bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphisms in CRYBB2 encoding βB2-crystallin are associated with antisaccade performance and memory function
Authors: Giegling Ina , Hartmann Annette M. , Genius Just , Konte Bettina , Maul Stephan , Straube Andreas , Eggert Thomas , Mulert Christoph , Leicht Gregor , Karch Susanne , Hegerl Ulrich , Pogarell Oliver , Hölter Sabine M. , Möller Hans-Jürgen , Graw Jochen , Rujescu Dan
Published: April 2020

βB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens before it was detected in various brain regions of the mouse, including the hippocampus and the cerebral cortex. Mutations in the mouse Crybb2 gene lead to alterations of sensorimotor gating measured as prepulse inhibition (PPI) and reduced hippocampal size, combined with an altered number of parvalbumin-positive GABAergic interneurons. Decreased PPI and alterations of parvalbumin-positive interneurons are also endophenotypes that typically occur in schizophrenia. To verify the results found in mice, we genotyped 27 single nucleotide polymorphisms (SNPs) within the CRYBB2 gene and its flanking regions and investigated different schizophrenia typical endophenotypes in a sample of 510 schizophrenia patients and 1322 healthy controls. In the case-control study, no association with schizophrenia was found. However, 3 of the 4 investigated haplotype blocks indicated a decreased CRYBB2 mRNA expression. Two of these blocks were associated with poorer antisaccade task performance and altered working memory-linked functional magnetic resonance imaging signals. For the two haplotypes associated with antisaccade performance, suggestive evidence was found with visual memory and in addition, haplotype block 4 showed a nominally significant association with reduced sensorimotor gating, measured as P50 ratio. These results were not schizophrenia-specific, but could be detected in a combined sample of patients and healthy controls. This is the first study to demonstrate the importance of βB2-crystallin for antisaccade performance and memory function in humans and therefore provides implications for βB2-crystallin function in the human brain.
LncRNA GOLGA2P10 is induced by PERK/ATF4/CHOP signaling and protects tumor cells from ER stress-induced apoptosis by regulating Bcl-2 family members
Authors: Wu Meng-Zhi , Fu Tao , Chen Jin-Xi , Lin Ying-Ying , Yang Jin-E , Zhuang Shi-Mei
Published: April 2020

Elevated endoplasmic reticulum (ER) stress is frequently observed in cancers, whereas sustained ER stress may trigger apoptosis. How cancer cells escape from ER stress-induced apoptosis remain unclear. Here, we found that a pseudogene-derived lncRNA, Golgin A2 pseudogene 10 (GOLGA2P10), was frequently upregulated in HCC tissues and significantly elevated in hepatoma cells treated with ER stress inducers, such as tunicamycin and thapsigargin. Higher GOLGA2P10 level was correlated with shorter recurrence-free survival of HCC patients. Upon ER stress, CHOP directly bound to the promoter of GOLGA2P10 and induced its transcription via the PERK/ATF4/CHOP pathway. Interestingly, the ER stress inducer-stimulated apoptosis was promoted by silencing GOLGA2P10 but was antagonized by overexpressing GOLGA2P10. Both gain- and loss-of-function analyses disclosed that GOLGA2P10 increased BCL-xL protein level, promoted BAD phosphorylation, and conferred tumor cells with resistance to ER stress-induced apoptosis. Moreover, BCL-xL overexpression or BAD knockdown abrogated the apoptosis-promoting effect of GOLGA2P10 silencing. Consistently, the Ser75Ala mutation in BAD, which caused phosphorylation-resistance, further enhanced the promoting effect of BAD in tunicamycin-induced apoptosis. These results suggest that ER stress induces GOLGA2P10 transcription through the PERK/ATF4/CHOP pathway, and upregulation of GOLGA2P10 protects tumor cells from the cytotoxic effect of persistent ER stress in tumor microenvironment by regulating Bcl-2 family members, which highlight GOLGA2P10 as a potential target for anticancer therapy.
E2F1 mediated DDX11 transcriptional activation promotes hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway
Authors: Yu Yan , Zhao Dan , Li Kongfei , Cai Yubo , Xu Penglin , Li Rui , Li Juan , Chen Xiaolong , Chen Ping , Cui Guangying
Published: April 2020

The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was positively correlated with large tumor size, tumor multiplicity, late tumor-node-metastasis (TNM) stage and poor prognosis. Additional, gain-of-function and loss-of-function experimental results revealed that DDX11 overexpression promoted HCC cell proliferation, migration, invasion and inhibited cell apoptosis in vitro. Overexpression of DDX11 also enhanced HCC tumorigenicity in vivo. Furthermore, DDX11 was transcriptionally regulated by transcription factor E2F1 in HCC, as demonstrated by chromatin immunoprecipitation (Ch-IP) and luciferase reporter assays. Mechanistically, E2F1/DDX11 axis promoted HCC cell proliferation, migration and invasion, at least in part, through activating PI3K/AKT/mTOR signaling pathway. Conclusively, our study demonstrates that E2F1-enhanced DDX11 expression promotes HCC progression through PI3K/AKT/mTOR pathway and DDX11 might be a potential therapeutic and prognostic target for HCC treatment.
Oceanic crust recycling controlled by weakening at slab edges
Authors: Munch Jessica , Gerya Taras , Ueda Kosuke
Published: April 2020

Retreating subduction zones such as the Lesser Antilles, Gibraltar and Scotia have been migrating towards the Atlantic Ocean by cutting their way through the oceanic crust. This spontaneously retreating subduction is enabled by the development of faults at the edges of the slab, but the physical mechanisms controlling fault propagation and direction remain unknown. Here, using 3D numerical subduction models we show that oceanic lithosphere recycling is mainly controlled by the intensity of strain-induced weakening of fractures forming at the edges of the slab. Intense strain-induced weakening causes predominantly brittle fault propagation and slab narrowing until detachment. Without weakening, preponderantly ductile slab edge propagation occurs, which causes slab widening. This rheological control is not affected by the proximity of non-weakened passive continental margins. Natural examples suggest that slab edges follow convergent paths that could be controlled by fractures weakening due to deep water penetration into the oceanic lithosphere.
Non-linear interaction modulates global extreme sea levels, coastal flood exposure, and impacts
Authors: Arns Arne , Wahl Thomas , Wolff Claudia , Vafeidis Athanasios T. , Haigh Ivan D. , Woodworth Philip , Niehüser Sebastian , Jensen Jürgen
Published: April 2020

We introduce a novel approach to statistically assess the non-linear interaction of tide and non-tidal residual in order to quantify its contribution to extreme sea levels and hence its role in modulating coastal protection levels, globally. We demonstrate that extreme sea levels are up to 30% (or 70 cm) higher if non-linear interactions are not accounted for (e.g., by independently adding astronomical and non-astronomical components, as is often done in impact case studies). These overestimates are similar to recent sea-level rise projections to 2100 at some locations. Furthermore, we further find evidence for changes in this non-linear interaction over time, which has the potential for counteracting the increasing flood risk associated with sea-level rise and tidal and/or meteorological changes alone. Finally, we show how accounting for non-linearity in coastal impact assessment modulates coastal exposure, reducing recent estimates of global coastal flood costs by ~16%, and population affected by ~8%.
Recent hemispheric asymmetry in global ocean warming induced by climate change and internal variability
Authors: Rathore Saurabh , Bindoff Nathaniel L. , Phillips Helen E. , Feng Ming
Published: April 2020

Recent research shows that 90% of the net global ocean heat gain during 2005–2015 was confined to the southern hemisphere with little corresponding heat gain in the northern hemisphere ocean. We propose that this heating pattern of the ocean is driven by anthropogenic climate change and an asymmetric climate variation between the two hemispheres. This asymmetric variation is found in the pre-industrial control simulations from 11 climate models. While both layers (0–700 m and 700–2000 m) experience steady anthropogenic warming, the 0–700 m layer experiences large internal variability, which primarily drives the observed hemispheric asymmetry of global ocean heat gain in 0–2000 m layer. We infer that the rate of global ocean warming is consistent with the climate simulations for this period. However, the observed hemispheric asymmetry in heat gain can be explained by the Earth’s internal climate variability without invoking alternate hypotheses, such as asymmetric aerosol loading.
Polyamide nanofiltration membrane with highly uniform sub-nanometre pores for sub-1 Å precision separation
Authors: Liang Yuanzhe , Zhu Yuzhang , Liu Cheng , Lee Kueir-Rarn , Hung Wei-Song , Wang Zhenyi , Li Youyong , Elimelech Menachem , Jin Jian , Lin Shihong
Published: April 2020

Separating molecules or ions with sub-Angstrom scale precision is important but technically challenging. Achieving such a precise separation using membranes requires Angstrom scale pores with a high level of pore size uniformity. Herein, we demonstrate that precise solute-solute separation can be achieved using polyamide membranes formed via surfactant-assembly regulated interfacial polymerization (SARIP). The dynamic, self-assembled network of surfactants facilitates faster and more homogeneous diffusion of amine monomers across the water/hexane interface during interfacial polymerization, thereby forming a polyamide active layer with more uniform sub-nanometre pores compared to those formed via conventional interfacial polymerization. The polyamide membrane formed by SARIP exhibits highly size-dependent sieving of solutes, yielding a step-wise transition from low rejection to near-perfect rejection over a solute size range smaller than half Angstrom. SARIP represents an approach for the scalable fabrication of ultra-selective membranes with uniform nanopores for precise separation of ions and small solutes.
Stress gates an astrocytic energy reservoir to impair synaptic plasticity
Authors: Murphy-Royal Ciaran , Johnston April D. , Boyce Andrew K. J. , Diaz-Castro Blanca , Institoris Adam , Peringod Govind , Zhang Oliver , Stout Randy F. , Spray David C. , Thompson Roger J. , Khakh Baljit S. , Bains Jaideep S. , Gordon Grant R.
Published: April 2020

Astrocytes support the energy demands of synaptic transmission and plasticity. Enduring changes in synaptic efficacy are highly sensitive to stress, yet whether changes to astrocyte bioenergetic control of synapses contributes to stress-impaired plasticity is unclear. Here we show in mice that stress constrains the shuttling of glucose and lactate through astrocyte networks, creating a barrier for neuronal access to an astrocytic energy reservoir in the hippocampus and neocortex, compromising long-term potentiation. Impairing astrocytic delivery of energy substrates by reducing astrocyte gap junction coupling with dominant negative connexin 43 or by disrupting lactate efflux was sufficient to mimic the effects of stress on long-term potentiation. Furthermore, direct restoration of the astrocyte lactate supply alone rescued stress-impaired synaptic plasticity, which was blocked by inhibiting neural lactate uptake. This gating of synaptic plasticity in stress by astrocytic metabolic networks indicates a broader role of astrocyte bioenergetics in determining how experience-dependent information is controlled.
Dynamic co-catalysis of Au single atoms and nanoporous Au for methane pyrolysis
Authors: Xi Wei , Wang Kai , Shen Yongli , Ge Mengke , Deng Ziliang , Zhao Yunfeng , Cao Qiue , Ding Yi , Hu Guangzhi , Luo Jun
Published: April 2020

Nanocatalysts and single-atom catalysts are both vital for heterogeneous catalysis. They are recognized as two different categories of catalysts. Nevertheless, recent theoretical works have indicated that Au nanoparticles/clusters release Au single atoms in CO oxidation, and they co-catalyze the oxidation. However, to date, neither experimental evidence for the co-catalysis nor direct observations on any heterogeneous catalysis process of single-atom catalysts are reported. Here, the dynamic process of nanoporous Au to catalyze methane pyrolysis is monitored by in situ transmission electron microscopy with high spatial–temporal resolutions. It demonstrates that nanoporous Au surfaces partially disintegrate, releasing Au single atoms. As demonstrated by DFT calculation, the single atoms could co-catalyze the reaction with nanoporous Au. Moreover, the single atoms dynamically aggregate into nanoparticles, which re-disintegrate back to single atoms. This work manifests that under certain conditions, the heterogeneous catalysis processes of nanocatalysts and single-atom catalysts are not independent, where their dynamic co-catalysis exists.
Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis
Authors: Tajik Narges , Frech Michael , Schulz Oscar , Schälter Fabian , Lucas Sébastien , Azizov Vugar , Dürholz Kerstin , Steffen Franziska , Omata Yasunori , Rings Andreas , Bertog Marko , Rizzo Aroldo , Iljazovic Aida , Basic Marijana , Kleyer Arnd , Culemann Stephan , Krönke Gerhard , Luo Yubin , Überla Klaus , Gaipl Udo S. , Frey Benjamin , Strowig Till , Sarter Kerstin , Bischoff Stephan C. , Wirtz Stefan , Cañete Juan D. , Ciccia Francesco , Schett Georg , Zaiss Mario M.
Published: April 2020

Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function.
Direct evidence of boosted oxygen evolution over perovskite by enhanced lattice oxygen participation
Authors: Pan Yangli , Xu Xiaomin , Zhong Yijun , Ge Lei , Chen Yubo , Veder Jean-Pierre Marcel , Guan Daqin , O’Hayre Ryan , Li Mengran , Wang Guoxiong , Wang Hao , Zhou Wei , Shao Zongping
Published: April 2020

The development of oxygen evolution reaction (OER) electrocatalysts remains a major challenge that requires significant advances in both mechanistic understanding and material design. Recent studies show that oxygen from the perovskite oxide lattice could participate in the OER via a lattice oxygen-mediated mechanism, providing possibilities for the development of alternative electrocatalysts that could overcome the scaling relations-induced limitations found in conventional catalysts utilizing the adsorbate evolution mechanism. Here we distinguish the extent to which the participation of lattice oxygen can contribute to the OER through the rational design of a model system of silicon-incorporated strontium cobaltite perovskite electrocatalysts with similar surface transition metal properties yet different oxygen diffusion rates. The as-derived silicon-incorporated perovskite exhibits a 12.8-fold increase in oxygen diffusivity, which matches well with the 10-fold improvement of intrinsic OER activity, suggesting that the observed activity increase is dominantly a result of the enhanced lattice oxygen participation.
Nitrogen starvation reveals the mitotic potential of mutants in the S/MAPK pathways
Authors: Makarenko Rostyslav , Denis Claire , Francesconi Stefania , Gangloff Serge , Arcangioli Benoît
Published: April 2020

The genetics of quiescence is an emerging field compared to that of growth, yet both states generate spontaneous mutations and genetic diversity fueling evolution. Reconciling mutation rates in dividing conditions and mutation accumulation as a function of time in non-dividing situations remains a challenge. Nitrogen-starved fission yeast cells reversibly arrest proliferation, are metabolically active and highly resistant to a variety of stresses. Here, we show that mutations in stress- and mitogen-activated protein kinase (S/MAPK) signaling pathways are enriched in aging cultures. Targeted resequencing and competition experiments indicate that these mutants arise in the first month of quiescence and expand clonally during the second month at the expense of the parental population. Reconstitution experiments show that S/MAPK modules mediate the sacrifice of many cells for the benefit of some mutants. These findings suggest that non-dividing conditions promote genetic diversity to generate a social cellular environment prone to kin selection.
Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration
Authors: Kim Yeonjoo , Lee Jiyoung , Seppala Maisa , Cobourne Martyn T. , Kim Soo-Hyun
Published: April 2020

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche.
Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
Authors: Seo Ji A , Kang Min-Cheol , Yang Won-Mo , Hwang Won Min , Kim Sang Soo , Hong Soo Hyun , Heo Jee-In , Vijyakumar Achana , Pereira de Moura Leandro , Uner Aykut , Huang Hu , Lee Seung Hwan , Lima Inês S. , Park Kyong Soo , Kim Min Seon , Dagon Yossi , Willnow Thomas E. , Aroda Vanita , Ciaraldi Theodore P. , Henry Robert R. , Kim Young-Bum
Published: April 2020

Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.
Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig
Authors: Lei Changhai , Qian Kewen , Li Tian , Zhang Sheng , Fu Wenyan , Ding Min , Hu Shi
Published: April 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2.
Tunable chemical complexity to control atomic diffusion in alloys
Authors: Osetsky Yuri , Barashev Alexander V. , Béland Laurent K. , Yao Zhongwen , Ferasat Keyvan , Zhang Yanwen
Published: April 2020

In this paper we report a new fundamental understanding of chemically-biased diffusion in Ni–Fe random alloys that is tuned/controlled by the intrinsic quantifiable chemical complexity. Development of radiation-tolerant alloys has been a long-standing challenge. Here we show how intrinsic chemical complexity can be utilized to guide the atomic diffusion and suppress radiation damage. The influence of chemical complexity is shown by the example of interstitial atom (IA) diffusion that is the most important defect in radiation effects. We use μs-scale molecular dynamics to reveal sluggish diffusion and percolation of IAs in concentrated Ni–Fe alloys. We develop a mean field diffusion model to take into account the effect of migrating defect energy properties on diffusion percolation, which is verified by a new kinetic Monte Carlo approach addressing detailed processes. We demonstrate that the local variations in the ground state energy of IA configurations in alloys, reflecting the chemical difference between alloying components, drives the percolation effects for atomic diffusion. Percolation, chemically-biased and sluggish diffusion are phenomena that are directly related to the chemical complexity intrinsically to multicomponent alloys.
Association between Hepatitis B Virus Infection and Metabolic Syndrome in Southwest China: A Cross-sectional Study
Authors: Yan Li-Bo , Liao Juan , Han Ning , Zhou Ling-Yun , Wang Xue-Er , Wang You-Juan , Tang Hong
Published: April 2020

The correlation between hepatitis B virus (HBV) infection and metabolic syndrome (MetS) remains to be clarified. In this study, we explored this association in a large population in Southwest China. This was a cross-sectional study, with pooled adult health data. Multivariate logistic regression analysis, controlling for age, sex, HBV status, alanine aminotransferase, and fatty liver, was used to identify predictor(s) of MetS. Of the 96,175 participants, positive HBV was identified in 7984 (8.30%) and MetS in 12,092 (12.57%). The MetS prevalence was lower among HBV positive than negative individuals (11.64% versus 12.66%, P < 0.001). The adjusted odds (aOR) of positive HBV among individuals with MetS was 0.841 (95% confidence interval (CI), 0.771–0.916) in men and 0.834 (95% CI, 0.672–0.925) in women. Elevated triglyceride level, a component of MetS, was inversely associated with HBV status in both men and women: aOR, 0.551 (95% CI, 0.514–0.590) and 0.683 (95% CI, 0.605–0.769), respectively. Among HBV positive individuals, liver cirrhosis was more common among those with than without MetS (4.83% versus 2.93%, respectively; P = 0.002). HBsAg-seropositive are inversely associated with MetS, especially elevated triglycerides. Liver cirrhosis was more common among HBV infection patients with MetS.
Influence of micropatterned substrates on keratocyte phenotype
Authors: Bhattacharjee Promita , Cavanagh Brenton L. , Ahearne Mark
Published: April 2020

Substrate topographic patterning is a powerful tool that can be used to manipulate cell shape and orientation. To gain a better understanding of the relationship between surface topography and keratocyte behavior, surface patterns consisting of linear aligned or orthogonally aligned microchannels were used. Photolithography and polymer molding techniques were used to fabricate micropatterns on the surface of polydimethylsiloxane (PDMS). Cells on linear aligned substrates were elongated and aligned in the channel direction, while cells on orthogonal substrates had a more spread morphology. Both linear and orthogonal topographies induced chromatin condensation and resulted in higher expressions of keratocyte specific genes and sulfated glycosaminoglycans (sGAG), compared with non-patterned substrates. However, despite differences in cell morphology and focal adhesions, many genes associated with a native keratocyte phenotype, such as keratocan and ALDH3A1, remain unchanged on the different patterned substrates. This information could be used to optimize substrates for keratocyte culture and to develop scaffolds for corneal regeneration.
Neck-specific exercise for radiating pain and neurological deficits in chronic whiplash, a 1-year follow-up of a randomised clinical trial
Authors: Ludvigsson Maria Landén , Peterson Gunnel , Peolsson Anneli
Published: April 2020

Up to 90% of people with neurological deficits following whiplash injury report chronic symptoms. A recent unique study of neck-specific exercise showed positive results (post-intervention at 12 weeks), regarding arm pain and neurological deficits in people with chronic whiplash associated disorders (WAD). This 1-year follow-up of that randomised controlled study with assessor blinding aimed to examine whether neck-specific exercise with (NSEB) or without (NSE) a behavioural approach has long-term benefits over physical activity prescription (PPA) regarding arm pain and neurological deficits (n = 171). Interventions were: NSE, NSEB, or PPA. Follow-up of arm pain, paraesthesia bothersomeness (questionnaires) and clinical neurological tests were performed after 3, 6 and 12 months and analysed with Linear Mixed Models and General Estimating Equations. The NSE and/or NSEB groups reported significantly less pain and paraesthesia bothersomeness as well as higher odds of normal key muscle arm strength and of normal upper limb neural tension over the year (all p < 0.03), compared with PPA. In conclusion, results suggest that neck-specific exercise with or without a behavioural approach may have persisting long term benefits over PPA regarding arm pain and clinical signs associated with neurological deficits in chronic WAD.
Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro
Authors: Shigematsu Nao , Kawashiri Takehiro , Kobayashi Daisuke , Shimizu Shiori , Mine Keisuke , Hiromoto Shiori , Uchida Mayako , Egashira Nobuaki , Shimazoe Takao
Published: April 2020

Oxaliplatin is a platinum-based antineoplastic drug commonly used for treating colorectal, gastric, and pancreatic cancer. However, it frequently causes peripheral neuropathy as dose-limiting toxicity and is lacking a strategy for prevention. Alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, is an oral antidiabetic drug. Previous studies have shown that DPP-4 inhibitors have pleiotropic effects, including neuroprotection. In this study, we investigated the effects of alogliptin on oxaliplatin-induced peripheral neuropathy using in vitro and in vivo models. In PC12 cells, alogliptin attenuated neurite disorders induced by oxaliplatin and cisplatin. The repeated injection of oxaliplatin caused mechanical allodynia and axonal degeneration of the sciatic nerve in rats. These neuropathies were ameliorated by co-administration of alogliptin. Moreover, alogliptin did not attenuate tumor cytotoxicity of oxaliplatin in the cultured colon, gastric, or pancreatic cancer cell lines and tumor-bearing mice. These findings suggest that alogliptin may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.
Control of cell colony growth by contact inhibition
Authors: Schnyder Simon K. , Molina John J. , Yamamoto Ryoichi
Published: April 2020

Contact inhibition is a cell property that limits the migration and proliferation of cells in crowded environments. Here we investigate the growth dynamics of a cell colony composed of migrating and proliferating cells on a substrate using a minimal model that incorporates the mechanisms of contact inhibition of locomotion and proliferation. We find two distinct regimes. At early times, when contact inhibition is weak, the colony grows exponentially in time, fully characterised by the proliferation rate. At long times, the colony boundary moves at a constant speed, determined only by the migration speed of a single cell and independent of the proliferation rate. Further, the model demonstrates how cell-cell alignment speeds up colony growth. Our model illuminates how simple local mechanical interactions give rise to contact inhibition, and from this, how cell colony growth is self-organised and controlled on a local level.
Structural dynamics effects on the electronic predissociation of alkyl iodides
Authors: Murillo-Sánchez Marta L. , Zanchet Alexandre , Marggi Poullain Sonia , González-Vázquez Jesús , Bañares Luis
Published: April 2020

The correlation between chemical structure and predissociation dynamics has been evaluated for a series of linear and branched alkyl iodides with increasing structural complexity by means of femtosecond time-resolved velocity map imaging experiments following excitation on the second absorption band (B-band) at around 201 nm. The time-resolved images for the iodine fragment are reported and analyzed in order to extract electronic predissociation lifetimes and the temporal evolution of the anisotropy while the experimental results are supported by ab initio calculations of the potential energy curves as a function of the C-I distance. Remarkable similarities are observed for all molecules consistent with a major predissociation of the initially populated bound Rydberg states 6A″ and 7A′ through a crossing with the purely repulsive states 7A″, 8A′ and 8A″ leading to a major R + I*(2P1/2) (R = CH3, C2H5, n-C3H7, n-C4H9, i-C3H7 and t-C4H9) dissociation channel. The reported electronic predissociation lifetimes are found to decrease for an increasing size of the linear radical, reflecting the shifts observed in the position of the crossings in the potential energy curves, and very likely a greater non-adiabatic coupling between the initially populated Rydberg states and the repulsive states leading to dissociation induced by other coordinates associated to key vibrational normal modes. The loss of anisotropy is fully accounted for by the parent molecular rotation during predissociation and the rotational temperature of the parent molecule in the molecular beam is reasonably derived.
Simultaneous optimization of parameters influencing organic mulch test using response surface methodology
Authors: Shojaei Saeed , Ardakani Mohammad Ali Hakimzadeh , Sodaiezadeh Hamid , jafari Mohammad , afzali Seyed fakhreddin
Published: April 2020

Wind erosion could be regarded as one of the most important phenomena especially in arid lands in the globe, which destroys vast areas with its rapid growth. Due to global droughts and climate change, vegetation is weakened and soil particles are more easily exposed to wind erosion. Today, various methods have been developed to control wind erosion. One of the most commonly used methods is the use of mulch. Mulch has several types (physical-chemical). The purpose of this research is to make organic mulch with inexpensive and available compounds to prevent environmental pollution as well as preventing wind erosion. For this purpose, Chaff, Manure, Biosolids and Black Strap mixture were used. The surface response method (RSM) was utilized to perform the relevant tests and create optimal situation. In this study, the central composite design (CCD) in RSM modeling was applied to make the optimal experimental conditions of erosion and penetration resistance. The effect of concentration of Chaff, Manure, Biosolids and Black Strap, was evaluated in erosion and penetration resistance and each variable was coded at five levels. The optimum values for penetration resistance of 1.8 (kg/cm2) for Chaff, Manure, Biosolids, and Black Strap, were 11.32, 15.72, 19.23 and 4.37 g, respectively. Also, the optimum values of mulch combination for wind erosion of 1.8 kg/cm2 for Chaff, Manure, Biosolids, and Black Strap, were 12.49, 19.95, 16.71 and 7.15 g, respectively. By increasing the use of these compounds, adhesion and erosion resistance increased and more consumption of Black Strap had a reverse effect. This was due to the loosing of soil particles and creating exponential mode in graphs. According to the results, no particular distinction was found between predicted data by Design-Expert software and experimental data and simulation results can be expressed reliably.
SOX3 promotes generation of committed spermatogonia in postnatal mouse testes
Authors: McAninch Dale , Mäkelä Juho-Antti , La Hue M. , Hughes James N. , Lovell-Badge Robin , Hobbs Robin M. , Thomas Paul Q.
Published: April 2020

SOX3 is a transcription factor expressed within the developing and adult nervous system where it mostly functions to help maintain neural precursors. Sox3 is also expressed in other locations, notably within the spermatogonial stem/progenitor cell population in postnatal testis. Independent studies have shown that Sox3 null mice exhibit a spermatogenic block as young adults, the mechanism of which remains poorly understood. Using a panel of spermatogonial cell marker genes, we demonstrate that Sox3 is expressed within the committed progenitor fraction of the undifferentiated spermatogonial pool. Additionally, we use a Sox3 null mouse model to define a potential role for this factor in progenitor cell function. We demonstrate that Sox3 expression is required for transition of undifferentiated cells from a GFRα1+ self-renewing state to the NGN3 + transit-amplifying compartment. Critically, using chromatin immunoprecipitation, we demonstrate that SOX3 binds to a highly conserved region in the Ngn3 promoter region in vivo, indicating that Ngn3 is a direct target of SOX3. Together these studies indicate that SOX3 functions as a pro-commitment factor in spermatogonial stem/progenitor cells.
Unravelling the consequences of the bacteriophages in human samples
Authors: Blanco-Picazo Pedro , Fernández-Orth Dietmar , Brown-Jaque Maryury , Miró Elisenda , Espinal Paula , Rodríguez-Rubio Lorena , Muniesa Maite , Navarro Ferran
Published: April 2020

Bacteriophages are abundant in human biomes and therefore in human clinical samples. Although this is usually not considered, they might interfere with the recovery of bacterial pathogens at two levels: 1) by propagating in the enrichment cultures used to isolate the infectious agent, causing the lysis of the bacterial host and 2) by the detection of bacterial genes inside the phage capsids that mislead the presence of the bacterial pathogen. To unravel these interferences, human samples (n = 271) were analyzed and infectious phages were observed in 11% of blood culture, 28% of serum, 45% of ascitic fluid, 14% of cerebrospinal fluid and 23% of urine samples. The genetic content of phage particles from a pool of urine and ascitic fluid samples corresponded to bacteriophages infecting different bacterial genera. In addition, many bacterial genes packaged in the phage capsids, including antibiotic resistance genes and 16S rRNA genes, were detected in the viromes. Phage interference can be minimized applying a simple procedure that reduced the content of phages up to 3 logs while maintaining the bacterial load. This method reduced the detection of phage genes avoiding the interference with molecular detection of bacteria and reduced the phage propagation in the cultures, enhancing the recovery of bacteria up to 6 logs.
Modulating dream experience: Noninvasive brain stimulation over the sensorimotor cortex reduces dream movement
Authors: Noreika Valdas , Windt Jennifer M. , Kern Markus , Valli Katja , Salonen Tiina , Parkkola Riitta , Revonsuo Antti , Karim Ahmed A. , Ball Tonio , Lenggenhager Bigna
Published: April 2020

Recently, cortical correlates of specific dream contents have been reported, such as the activation of the sensorimotor cortex during dreamed hand clenching. Yet, despite a close resemblance of such activation patterns to those seen during the corresponding wakeful behaviour, the causal mechanisms underlying specific dream contents remain largely elusive. Here, we aimed to investigate the causal role of the sensorimotor cortex in generating movement and bodily sensations during REM sleep dreaming. Following bihemispheric transcranial direct current stimulation (tDCS) or sham stimulation, guided by functional mapping of the primary motor cortex, naive participants were awakened from REM sleep and responded to a questionnaire on bodily sensations in dreams. Electromyographic (EMG) and electroencephalographic (EEG) recordings were used to quantify physiological changes during the preceding REM period. We found that tDCS, compared to sham stimulation, significantly decreased reports of dream movement, especially of repetitive actions. Other types of bodily experiences, such as tactile or vestibular sensations, were not affected by tDCS, confirming the specificity of stimulation effects to movement sensations. In addition, tDCS reduced EEG interhemispheric coherence in parietal areas and affected the phasic EMG correlation between both arms. These findings show that a complex temporal reorganization of the motor network co-occurred with the reduction of dream movement, revealing a link between central and peripheral motor processes and movement sensations of the dream self. tDCS over the sensorimotor cortex interferes with dream movement during REM sleep, which is consistent with a causal contribution to dream experience and has broader implications for understanding the neural basis of self-experience in dreams.
Specific adsorption sites and conditions derived by thermal decomposition of activated carbons and adsorbed carbamazepine
Authors: Dittmann Daniel , Eisentraut Paul , Goedecke Caroline , Wiesner Yosri , Jekel Martin , Ruhl Aki Sebastian , Braun Ulrike
Published: April 2020

The adsorption of organic micropollutants onto activated carbon is a favourable solution for the treatment of drinking water and wastewater. However, these adsorption processes are not sufficiently understood to allow for the appropriate prediction of removal processes. In this study, thermogravimetric analysis, alongside evolved gas analysis, is proposed for the characterisation of micropollutants adsorbed on activated carbon. Varying amounts of carbamazepine were adsorbed onto three different activated carbons, which were subsequently dried, and their thermal decomposition mechanisms examined. The discovery of 55 different pyrolysis products allowed differentiations to be made between specific adsorption sites and conditions. However, the same adsorption mechanisms were found for all samples, which were enhanced by inorganic constituents and oxygen containing surface groups. Furthermore, increasing the loadings led to the evolution of more hydrated decomposition products, whilst parts of the carbamazepine molecules were also integrated into the carbon structure. It was also found that the chemical composition, especially the degree of dehydration of the activated carbon, plays an important role in the adsorption of carbamazepine. Hence, it is thought that the adsorption sites may have a higher adsorption energy for specific adsorbates, when the activated carbon can then potentially increase its degree of graphitisation.
Efficient differentiation and polarization of primary cultured neurons on poly(lactic acid) scaffolds with microgrooved structures
Authors: Otomo Asako , Ueda Mahoko Takahashi , Fujie Toshinori , Hasebe Arihiro , Suematsu Yoshitaka , Okamura Yosuke , Takeoka Shinji , Hadano Shinji , Nakagawa So
Published: April 2020

Synthetic biodegradable polymers including poly(lactic acid) (PLA) are attractive cell culture substrates because their surfaces can be micropatterned to support cell adhesion. The cell adhesion properties of a scaffold mainly depend on its surface chemical and structural features; however, it remains unclear how these characteristics affect the growth and differentiation of cultured cells or their gene expression. In this study, we fabricated two differently structured PLA nanosheets: flat and microgrooved. We assessed the growth and differentiation of mouse primary cultured cortical neurons on these two types of nanosheets after pre-coating with poly-D-lysine and vitronectin. Interestingly, prominent neurite bundles were formed along the grooves on the microgrooved nanosheets, whereas thin and randomly extended neurites were only observed on the flat nanosheets. Comparative RNA sequencing analyses revealed that the expression of genes related to postsynaptic density, dendritic shafts, and asymmetric synapses was significantly and consistently up-regulated in cells cultured on the microgrooved nanosheets when compared with those cultured on the flat nanosheets. These results indicate that microgrooved PLA nanosheets can provide a powerful means of establishing a culture system for the efficient and reproducible differentiation of neurons, which will facilitate future investigations of the molecular mechanisms underlying the pathogenesis of neurological disorders.
Forecasting mangrove ecosystem degradation utilizing quantifiable eco-physiological resilience -A study from Indian Sundarbans
Authors: Begam Mst Momtaj , Chowdhury Rajojit , Sutradhar Tapan , Mukherjee Chandan , Chatterjee Kiranmoy , Basak Sandip Kumar , Ray Krishna
Published: April 2020

Sundarbans mangrove forest, the world’s largest continuous mangrove forests expanding across India and Bangladesh, in recent times, is immensely threatened by degradation stress due to natural stressors and anthropogenic disturbances. The degradation across the 19 mangrove forests in Indian Sundarbans was evaluated by eight environmental criteria typical to mangrove ecosystem. In an attempt to find competent predictors for mangrove ecosystem degradation, key eco-physiological resilience trait complex specific for mangroves from 4922 individuals for physiological analyses with gene expression and 603 individuals for leaf tissue distributions from 16 mangroves and 15 associate species was assessed along the degradation gradient. The degradation data was apparently categorized into four and CDFA discriminates 97% of the eco-physiological resilience data into corresponding four groups. Predictive Bayesian regression models and mixed effects models indicate osmolyte accumulation and thickness of water storage tissue as primary predictors of each of the degradation criteria that appraise the degradation status of mangrove ecosystem. RDA analyses well represented response variables of degradation explained by explanatory resilience variables. We hypothesize that with the help of our predictive models the policy makers could trace even the cryptic process of mangrove degradation and save the respective forests in time by proposing appropriate action plans.
Competing effects of soil fertility and toxicity on tropical greening
Authors: Fisher Joshua B. , Perakalapudi Naga  V. , Turner Benjamin L. , Schimel David S. , Cusack Daniela F.
Published: April 2020

Tropical forests are expected to green up with increasing atmospheric CO2 concentrations, but primary productivity may be limited by soil nutrient availability. However, rarely have canopy-scale measurements been assessed against soil measurements in the tropics. Here, we sought to assess remotely sensed canopy greenness against steep soil nutrient gradients across 50 1-ha mature forest plots in Panama. Contrary to expectations, increases in in situ extractable soil phosphorus (P) and base cations (K, Mg) corresponded to declines in remotely sensed mean annual canopy greenness (r2 = 0.77–0.85; p < 0.1), controlling for precipitation. The reason for this inverse relationship appears to be that litterfall also increased with increasing soil P and cation availability (r2 = 0.88–0.98; p < 0.1), resulting in a decline in greenness with increasing annual litterfall (r2 = 0.94; p < 0.1). As such, greater soil nutrient availability corresponded to greater leaf turnover, resulting in decreased greenness. However, these decreases in greenness with increasing soil P and cations were countered by increases in greenness with increasing soil nitrogen (N) (r2 = 0.14; p < 0.1), which had no significant relationship with litterfall, likely reflecting a direct effect of soil N on leaf chlorophyll content, but not on litterfall rates. In addition, greenness increased with extractable soil aluminum (Al) (r2 = 0.97; p < 0.1), but Al had no significant relationship with litterfall, suggesting a physiological adaptation of plants to high levels of toxic metals. Thus, spatial gradients in canopy greenness are not necessarily positive indicators of soil nutrient scarcity. Using a novel remote sensing index of canopy greenness limitation, we assessed how observed greenness compares with potential greenness. We found a strong relationship with soil N only (r2 = 0.65; p < 0.1), suggesting that tropical canopy greenness in Panama is predominantly limited by soil N, even if plant productivity (e.g., litterfall) responds to rock-derived nutrients. Moreover, greenness limitation was also significantly correlated with fine root biomass and soil carbon stocks (r2 = 0.62–0.71; p < 0.1), suggesting a feedback from soil N to canopy greenness to soil carbon storage. Overall, these data point to the potential utility of a remote sensing product for assessing belowground properties in tropical ecosystems.
Efficacy and safety of topical nitroglycerin in the prevention of mastectomy flap necrosis: a systematic review and meta-analysis
Authors: Wang Pu , Gu Luosha , Qin Zelian , Wang Qifei , Ma Jianxun
Published: April 2020

Flap necrosis is a common complication after mastectomy, and nitroglycerin (NTG) ointment has been used successfully to treat it. However, it is not clear whether topical NTG can completely prevent the occurrence of flap necrosis after breast cancer surgery, and it is also unclear whether this treatment may cause side effects. Three randomized controlled trials (RCTs) and two retrospective cohort studies (RCSs) were included in our investigation. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We found that NTG significantly reduced the rates of mastectomy flap necrosis, full-thickness flap necrosis, and debridement as well as the rate of early complications other than flap necrosis. However, there was no significant difference in drug-related adverse reactions, explantation, superficial flap necrosis, infection, hematoma or seroma between the NTG and placebo groups.