bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of tamoxifen-induced Cre activity and its effect on immune cell populations
Authors: Donocoff Rachel S. , Teteloshvili Nato , Chung Hyunsoo , Shoulson Rivka , Creusot Remi J. 
Published: September 2020

AbstractTamoxifen (TAM) inducible Cre recombinase system is an essential tool to study gene function when early ablation or overexpression can cause developmental defects or embryonic lethality. However, there remains a lack of consensus on the optimal route and dosage of TAM administration in vivo. Here, we assessed dosage and delivery of TAM for activation of Cre in immune cell subsets assessed longitudinally and spatially using transgenic mice with ubiquitously expressed Cre/ER and the Cre-inducible fluorescent reporter YFP. After comparing two TAM delivery methods (intraperitoneal versus oral gavage) and different doses, we found that 3 mg of TAM administered orally for five consecutive days provides maximal reporter induction with minimal adverse effects in vivo. Serum levels of TAM peaked 1 week after initiating treatment then slowly decreased, regardless of dosing and delivery methods. TAM concentration in specific tissues (liver, spleen, lymph nodes, and thymus) was also dependent on delivery method and dose. Cre induction was highest in myeloid cells and B cells and substantially lower in T cells, and double-positive thymocytes had a notably higher response to TAM. In addition to establishing optimal dose and administration of TAM, our study reveals a disparate activity of Cre in different cell immune populations when using Cre/ER models.
Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses
Authors: de Andrade Danilo Giorgi Abranches , Basso Roberta Martins , Magro Angelo José , Laufer-Amorim Renée , Borges Alexandre Secorun , de Oliveira-Filho José Paes 
Published: September 2020

AbstractChondrodysplastic dwarfism in Miniature horses is an autosomal recessive disorder previously associated with four mutations (D1, D2, D3*, and D4) in the aggrecan (ACAN) gene. The aim of this study was to identify additional variants in the candidate ACAN gene associated with chondrodysplastic dwarfism in Miniature horses. Fifteen dwarf Miniature horses were found to possess only one of the dwarfism-causing variants, and two possessed none of the variants. The ACAN exons (EquCab3.0) of seven dwarf Miniature horses were sequenced. A missense SNP in coding exon 11 (g.95271115A > T, c.6465A > T—RefSeq XM_005602799.2), which resulted in the amino acid substitution p.Leu2155Phe (RefSeq XP_005602856.2), was initially associated with the dwarf phenotype. The variant was tested and found present in 14 dwarf foals as well as one parent of each, and both parents of a dwarf possessing two copies. Genetic testing of 347 phenotypically normal Miniature horses demonstrated that none had more than one of the dwarf alleles or c.6465A > T. However, a study of large breeds revealed the presence of c.6465A > T, which was present in homozygosis in two Mangalarga Marchador horses. We suggest that c.6465A > T as a marker of disequilibrium or complex interactions in the Miniature horse genome could contribute to the associated dwarfism.
Dynamics of human B and T cell adaptive immune responses to Kyasanur Forest disease virus infection
Authors: Devadiga Santhosha , McElroy Anita K. , Prabhu Suresha G. , Arunkumar Govindakarnavar 
Published: September 2020

AbstractKyasanur Forest disease (KFD) is a tick-borne, acute, febrile viral illness endemic in southern India. No major studies have been done to understand the adaptive immune response during KFDV infection in humans. In this study, KFDV-positive patients were prospectively enrolled, and repeated peripheral blood collections were performed. Clinical and virologic characterization of these samples is reported along with phenotypic analysis of cellular immunity and quantitation of humoral immunity. We noted robust T and B cell responses, particularly of CD8 T cells, during KFDV infection in most of the patients. Virus clearance from the blood coincided with peak CD8 T cell activation and the appearance of KFDV-specific IgG. Increased frequency of plasmablasts and very few activated B cells were observed in the acute phase of KFD infection. Notably, only humoral immunity and activated B cell frequency in the acute phase correlated with prior KFDV vaccination, and only with 2 or more doses. This novel work has implications in KFD vaccine research as well as in understanding the pathogenesis.
Hurricane-induced power outage risk under climate change is primarily driven by the uncertainty in projections of future hurricane frequency
Authors: Alemazkoor Negin , Rachunok Benjamin , Chavas Daniel R , Staid Andrea , Louhghalam Arghavan , Nateghi Roshanak , Tootkaboni Mazdak 
Published: September 2020

AbstractNine in ten major outages in the US have been caused by hurricanes. Long-term outage risk is a function of climate change-triggered shifts in hurricane frequency and intensity; yet projections of both remain highly uncertain. However, outage risk models do not account for the epistemic uncertainties in physics-based hurricane projections under climate change, largely due to the extreme computational complexity. Instead they use simple probabilistic assumptions to model such uncertainties. Here, we propose a transparent and efficient framework to, for the first time, bridge the physics-based hurricane projections and intricate outage risk models. We find that uncertainty in projections of the frequency of weaker storms explains over 95% of the uncertainty in outage projections; thus, reducing this uncertainty will greatly improve outage risk management. We also show that the expected annual fraction of affected customers exhibits large variances, warranting the adoption of robust resilience investment strategies and climate-informed regulatory frameworks.
An inherent instability study using ab initio computational methods and experimental validation of Pb(SCN)2 based perovskites for solar cell applications
Authors: Dutta Jayita , Chennamkulam Ajith Mithun , Dutta Soumya , R. Kadhane Umesh , Kochupurackal B Jinesh , Rai Beena 
Published: September 2020

AbstractPerovskite materials with ABX3chemistries are promising candidates for photovoltaic applications, owing to their suitable optoelectronic properties. However, they are highly hydrophilic and unstable in nature, limiting the commercialization of perovskite photovoltaics. Mixed halide ion-doped perovskites are reported to be more stable compared to simple ABX3chemistries. This paper describes ab initio modeling, synthesis, and characterization of thiocyanate doped lead iodide CH3NH3PbI(3−x)(SCN)xperovskites. Several perovskite chemistries with an increasing concentration of (SCN)−at x = 0, 0.25, 0.49, 1.0, 1.45 were evaluated. Subsequently, ‘n-i-p’ and ‘p-i-n’ perovskite solar device architectures, corresponding to x = 0, 0.25, 0.49, 1.0 thiocyanate doped lead halide perovskite chemistry were fabricated. The study shows that among all the devices fabricated for different compositions of perovskites, p-i-n perovskite solar cell fabricated using CH3NH3PbI(3−x)(SCN)xperovskite at x = 1.0 exhibited the highest stability and device efficiency was retained until 450 h. Finally, a solar panel was fabricated and its stability was monitored.
Nociceptive mechanisms driving pain in a post-traumatic osteoarthritis mouse model
Authors: Alves C. J. , Couto M. , Sousa D. M. , Magalhães A. , Neto E. , Leitão L. , Conceição F. , Monteiro A. C. , Ribeiro-da-Silva M. , Lamghari M. 
Published: September 2020

AbstractIn osteoarthritis (OA), pain is the dominant clinical symptom, yet the therapeutic approaches remain inadequate. The knowledge of the nociceptive mechanisms in OA, which will allow to develop effective therapies for OA pain, is of utmost need. In this study, we investigated the nociceptive mechanisms involved in post-traumatic OA pain, using the destabilization of the medial meniscus (DMM) mouse model. Our results revealed the development of peripheral pain sensitization, reflected by augmented mechanical allodynia. Along with the development of pain behaviour, we observed an increase in the expression of calcitonin gene-related peptide (CGRP) in both the sensory nerve fibers of the periosteum and the dorsal root ganglia. Interestingly, we also observed that other nociceptive mechanisms commonly described in non-traumatic OA phenotypes, such as infiltration of the synovium by immune cells, neuropathic mechanisms and also central sensitization were not present. Overall, our results suggest that CGRP in the sensory nervous system is underlying the peripheral sensitization observed after traumatic knee injury in the DMM model, highlighting the CGRP as a putative therapeutic target to treat pain in post-traumatic OA. Moreover, our findings suggest that the nociceptive mechanisms involved in driving pain in post-traumatic OA are considerably different from those in non-traumatic OA.
Habitual sleep is associated with both source memory and hippocampal subfield volume during early childhood
Authors: Riggins Tracy , Spencer Rebecca M. C. 
Published: September 2020

AbstractPrevious research has established important developmental changes in sleep and memory during early childhood. These changes have been linked separately to brain development, yet few studies have explored their interrelations during this developmental period. The goal of this report was to explore these associations in 200 (100 female) typically developing 4- to 8-year-old children. We examined whether habitual sleep patterns (24-h sleep duration, nap status) were related to children’s performance on a source memory task and hippocampal subfield volumes. Results revealed that, across all participants, after controlling for age, habitual sleep duration was positively related to source memory performance. In addition, in younger (4–6 years, n = 67), but not older (6–8 years, n = 70) children, habitual sleep duration was related to hippocampal head subfield volume (CA2-4/DG). Moreover, within younger children, volume of hippocampal subfields varied as a function of nap status; children who were still napping (n = 28) had larger CA1 volumes in the body compared to children who had transitioned out of napping (n = 39). Together, these findings are consistent with the hypothesis that habitually napping children may have more immature cognitive networks, as indexed by hippocampal integrity. Furthermore, these results shed additional light on why sleep is important during early childhood, a period of substantial brain development.
Elevated acute phase proteins reflect peripheral inflammation and disease severity in patients with amyotrophic lateral sclerosis
Authors: Beers David R. , Zhao Weihua , Neal Daniel W. , Thonhoff Jason R. , Thome Aaron D. , Faridar Alireza , Wen Shixiang , Wang Jinghong , Appel Stanley H. 
Published: September 2020

AbstractAmyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem pro-inflammatory neuromuscular disorder compromising muscle function resulting in death. Neuroinflammation is known to accelerate disease progression and accentuate disease severity, but peripheral inflammatory processes are not well documented. Acute phase proteins (APPs), plasma proteins synthesized in the liver, are increased in response to inflammation. The objective of this study was to provide evidence for peripheral inflammation by examining levels of APPs, and their contribution to disease burden and progression rates. Levels of APPs, including soluble CD14 (sCD14), lipopolysaccharide binding protein (LBP), and C-reactive protein (CRP), were elevated in sera, and correlated positively with increased disease burden and faster progression. sCD14 was also elevated in patients’ CSF and urine. After a 3 year follow-up, 72% of the patients with sCD14 levels above the receiver operating characteristics cutoff were deceased whereas only 28% below the cutoff were deceased. Furthermore, disease onset sites were associated with disease progression rates and APP levels. These APPs were not elevated in sera of patients with Alzheimer’s Disease, frontotemporal dementia, or Parkinson’s Disease. These collective APPs accurately reflect disease burden, progression rates, and survival times, reinforcing the concept of ALS as a disorder with extensive systemic pro-inflammatory responses.
Tumor cells rely on the thiol oxidoreductase PDI for PERK signaling in order to survive ER stress
Authors: Kranz Philip , Sänger Christopher , Wolf Alexandra , Baumann Jennifer , Metzen Eric , Baumann Melanie , Göpelt Kirsten , Brockmeier Ulf 
Published: September 2020

AbstractUpon ER stress cells activate the unfolded protein response through PERK, IRE1 and ATF6. Remarkable effort has been made to delineate the downstream signaling of these three ER stress sensors after activation, but upstream regulation at the ER luminal site still remains mostly undefined. Here we report that the thiol oxidoreductase PDI is mandatory for activation of the PERK pathway in HEK293T as well as in human pancreatic, lung and colon cancer cells. Under ER stress, depletion of PDI selectively abrogated eIF2α phosphorylation, induction of ATF4, CHOP and even BiP. Furthermore, we could demonstrate that PDI prevented degradation of activated PERK by the 26S proteasome and therefore contributes to maintained PERK signaling. As a result of decreased PERK activity, PDI depleted cells showed an increased vulnerability to ER stress induced by chemicals or ionizing radiation in 2D as well as in 3D culture models. We conclude that PDI is an obligatory regulator of the PERK pathway with future therapy implications.
Nonlinear optical properties of arsenic telluride and its use in ultrafast fiber lasers
Authors: Lee Jinho , Jhon Young In , Lee Kyungtaek , Jhon Young Min , Lee Ju Han 
Published: September 2020

AbstractWe report the first investigation results of the nonlinear optical properties of As2Te3. More specifically, the nonlinear optical absorption properties of the prepared α-As2Te3 were investigated at wavelengths of 1.56 and 1.9 μm using the open-aperture (OA) Z-scan technique. Using the OA Z-scan technique, the nonlinear absorption coefficients (β) of α-As2Te3 were estimated in a range from (− 54.8 ± 3.4) × 104 cm/GW to (− 4.9 ± 0.4) × 104 cm/GW depending on the irradiance of the input beam at 1.56 μm, whereas the values did from (− 19.8 ± 0.8) × 104 cm/GW to (− 3.2 ± 0.1) × 104 cm/GW at 1.9 μm. In particular, the β value at 1.56 μm is an order of magnitude larger than the previously reported values of other group-15 sesquichalcogenides such as Bi2Se3, Bi2Te3, and Bi2TeSe2. Furthermore, this is the first time report on β value of a group-15 sesquichalcogenide at a 1.9-μm wavelength. The density functional theory (DFT) calculations of the electronic band structures of α-As2Te3 were also conducted to obtain a better understanding of their energy band structure. The DFT calculations indicated that α-As2Te3 possess sufficient optical absorption in a wide wavelength region, including 1.5 μm, 1.9 μm, and beyond (up to 3.7 μm). Using both the measured nonlinear absorption coefficients and the theoretically obtained refractive indices from the DFT calculations, the imaginary parts of the third-order optical susceptibilities (Im χ(3)) of As2Te3 were estimated and they were found to vary from (− 39 ± 2.4) × 10–19 m2/V2 to (− 3.5 ± 0.3) × 10–19 m2/V2 at 1.56 μm and (− 16.5 ± 0.7) × 10–19 m2/V2 to (− 2.7 ± 0.1) × 10–19 m2/V2 at 1.9 μm, respectively, depending on the irradiance of the input beam. Finally, the feasibility of using α-As2Te3 for SAs was investigated, and the prepared SAs were thus tested by incorporating them into an erbium (Er)-doped fiber cavity and a thulium–holmium (Tm–Ho) co-doped fiber cavity for both 1.5 and 1.9 μm operation.
Population genetic diversity in an Iraqi population and gene flow across the Arabian Peninsula
Authors: Lazim Hayder , Almohammed Eida Khalaf , Hadi Sibte , Smith Judith 
Published: September 2020

AbstractY-STRs have emerged as important forensic and population genetic markers for human identification and population differentiation studies. Therefore, population databases for these markers have been developed for almost all major populations around the world. The Iraqi population encompasses several ethnic groups that need to be genetically characterised and evaluated for possible substructures. Previous studies on the Iraqi population based on Y-STR markers were limited by a restricted number of markers. A larger database for Iraqi Arab population needed to be developed to help study and compare the population with other Middle Eastern populations. Twenty-three Y-STR loci included in the PowerPlex Y23 (Promega, Madison, WI, USA) were typed in 254 males from the Iraqi Arab population. Global and regional Y-STR analysis demonstrated regional genetic continuity among the populations of Iraq, the Arabian Peninsula and the Middle East. The Iraqi Arab haplotypes were used to allocate samples to their most likely haplogroups using Athey’s Haplogroup Predictor tool. Prediction indicated predominance (36.6%) of haplogroup J1 in Iraqi Arabs. The migration rate between other populations and the Iraqis was inferred using coalescence theory in the Migrate-n program. Y-STR data were used to test different out-of-Africa migration models as well as more recent migrations within the Arabian Peninsula. The migration models demonstrated that gene flow to Iraq began from East Africa, with the Levantine corridor the most probable passageway out of Africa. The data presented here will enrich our understanding of genetic diversity in the region and introduce a PowerPlex Y23 database to the forensic community.
SMRT- and Illumina-based RNA-seq analyses unveil the ginsinoside biosynthesis and transcriptomic complexity in Panax notoginseng
Authors: Zhang Dan , Li Wei , Chen Zhong-jian , Wei Fu-gang , Liu Yun-long , Gao Li-zhi 
Published: September 2020

AbstractPanax notoginseng is one of the most widely used traditional Chinese herbs with particularly valued roots. Triterpenoid saponins are mainly specialized secondary metabolites, which medically act as bioactive components. Knowledge of the ginsenoside biosynthesis in P. notoginseng, which is of great importance in the industrial biosynthesis and genetic breeding program, remains largely undetermined. Here we combined single molecular real time (SMRT) and Second-Generation Sequencing (SGS) technologies to generate a widespread transcriptome atlas of P. notoginseng. We mapped 2,383 full-length non-chimeric (FLNC) reads to adjacently annotated genes, corrected 1,925 mis-annotated genes and merged into 927 new genes. We identified 8,111 novel transcript isoforms that have improved the annotation of the current genome assembly, of which we found 2,664 novel lncRNAs. We characterized more alternative splicing (AS) events from SMRT reads (20,015 AS in 6,324 genes) than Illumina reads (18,498 AS in 9,550 genes), which contained a number of AS events associated with the ginsenoside biosynthesis. The comprehensive transcriptome landscape reveals that the ginsenoside biosynthesis predominantly occurs in flowers compared to leaves and roots, substantiated by levels of gene expression, which is supported by tissue-specific abundance of isoforms in flowers compared to roots and rhizomes. Comparative metabolic analyses further show that a total of 17 characteristic ginsenosides increasingly accumulated, and roots contained the most ginsenosides with variable contents, which are extraordinarily abundant in roots of the three-year old plants. We observed that roots were rich in protopanaxatriol- and protopanaxadiol-type saponins, whereas protopanaxadiol-type saponins predominated in aerial parts (leaves, stems and flowers). The obtained results will greatly enhance our understanding about the ginsenoside biosynthetic machinery in the genus Panax.
Hepatitis C virus enhances Rubicon expression, leading to autophagy inhibition and intracellular innate immune activation
Authors: Shiode Yuto , Hikita Hayato , Tanaka Satoshi , Shirai Kumiko , Doi Akira , Sakane Sadatsugu , Kai Yugo , Nakabori Tasuku , Yamada Ryoko , Kodama Takahiro , Narumi Ryohei , Sakamori Ryotaro , Eguchi Hidetoshi , Tomonaga Takeshi , Tatsumi Tomohide , Takehara Tetsuo 
Published: September 2020

AbstractAutophagy, a degradation system, works to maintain cellular homeostasis. However, as the impact of Hepatitis C virus (HCV) infection on hepatocyte autophagy and its effect on HCV replication remain unclear, we examined them. HCV infection suppressed late-stage autophagy and increased Rubicon. siRNA-mediated knockdown of Rubicon promoted autophagy in HCV-infected cells. In Huh-7 cells harbouring the HCV replicon, Rubicon knockdown downregulated the expression of type 1 interferon (IFN)-related genes and upregulated HCV replication. Rubicon overexpression or administration of bafilomycin A1 or chloroquine, an inhibitor of late-stage autophagy, suppressed autophagy and activated the type 1 IFN pathway. On the other hand, Atg7 knockout suppressed early-stage autophagy and did not activate the type 1 IFN pathway. In livers of humanized liver chimeric mice, HCV infection increased Rubicon and enhanced type 1 IFN signalling. Elimination of HCV in the mice reduced the increase in Rubicon due to HCV infection. The expression levels of Rubicon and IFN-stimulated genes in chronic hepatitis C patients were higher than those in non-B, non-C hepatitis patients. HCV infection increased Rubicon and suppressed hepatocyte autophagy, leading to activation of the intracellular immune response. Rubicon induction is involved in HCV replication via activation of the intracellular immune response.
Investigating causal relationships between Body Mass Index and risk of atopic dermatitis: a Mendelian randomization analysis
Authors: Yew Yik Weng , Loh Marie , Thng Steven Tien Guan , Chambers John C. 
Published: September 2020

AbstractPopulation studies suggest that atopic dermatitis (AD) is associated with an increased risk of obesity, however a causal relationship between these two conditions remains to be established. We therefore use Mendelian randomization (MR) to evaluate whether obesity and AD are causally interlinked. We used summary statistics extracted from genome wide association studies of Body Mass Index (BMI) and AD. MR analysis was performed in both directions to establish the direction of causality between BMI and AD. We find that genetically determined increase in adiposity is associated with increased risk of AD (odds ratio of AD 1.08 [95% CI 1.01 to 1.14; p = 0.015] per unit increase in BMI). Conversely, genetically determined increased risk of AD is not associated with a higher BMI (change in BMI attributable to AD based on genetic information: 0.00; 95% CI − 0.02 to 0.02; p = 0.862). There was no evidence for confounding of these genetic analyses by horizontal pleiotropy. Our results indicate that the association of AD with obesity is likely to reflect a causal role for adiposity in the development of AD. Our findings enhance understanding of the etiology of AD, and the basis for experimental studies to evaluate the mechanistic pathways by which adiposity promotes AD.