bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of photocarrier relaxation dynamics in two-dimensional semiconductors
Authors: Wang Yuhan , Nie Zhonghui , Wang Fengqiu 
Published: November 2020

AbstractDue to strong Coulomb interactions, two-dimensional (2D) semiconductors can support excitons with large binding energies and complex many-particle states. Their strong light-matter coupling and emerging excitonic phenomena make them potential candidates for next-generation optoelectronic and valleytronic devices. The relaxation dynamics of optically excited states are a key ingredient of excitonic physics and directly impact the quantum efficiency and operating bandwidth of most photonic devices. Here, we summarize recent efforts in probing and modulating the photocarrier relaxation dynamics in 2D semiconductors. We classify these results according to the relaxation pathways or mechanisms they are associated with. The approaches discussed include both tailoring sample properties, such as the defect distribution and band structure, and applying external stimuli such as electric fields and mechanical strain. Particular emphasis is placed on discussing how the unique features of 2D semiconductors, including enhanced Coulomb interactions, sensitivity to the surrounding environment, flexible van der Waals (vdW) heterostructure construction, and non-degenerate valley/spin index of 2D transition metal dichalcogenides (TMDs), manifest themselves during photocarrier relaxation and how they can be manipulated. The extensive physical mechanisms that can be used to modulate photocarrier relaxation dynamics are instrumental for understanding and utilizing excitonic states in 2D semiconductors.
Behavioral, neuroanatomical, and molecular correlates of resilience and susceptibility to maternal immune activation
Authors: Mueller Flavia S. , Scarborough Joseph , Schalbetter Sina M. , Richetto Juliet , Kim Eugene , Couch Amalie , Yee Yohan , Lerch Jason P. , Vernon Anthony C. , Weber-Stadlbauer Ulrike , Meyer Urs 
Published: November 2020

AbstractInfectious or noninfectious maternal immune activation (MIA) is an environmental risk factor for psychiatric and neurological disorders with neurodevelopmental etiologies. Whilst there is increasing evidence for significant health consequences, the effects of MIA on the offspring appear to be variable. Here, we aimed to identify and characterize subgroups of isogenic mouse offspring exposed to identical MIA, which was induced in C57BL6/N mice by administration of the viral mimetic, poly(I:C), on gestation day 12. Cluster analysis of behavioral data obtained from a first cohort containing >150 MIA and control offspring revealed that MIA offspring could be stratified into distinct subgroups that were characterized by the presence or absence of multiple behavioral dysfunctions. The two subgroups also differed in terms of their transcriptional profiles in cortical and subcortical brain regions and brain networks of structural covariance, as measured by ex vivo structural magnetic resonance imaging (MRI). In a second, independent cohort containing 50 MIA and control offspring, we identified a subgroup of MIA offspring that displayed elevated peripheral production of innate inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in adulthood. This subgroup also showed significant impairments in social approach behavior and sensorimotor gating, whereas MIA offspring with a low inflammatory cytokine status did not. Taken together, our results highlight the existence of subgroups of MIA-exposed offspring that show dissociable behavioral, transcriptional, brain network, and immunological profiles even under conditions of genetic homogeneity. These data have relevance for advancing our understanding of the variable neurodevelopmental effects induced by MIA and for biomarker-guided approaches in preclinical psychiatric research.
Maternal alcohol consumption and risk of offspring with congenital malformation: the Japan Environment and Children’s Study
Authors: Kurita Hiroshi , Motoki Noriko , Inaba Yuji , Misawa Yuka , Ohira Satoshi , Kanai Makoto , Tsukahara Teruomi , Nomiyama Tetsuo ,   the Japan Environment and Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko 
Published: November 2020

Abstract
Background
The association between fetal exposure to alcohol and congenital structural disorders remains inconclusive. The present study searched for relationships between maternal alcohol consumption during pregnancy and the risk of congenital malformations.

Methods
We evaluated the fixed dataset of a large national birth cohort study including 73,595 mothers with a singleton live birth. Information regarding the alcohol consumption of mothers was obtained from self-reported questionnaires. Physicians assessed for 6 major congenital malformations (congenital heart defects [CHDs], male genital abnormalities, limb defects, cleft lip and/or cleft palate [orofacial clefts (OFC)], severe brain abnormalities, and gastrointestinal obstructions) up to 1 month after birth. Multiple logistic regression analysis was performed to identify associations between maternal alcohol consumption during pregnancy and each malformation.

Results
The prevalence of maternal drinking in early pregnancy and until the second/third trimester was 46.6% and 2.8%, respectively. The onset of CHD was inversely associated with mothers who quit drinking during early pregnancy (OR 0.85, 95% CI 0.74–0.98). There was no remarkable impact of maternal drinking habit status on the other congenital malformations after adjustment for covariates.

Conclusions
Maternal alcohol consumption during pregnancy, even in early pregnancy, displayed no significant adverse impact on congenital malformations of interest.

Impact

This large-scale Japanese cohort study revealed that no teratogenic associations were found between maternal retrospective reports of periconceptional alcohol consumption and congenital malformations after adjustment for covariates.

This is the first nationwide birth cohort study in Japan to assess the effect of maternal alcohol consumption during pregnancy on major congenital malformations.

Our finding indicated that maternal low-to-moderate alcohol consumption during pregnancy, even in early pregnancy, displayed no significant adverse impact on congenital heart defects, male genital abnormalities, limb defects, orofacial clefts, severe brain abnormalities, or gastrointestinal obstructions.
Novel neuronal surface autoantibodies in plasma of patients with depression and anxiety
Authors: Zong Shenghua , Correia-Hoffmann Carolin , Mané-Damas Marina , Kappelmann Nils , Molenaar Peter C. , van Grootheest Gerard , Penninx Brenda W. J. H. , Rouhl Rob P. W. , Losen Mario , Martinez-Martinez Pilar 
Published: November 2020

AbstractNeuronal surface autoantibodies (NSAbs) against various antigens cause autoimmune encephalitis. Some of these antigens are also involved in the pathology of depression and anxiety. To study whether NSAbs are more common in plasma of individuals with depression and anxiety than in controls, and to investigate if NSAbs correlate with disease status, plasma samples of 819 individuals with a current diagnosis of depression and/or anxiety, 920 in remission and 492 individuals without these disorders were included in this study. Samples were tested by a combination of immunohistochemistry (IHC), staining on live rat hippocampus neurons and cell-based assay (CBA). By IHC, 50 (2.2%) samples showed immunoreactivity to rat brain tissue, with no significant differences between the aforementioned groups (22/819 vs 18/920 vs 11/492, P > 0.99). In addition, eight IHC positive samples were positive for NSAbs on live neurons (7/819 vs 0/920 vs 1/492, P = 0.006). The IHC-staining patterns of these eight samples were atypical for autoimmune encephalitis and accordingly, they tested negative for known NSAbs by CBA. No obvious difference in the clinical characteristics between individuals with or without NSAbs was observed. In conclusion, novel NSAbs were rare but predominately found in patients with current anxiety or depression indicating they might affect mental health in a small group of patients.
Cysteine metabolic circuitries: druggable targets in cancer
Authors: Bonifácio Vasco D. B. , Pereira Sofia A. , Serpa Jacinta , Vicente João B. 
Published: November 2020

AbstractTo enable survival in adverse conditions, cancer cells undergo global metabolic adaptations. The amino acid cysteine actively contributes to cancer metabolic remodelling on three different levels: first, in its free form, in redox control, as a component of the antioxidant glutathione or its involvement in protein s-cysteinylation, a reversible post-translational modification; second, as a substrate for the production of hydrogen sulphide (H2S), which feeds the mitochondrial electron transfer chain and mediates per-sulphidation of ATPase and glycolytic enzymes, thereby stimulating cellular bioenergetics; and, finally, as a carbon source for epigenetic regulation, biomass production and energy production. This review will provide a systematic portrayal of the role of cysteine in cancer biology as a source of carbon and sulphur atoms, the pivotal role of cysteine in different metabolic pathways and the importance of H2S as an energetic substrate and signalling molecule. The different pools of cysteine in the cell and within the body, and their putative use as prognostic cancer markers will be also addressed. Finally, we will discuss the pharmacological means and potential of targeting cysteine metabolism for the treatment of cancer.
The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer
Authors: Alexander Peter G. , Roseweir Antonia K. , Pennel Kathryn A. F. , van Wyk Hester C. , Powell Arfon G. M. T. , McMillan Donald C. , Horgan Paul G. , Kelly Caroline , Hay Jennifer , Sansom Owen , Harkin Andrea , Roxburgh Campbell S. D. , Graham Janet , Church David N. , Tomlinson Ian , Saunders Mark , Iveson Tim J. , Edwards Joanne , Park James H. 
Published: November 2020

Abstract
Background
The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy.

Methods
Two cohorts were utilised; 862 TNM I–III CRC validation cohort, and 2912 TNM II–III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction.

Results
GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85–5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39–3.41, p = 0.001). In TransSCOT, chemotherapy type (pinteraction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19–4.16, p = 0.012).

Conclusions
This study validates the GMS as a prognostic tool for patients with stage I–III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX.
Corticotropin-releasing hormone (CRH) alters mitochondrial morphology and function by activating the NF-kB-DRP1 axis in hippocampal neurons
Authors: Battaglia Chiara R. , Cursano Silvia , Calzia Enrico , Catanese Alberto , Boeckers Tobias M. 
Published: November 2020

AbstractNeuronal stress-adaptation combines multiple molecular responses. We have previously reported that thorax trauma induces a transient loss of hippocampal excitatory synapses mediated by the local release of the stress-related hormone corticotropin-releasing hormone (CRH). Since a physiological synaptic activity relies also on mitochondrial functionality, we investigated the direct involvement of mitochondria in the (mal)-adaptive changes induced by the activation of neuronal CRH receptors 1 (CRHR1). We observed, in vivo and in vitro, a significant shift of mitochondrial dynamics towards fission, which correlated with increased swollen mitochondria and aberrant cristae. These morphological changes, which are associated with increased NF-kB activity and nitric oxide concentrations, correlated with a pronounced reduction of mitochondrial activity. However, ATP availability was unaltered, suggesting that neurons maintain a physiological energy metabolism to preserve them from apoptosis under CRH exposure. Our findings demonstrate that stress-induced CRHR1 activation leads to strong, but reversible, modifications of mitochondrial dynamics and morphology. These alterations are accompanied by bioenergetic defects and the reduction of neuronal activity, which are linked to increased intracellular oxidative stress, and to the activation of the NF-kB/c-Abl/DRP1 axis.
The regulatory function of the AAA4 ATPase domain of cytoplasmic dynein
Authors: Liu Xinglei , Rao Lu , Gennerich Arne 
Published: November 2020

AbstractCytoplasmic dynein is the primary motor for microtubule minus-end-directed transport and is indispensable to eukaryotic cells. Although each motor domain of dynein contains three active AAA+ ATPases (AAA1, 3, and 4), only the functions of AAA1 and 3 are known. Here, we use single-molecule fluorescence and optical tweezers studies to elucidate the role of AAA4 in dynein’s mechanochemical cycle. We demonstrate that AAA4 controls the priming stroke of the motion-generating linker, which connects the dimerizing tail of the motor to the AAA+ ring. Before ATP binds to AAA4, dynein remains incapable of generating motion. However, when AAA4 is bound to ATP, the gating of AAA1 by AAA3 prevails and dynein motion can occur. Thus, AAA1, 3, and 4 work together to regulate dynein function. Our work elucidates an essential role for AAA4 in dynein’s stepping cycle and underscores the complexity and crosstalk among the motor’s multiple AAA+ domains.
Structure of the respiratory MBS complex reveals iron-sulfur cluster catalyzed sulfane sulfur reduction in ancient life
Authors: Yu Hongjun , Haja Dominik K. , Schut Gerrit J. , Wu Chang-Hao , Meng Xing , Zhao Gongpu , Li Huilin , Adams Michael W. W. 
Published: November 2020

AbstractModern day aerobic respiration in mitochondria involving complex I converts redox energy into chemical energy and likely evolved from a simple anaerobic system now represented by hydrogen gas-evolving hydrogenase (MBH) where protons are the terminal electron acceptor. Here we present the cryo-EM structure of an early ancestor in the evolution of complex I, the elemental sulfur (S0)-reducing reductase MBS. Three highly conserved protein loops linking cytoplasmic and membrane domains enable scalable energy conversion in all three complexes. MBS contains two proton pumps compared to one in MBH and likely conserves twice the energy. The structure also reveals evolutionary adaptations of MBH that enabled S0 reduction by MBS catalyzed by a site-differentiated iron-sulfur cluster without participation of protons or amino acid residues. This is the simplest mechanism proposed for reduction of inorganic or organic disulfides. It is of fundamental significance in the iron and sulfur-rich volcanic environments of early earth and possibly the origin of life. MBS provides a new perspective on the evolution of modern-day respiratory complexes and of catalysis by biological iron-sulfur clusters.
STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells
Authors: Jin Lin , Chen Yunjia , Crossman David K. , Datta Arunima , Vu Trung , Mobley James A. , Basu Malay Kumar , Scarduzio Mariangela , Wang Hengbin , Chang Chenbei , Datta Pran K. 
Published: November 2020

AbstractAlternative splicing (AS) is involved in cell fate decisions and embryonic development. However, regulation of these processes is poorly understood. Here, we have identified the serine threonine kinase receptor-associated protein (STRAP) as a putative spliceosome-associated factor. Upon Strap deletion, there are numerous AS events observed in mouse embryoid bodies (EBs) undergoing a neuroectoderm-like state. Global mapping of STRAP-RNA binding in mouse embryos by enhanced-CLIP sequencing (eCLIP-seq) reveals that STRAP preferably targets transcripts for nervous system development and regulates AS through preferred binding positions, as demonstrated for two neuronal-specific genes, Nnat and Mark3. We have found that STRAP involves in the assembly of 17S U2 snRNP proteins. Moreover, in Xenopus, loss of Strap leads to impeded lineage differentiation in embryos, delayed neural tube closure, and altered exon skipping. Collectively, our findings reveal a previously unknown function of STRAP in mediating the splicing networks of lineage commitment, alteration of which may be involved in early embryonic lethality in mice.
High-performance compliant thermoelectric generators with magnetically self-assembled soft heat conductors for self-powered wearable electronics
Authors: Lee Byeongmoon , Cho Hyeon , Park Kyung Tae , Kim Jin-Sang , Park Min , Kim Heesuk , Hong Yongtaek , Chung Seungjun 
Published: November 2020

AbstractSoftening of thermoelectric generators facilitates conformal contact with arbitrary-shaped heat sources, which offers an opportunity to realize self-powered wearable applications. However, existing wearable thermoelectric devices inevitably exhibit reduced thermoelectric conversion efficiency due to the parasitic heat loss in high-thermal-impedance polymer substrates and poor thermal contact arising from rigid interconnects. Here, we propose compliant thermoelectric generators with intrinsically stretchable interconnects and soft heat conductors that achieve high thermoelectric performance and unprecedented conformability simultaneously. The silver-nanowire-based soft electrodes interconnect bismuth-telluride-based thermoelectric legs, effectively absorbing strain energy, which allows our thermoelectric generators to conform perfectly to curved surfaces. Metal particles magnetically self-assembled in elastomeric substrates form soft heat conductors that significantly enhance the heat transfer to the thermoelectric legs, thereby maximizing energy conversion efficiency on three-dimensional heat sources. Moreover, automated additive manufacturing paves the way for realizing self-powered wearable applications comprising hundreds of thermoelectric legs with high customizability under ambient conditions.
Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia
Authors: An Furun , Wang Huiping , Liu Zhenyun , Wu Fan , Zhang Jiakui , Tao Qianshan , Li Yingwei , Shen Yuanyuan , Ruan Yanjie , Zhang Qing , Pan Ying , Zhu Weiwei , Qin Hui , Wang Yansheng , Fu Yongling , Feng Zhenqing , Zhai Zhimin 
Published: November 2020

AbstractCD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.
Controlling bimerons as skyrmion analogues by ferroelectric polarization in 2D van der Waals multiferroic heterostructures
Authors: Sun Wei , Wang Wenxuan , Li Hang , Zhang Guangbiao , Chen Dong , Wang Jianli , Cheng Zhenxiang 
Published: November 2020

AbstractAtom-thick van der Waals heterostructures with nontrivial physical properties tunable via the magnetoelectric coupling effect are highly desirable for the future advance of multiferroic devices. In this work on LaCl/In2Se3 heterostructure consisting of a 2D ferromagnetic layer and a 2D ferroelectric layer, reversible switch of the easy axis and the Curie temperature of the magnetic LaCl layer has been enabled by switching of ferroelectric polarization in In2Se3. More importantly, magnetic skyrmions in the bimerons form have been discovered in the LaCl/In2Se3 heterostructure and can be driven by an electric current. The creation and annihilation of bimerons in LaCl magnetic nanodisks were achieved by polarization switching. It thus proves to be a feasible approach to achieve purely electric control of skyrmions in 2D van der Waals heterostructures. Such nonvolatile and tunable magnetic skyrmions are promising candidates for information carriers in future data storage and logic devices operated under small electrical currents.
TDP-43 interacts with amyloid-β, inhibits fibrillization, and worsens pathology in a model of Alzheimer’s disease
Authors: Shih Yao-Hsiang , Tu Ling-Hsien , Chang Ting-Yu , Ganesan Kiruthika , Chang Wei-Wei , Chang Pao-Sheng , Fang Yu-Sheng , Lin Yeh-Tung , Jin Lee-Way , Chen Yun-Ru 
Published: November 2020

AbstractTDP-43 inclusions are found in many Alzheimer’s disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ’s ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.