bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT
Authors: Dakic Vanja , Minardi Nascimento Juliana , Costa Sartore Rafaela , Maciel Renata de Moraes , de Araujo Draulio B. , Ribeiro Sidarta , Martins-de-Souza Daniel , Rehen Stevens K. 
Published: October 2017

AbstractDimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico analysis reinforced previously reported anti-inflammatory actions of 5-MeO-DMT and revealed modulatory effects on proteins associated with long-term potentiation, the formation of dendritic spines, including those involved in cellular protrusion formation, microtubule dynamics, and cytoskeletal reorganization. Our data offer the first insight about molecular alterations caused by 5-MeO-DMT in human cerebral organoids.
α-Synuclein impairs ferritinophagy in the retinal pigment epithelium: Implications for retinal iron dyshomeostasis in Parkinson’s disease
Authors: Baksi Shounak , Singh Neena 
Published: October 2017

AbstractRetinal degeneration is prominent in Parkinson’s disease (PD), a neuromotor disorder associated with aggregation of α-synuclein (α-syn) in the substantia-nigra (SN). Although α-syn is expressed in the neuroretina, absence of prominent aggregates suggests altered function as the likely cause of retinal pathology. We demonstrate that α-syn impairs ferritinophagy, resulting in the accumulation of iron-rich ferritin in the outer retina in-vivo and retinal-pigment-epithelial (RPE) cells in-vitro. Over-expression of Rab1a restores ferritinophagy, suggesting that α-syn impairs lysosomal function by disrupting the trafficking of lysosomal hydrolases. Surprisingly, upregulation of ferritin in RPE cells by exogenous iron in-vitro stimulated the release of ferritin and α-syn in exosomes, suggesting that iron overload due to impaired ferritinophagy or other cause(s) is likely to initiate prion-like spread of α-syn and ferritin, creating retinal iron dyshomeostasis and associated cytotoxicity. Since over-expression of α-syn is a known cause of PD, these results explain the likely cause of PD-associated retinal degeneration.
Parallels between DNA and collagen – comparing elastic models of the double and triple helix
Authors: Xu Fei , Zheng Hongning , Clauvelin Nicolas , Lu Xiang-Jun , Olson Wilma K. , Nanda Vikas 
Published: October 2017

AbstractMulti-stranded helices are widespread in nature. The interplay of polymeric properties with biological function is seldom discussed. This study probes analogies between structural and mechanical properties of collagen and DNA. We modeled collagen with Eulerian rotational and translational parameters of adjacent rungs in the triple-helix ladder and developed statistical potentials by extracting the dispersion of the parameters from a database of atomic-resolution structures. The resulting elastic model provides a common quantitative way to describe collagen deformations upon interacting with integrins or matrix metalloproteinase and DNA deformations upon protein binding. On a larger scale, deformations in Type I collagen vary with a periodicity consistent with the D-periodic banding of higher-order fibers assemblies. This indicates that morphologies of natural higher-order collagen packing might be rooted in the characteristic deformation patterns.
Comparative genomics of Lactobacillus kefiranofaciens ZW3 and related members of Lactobacillus. spp reveal adaptations to dairy and gut environments
Authors: Xing Zhuqing , Geng Weitao , Li Chao , Sun Ye , Wang Yanping 
Published: October 2017

AbstractIt is important for probiotics that are currently utilized in the dairy industry to have clear genetic backgrounds. In this study, the genetic characteristics of Lactobacillus kefiranofaciens ZW3 were studied by undertaking a comparative genomics study, and key genes for adaptation to different environments were investigated and validated in vitro. Evidence for horizontal gene transfer resulting in strong self-defense mechanisms was detected in the ZW3 genome. We identified a series of genes relevant for dairy environments and the intestinal tract, particularly for extracellular polysaccharide (EPS) production. Reverse transcription-qPCR (RT-qPCR) revealed significant increases in the relative expression of pgm, ugp, and uge during the mid-logarithmic phase, whereas the expression of pgi was higher at the beginning of the stationary phase. The enzymes encoded by these four genes concertedly regulated carbon flux, which in turn modulated the production of EPS precursors. Moreover, ZW3 tolerated pH 3.5 and 3% bile salt and retained cell surface hydrophobicity and auto-aggregation. In conclusion, we explored the potential of ZW3 for utilization in both the dairy industry and in probiotic applications. Additionally, we elucidated the regulation of the relevant genes involved in EPS production.
HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia
Authors: Takiuchi Yoko , Kobayashi Masayuki , Tada Kohei , Iwai Fumie , Sakurada Maki , Hirabayashi Shigeki , Nagata Kayoko , Shirakawa Kotaro , Shindo Keisuke , Yasunaga Jun-ichirou , Murakawa Yasuhiro , Rajapakse Vinodh , Pommier Yves , Matsuoka Masao , Takaori-Kondo Akifumi 
Published: October 2017

AbstractAdult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). We recently reported that abacavir, an anti-HIV-1 drug, potently and selectively kills ATL cells. This effect was attributed to the reduced expression of tyrosyl-DNA-phosphodiesterase 1 (TDP1), a DNA repair enzyme, in ATL cells. However, the molecular mechanism underlying the downregulation of TDP1 in ATL cells remains elusive. Here we identified the core promoter of the TDP1 gene, which contains a conserved nuclear respiratory factor 1 (NRF-1) binding site. Overexpression of NRF-1 increased TDP1-promoter activity, whereas the introduction of dominant-negative NRF-1 repressed such activity. Overexpression of NRF-1 also upregulated endogenous TDP-1 expression, while introduction of shNRF-1 suppressed TDP1 in Jurkat T cells, making them susceptible to abacavir. These results indicate that NRF-1 is a positive transcriptional regulator of TDP1-gene expression. Importantly, we revealed that HTLV-1 bZIP factor (HBZ) protein which is expressed in all ATL cases physically interacts with NRF-1 and inhibits the DNA-binding ability of NRF-1. Taken together, HBZ suppresses TDP1 expression by inhibiting NRF-1 function in ATL cells. The HBZ/NRF-1/TDP1 axis provides new therapeutic targets against ATL and might explain genomic instability leading to the pathogenesis of ATL.
Climates on incidence of childhood type 1 diabetes mellitus in 72 countries
Authors: Chen Yin-ling , Huang Yong-cheng , Qiao Yong-chao , Ling Wei , Pan Yan-hong , Geng Li-jun , Xiao Jian-long , Zhang Xiao-xi , Zhao Hai-lu 
Published: October 2017

AbstractWe are aimed to systematically assess the worldwide trend in incidence of childhood type 1 diabetes mellitus (CT1DM) from 1965 to 2012 and to discuss whether climate affect incidence of CT1DM. We searched the relevant literatures in detail to judge the effect of different climates on incidence of CT1DM. The climates included Mediterranean, monsoon, oceanic, continental, savanna, and rainforest. According to different climates, we further researched relevant factor such as sunshine durations and latitudes. The overall incidence of CT1DM in 72 countries was 11.43 (95% CI 10.31–12.55) per 100,000 children/yr. The incidence of CT1DM in Oceanic climate [10.56 (8.69–12.42)] is highest compared with other climates; the incidence in 40°–66°34′N/S [14.71 (12.30–17.29)] is higher than other latitude groups; the incidence in sunshine durations with 3–4 hours per day [15.17 (11.14–19.20)] is highest compared with other two groups; the incidence of CT1DM from 2000 to 2012 [19.58 (14.55–24.60)] is higher than other periods; all p < 0.01. Incidence of CT1DM was increasing from 1965 to 2012, but incidence in Oceanic climate is higher than other climates. Furthermore, it is higher in centers with higher latitude and lower sunshine durations. The climates might play a key role in inducing CT1DM.
Flexible parental care: Uniparental incubation in biparentally incubating shorebirds
Authors: Bulla Martin , Prüter Hanna , Vitnerová Hana , Tijsen Wim , Sládeček Martin , Alves José A. , Gilg Olivier , Kempenaers Bart 
Published: October 2017

AbstractThe relative investment of females and males into parental care might depend on the population’s adult sex-ratio. For example, all else being equal, males should be the more caring sex if the sex-ratio is male biased. Whether such outcomes are evolutionary fixed (i.e. related to the species’ typical sex-ratio) or whether they arise through flexible responses of individuals to the current population sex-ratio remains unclear. Nevertheless, a flexible response might be limited by the evolutionary history of the species, because one sex may have lost the ability to care or because a single parent cannot successfully raise the brood. Here, we demonstrate that after the disappearance of one parent, individuals from 8 out of 15 biparentally incubating shorebird species were able to incubate uniparentally for 1–19 days (median = 3, N = 69). Moreover, their daily incubation rhythm often resembled that of obligatory uniparental shorebird species. Although it has been suggested that in some biparental shorebirds females desert their brood after hatching, we found both sexes incubating uniparentally. Strikingly, in 27% of uniparentally incubated clutches - from 5 species - we documented successful hatching. Our data thus reveal the potential for a flexible switch from biparental to uniparental care.
Impact of Infectious Disease Consultation on Clinical Management and Outcome of Patients with Bloodstream Infection: a Retrospective Cohort Study
Authors: Tang Guangmin , Huang Liang , Zong Zhiyong 
Published: October 2017

AbstractThe impact of consultation by infectious diseases (ID) physicians on management and outcomes of patients has not been determined in China. We assembled a retrospective cohort of 995 consecutive adult cases with bloodstream infections (BSI) in a major teaching hospital in China. Survival analysis was performed with Cox regression and the Kaplan-Meier curves. Among the 995 patients with BSI, 421 (42.3%) received consultation by ID physicians and 574 (57.7%) did not. ID consultation led to a significant lower hazard of death (hazard ratio [HR], 0.575; P < 0.05) and more appropriate antimicrobial use (95.0% vs 67.6%, P < 0.05). ID consultation was a protective factor among patients with BSI due to Gram-positive (HR, 0.551; P < 0.05) or Gram-negative (HR, 0.331; P < 0.05) bacteria. Multiple ID consultation was a protective factor (HR, 0.51; P < 0.05), while single consultation was not. In conclusion, ID consultation led to significant lower risk for patients with BSI and improved management. Multiple rather than single ID consultations reduced the hazard of death.
Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas
Authors: Palesi Fulvia , De Rinaldis Andrea , Castellazzi Gloria , Calamante Fernando , Muhlert Nils , Chard Declan , Tournier J. Donald , Magenes Giovanni , D’Angelo Egidio , Gandini Wheeler-Kingshott Claudia A. M. 
Published: October 2017

AbstractCerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.
Zebra Finch chicks recognise parental scent, and retain chemosensory knowledge of their genetic mother, even after egg cross-fostering
Authors: Caspers Barbara A. , Hagelin Julie C. , Paul Madeleine , Bock Sandra , Willeke Sandra , Krause E. Tobias 
Published: October 2017

AbstractMechanisms underlying parent-offspring recognition in birds have fascinated researchers for centuries. Yet, the possibility that chicks recognise parental odour at hatching has been completely overlooked, despite the fact that olfaction is one of the first sensory modalities to develop, and social chemosignals occur in avian taxa. Here we show that Zebra Finch chicks (Taeniopygia guttata) are capable of identifying parental odours at hatching. In our first experiment, chicks begged significantly longer in response to the odour of their genetic mother or father compared to the odour of a non-relative of the same sex and reproductive status. In a second experiment, we cross-fostered eggs and tested the response of hatchlings to the scent of genetic vs. foster parents. Chicks from cross-fostered eggs responded significantly more to the odour of their genetic mother than their foster mother, but exhibited no difference in response to genetic vs. foster fathers. This is the first evidence that embryonic altricial birds are capable of acquiring chemosensory knowledge of their parents during early development, and retain chemical familiarity with their genetic mother despite egg cross-fostering. Furthermore our data reveals that kin recognition in birds can develop without any association with a genetic parent at hatching.
The human blood parasite Schistosoma mansoni expresses extracellular tegumental calpains that cleave the blood clotting protein fibronectin
Authors: Wang Qiang , Da’dara Akram A. , Skelly Patrick J. 
Published: October 2017

AbstractSchistosomes are intravascular, parasitic flatworms that cause debilitating disease afflicting >200 million people. Proteins expressed at the host-parasite interface likely play key roles in modifying the worm’s local environment to ensure parasite survival. Proteomic analysis reveals that two proteases belonging to the calpain family (SmCalp1 and SmCalp2) are expressed in the Schistosoma mansoni tegument. We have cloned both; while highly conserved in domain organization they display just 31% amino acid sequence identity. Both display high relative expression in the parasite’s intravascular life forms. Immunolocalization and activity based protein profiling experiments confirm the presence of the enzymes at the host-parasite interface. Living parasites exhibit surface calpain activity that is blocked in the absence of calcium and in the presence of calpain inhibitors (E64c, PD 150606 and calpastatin). While calpains are invariably reported to be exclusively intracellular (except in diseased or injured tissues), our data show that schistosomes display unique, constitutive, functional extracellular calpain activity. Furthermore we show that the worms are capable of cleaving the host blood clotting protein fibronectin and that this activity can be inhibited by E64c. We hypothesize that SmCalp1 and/or SmCalp2 perform this cleavage function to impede blood clot formation around the worms in vivo.
Parkinson’s disease-related DJ-1 functions in thiol quality control against aldehyde attack in vitro
Authors: Matsuda Noriyuki , Kimura Mayumi , Queliconi Bruno Barros , Kojima Waka , Mishima Masaki , Takagi Kenji , Koyano Fumika , Yamano Koji , Mizushima Tsunehiro , Ito Yutaka , Tanaka Keiji 
Published: October 2017

AbstractDJ-1 (also known as PARK7) has been identified as a causal gene for hereditary recessive Parkinson’s disease (PD). Consequently, the full elucidation of DJ-1 function will help decipher the molecular mechanisms underlying PD pathogenesis. However, because various, and sometimes inconsistent, roles for DJ-1 have been reported, the molecular function of DJ-1 remains controversial. Recently, a number of papers have suggested that DJ-1 family proteins are involved in aldehyde detoxification. We found that DJ-1 indeed converts methylglyoxal (pyruvaldehyde)-adducted glutathione (GSH) to intact GSH and lactate. Based on evidence that DJ-1 functions in mitochondrial homeostasis, we focused on the possibility that DJ-1 protects co-enzyme A (CoA) and its precursor in the CoA synthetic pathway from aldehyde attack. Here, we show that intact CoA and β-alanine, an intermediate in CoA synthesis, are recovered from methylglyoxal-adducts by recombinant DJ-1 purified from E. coli. In this process, methylglyoxal is converted to L-lactate rather than the D-lactate produced by a conventional glyoxalase. PD-related pathogenic mutations of DJ-1 (L10P, M26I, A104T, D149A, and L166P) impair or abolish detoxification activity, suggesting a pathological significance. We infer that a key to understanding the biological function of DJ-1 resides in its methylglyoxal-adduct hydrolase activity, which protects low-molecular thiols, including CoA, from aldehydes.
Spatial-temporal distribution of dengue and climate characteristics for two clusters in Sri Lanka from 2012 to 2016
Authors: Sun Wei , Xue Ling , Xie Xiaoxue 
Published: October 2017

AbstractDengue is a vector-borne disease causing high morbidity and mortality in tropical and subtropical countries. Urbanization, globalization, and lack of effective mosquito control have lead to dramatically increased frequency and magnitude of dengue epidemic in the past 40 years. The virus and the mosquito vectors keep expanding geographically in the tropical regions of the world. Using the hot spot analysis and the spatial-temporal clustering method, we investigated the spatial-temporal distribution of dengue in Sri Lanka from 2012 to 2016 to identify spatial-temporal clusters and elucidate the association of climatic factors with dengue incidence. We detected two important spatial-temporal clusters in Sri Lanka. Dengue incidences were predicted by combining historical dengue incidence data with climate data, and hot and cold spots were forecasted using the predicted dengue incidences to identify areas at high risks. Targeting the hot spots during outbreaks instead of all the regions can save resources and time for public health authorities. Our study helps better understand how climatic factors impact spatial and temporal spread of dengue virus. Hot spot prediction helps public health authorities forecast future high risk areas and direct control measures to minimize cost on health, time, and economy.
Genome-wide open chromatin regions and their effects on the regulation of silk protein genes in Bombyx mori
Authors: Zhang Quan , Cheng Tingcai , Jin Shengkai , Guo Youbing , Wu Yuqian , Liu Duolian , Xu Xiaomin , Sun Yueting , Li Zhiqing , He Huawei , Xia Qingyou 
Published: October 2017

AbstractNucleosome-depleted open chromatin regions (OCRs) often harbor transcription factor (TF) binding sites that are associated with active DNA regulatory elements. To investigate the regulation of silk-protein genes, DNA molecules isolated from the silk glands of third-day fifth-instar silkworm larvae and embryo-derived (BmE) cells were subjected to formal dehyde-assisted isolation of regulatory elements (FAIRE) and high-throughput sequencing. In total, 68,000 OCRs were identified, and a number of TF-binding motifs were predicted. In particular, OCRs located near silk-protein genes contained potential binding sites for functional TFs. Moreover, many TFs were found to bind to clusters of OCRs upstream of silk-protein genes, and to regulate the expression of these genes. The expression of silk protein genes may be related not only to regulating TFs (such as fkh, Bmdimm, and Bmsage), but also to developmental and hormone-induced TFs (such as zen, eve, Br, and eip74ef). Elucidation of genome-wide OCRs and their regulatory motifs in silk protein genes will provide valuable data and clues for characterizing the mechanisms of transcriptional control of silk protein genes.
Prokineticin receptor-1-dependent paracrine and autocrine pathways control cardiac tcf21+ fibroblast progenitor cell transformation into adipocytes and vascular cells
Authors: Qureshi Rehana , Kindo Michel , Arora Himanshu , Boulberdaa Mounia , Steenman Marja , Nebigil Canan G. 
Published: October 2017

AbstractCardiac fat tissue volume and vascular dysfunction are strongly associated, accounting for overall body mass. Despite its pathophysiological significance, the origin and autocrine/paracrine pathways that regulate cardiac fat tissue and vascular network formation are unclear. We hypothesize that adipocytes and vasculogenic cells in adult mice hearts may share a common cardiac cells that could transform into adipocytes or vascular lineages, depending on the paracrine and autocrine stimuli. In this study utilizing transgenic mice overexpressing prokineticin receptor (PKR1) in cardiomyocytes, and tcf21ERT-creTM-derived cardiac fibroblast progenitor (CFP)-specific PKR1 knockout mice (PKR1
tcf−/−), as well as FACS-isolated CFPs, we showed that adipogenesis and vasculogenesis share a common CFPs originating from the tcf21+ epithelial lineage. We found that prokineticin-2 is a cardiomyocyte secretome that controls CFP transformation into adipocytes and vasculogenic cells in vivo and in vitro. Upon HFD exposure, PKR1
tcf−/− mice displayed excessive fat deposition in the atrioventricular groove, perivascular area, and pericardium, which was accompanied by an impaired vascular network and cardiac dysfunction. This study contributes to the cardio-obesity field by demonstrating that PKR1 via autocrine/paracrine pathways controls CFP–vasculogenic- and CFP-adipocyte-transformation in adult heart. Our study may open up new possibilities for the treatment of metabolic cardiac diseases and atherosclerosis.