression through TLR4-dependent signaling. The findings indicate a biological role for sperm beyond oocyte fertilization, in modulating immune mechanisms involved in female control of reproductive investment.
Genome-resolved metagenomics suggests a mutualistic relationship between Mycoplasma and salmonid hosts
Authors: Rasmussen Jacob A. , Villumsen Kasper R. , Duchêne David A. , Puetz Lara C. , Delmont Tom O. , Sveier Harald , Jørgensen Louise von Gersdorff , Præbel Kim , Martin Michael D. , Bojesen Anders M. , Gilbert M. Thomas P. , Kristiansen Karsten , Limborg Morten T.
Published: May 2021

Salmonids are important sources of protein for a large proportion of the human population.Mycoplasmaspecies are a major constituent of the gut microbiota of salmonids, often representing the majority of microbiota. Despite the frequent reported dominance of salmonid-relatedMycoplasmaspecies, little is known about the phylogenomic placement, functions and potential evolutionary relationships with their salmonid hosts. In this study, we utilise 2.9 billion metagenomic reads generated from 12 samples from three different salmonid host species to I) characterise and curate the first metagenome-assembled genomes (MAGs) ofMycoplasmadominating the intestines of three different salmonid species, II) establish the phylogeny of these salmonid candidateMycoplasmaspecies, III) perform a comprehensive pangenomic analysis ofMycoplasma, IV) decipher the putative functionalities of the salmonid MAGs and reveal specific functions expected to benefit the host. Our data provide a basis for future studies examining the composition and function of the salmonid microbiota.
Visible light-induced mono-bromination of arenes with BrCCl3
Authors: Fan Jiali , Wei Qiancheng , Zhu Ershu , Gao Jing , Cheng Xiamin , Lu Yongna , Loh Teck-Peng
Published: May 2021

We reported a highly efficient and regioselective photocatalytic bromination of electron-rich arenes and heteroarenes using commercially available BrCCl3 as a “Br” source.
Immune evasion of SARS-CoV-2 variants of concern is driven by low affinity to neutralizing antibodies
Authors: Ferraz Matheus V. F. , Moreira Emerson G. , Coêlho Danilo F. , Wallau Gabriel L. , Lins Roberto D.
Published: May 2021

Electrostatics and loss of chemical interactions play an important role in immune evasion of SARS-CoV-2 variants of concern (VOCs). The low affinity between VOC RBDs and previously elicited neutralizing antibodies is key.
Electronic, magnetic, vibrational, and X-ray spectroscopy of inverse full-Heusler Fe2IrSi alloy
Authors: Lalrinkima  , Ekuma C. E. , Chibueze T. C. , Fomin L. A. , Malikov I. V. , Zadeng L. , Rai D. P.
Published: May 2021

The electronic, magnetic, structural, vibrational, and X-ray absorption spectroscopy of inverse full-Heusler Fe2IrSi alloy has been studied from density functional theory (DFT). The XA-phase with FM-configuration is the most stable one, structurally and thermodynamically.
Understanding the role of hydrophobic patches in protein disaggregation
Authors: Kumar Avishek , Singh Nitin Kumar , Ghosh Deepshikha , Radhakrishna Mithun
Published: May 2021

Protein folding is a very complex process and, so far, the mechanism of folding still intrigues the research community.