bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct neurostructural signatures of anxiety-, fear-related and depressive disorders: a comparative voxel-based meta-analysis
Authors: Liu Xiqin , Klugah-Brown Benjamin , Zhang Ran , Zhang Jie , Becker Benjamin 
Published: November 2021

AbstractInternalizing disorders encompass anxiety, fear and depressive disorders. While the DSM-5 nosology conceptualizes anxiety and fear-related disorders as an entity, dimensional psychopathology models suggest that generalized anxiety disorders (GAD) and major depression originate from an overarching “anxious-misery” factor whereas fear-related disorders originate from the “fear” factor. Given that a neurobiological evaluation is lacking, we conducted a comparative neuroimaging meta-analysis of gray matter volume alterations to determine common and disorder-specific brain structural signatures in these disorders. The PubMed, Web of Knowledge, and Scopus databases were searched for case-control voxel-based morphometric studies through December, 2020 in GAD, fear-related anxiety disorders (FAD, i.e., social anxiety disorders, SAD; specific phobias, SP; panic disorders, PD; and agoraphobia, AG) and major depressive disorder (MDD). Neurostructural abnormalities were assessed within each disorder group followed by quantitative comparison and conjunction analyses using Seed-based d-Mapping (SDM-PSI). GAD (9 studies, 226 patients) showed disorder-specific decreased volumes in left insula (z=-2.98, pFWE-corrected<0.05) and lateral/medial prefrontal cortex (z=-2.10, pFWE-corrected<0.05,) as well as increased right putamen volume (z=1.86, pFWE-corrected<0.05) relative to FAD (10 SAD, 11 PD, 2 SP studies, 918 patients). Both GAD and MDD (46 studies, 2,575 patients) exhibited decreased prefrontal volumes compared to controls and FAD. While FAD showed less robust alterations in lingual gyrus (p < 0.0025, uncorrected), this group presented intact frontal integrity. No shared structural abnormalities were found. Unique clinical features characterizing anxiety-, fear-related and depressive disorders are reflected by disorder-specific neuroanatomical abnormalities. Targeting the disorder-specific neurostructural signatures could improve therapeutic efficacy.
Violet light modulates the central nervous system to regulate memory and mood
Authors: Sasaki Nobunari , Gusain Pooja , Hayano Motoshi , Sugaya Tetsuro , Tonegawa Naoya , Hatanaka Yusuke , Tamura Risako , Okuyama Kei , Osada Hideto , Ban Norimitsu , Mitsukura Yasue , Lang Richard A. , Mimura Masaru , Tsubota Kazuo 
Published: November 2021

AbstractLight stimuli from the external environment serves as a signal. Photoreceptors receive photons at the outer nuclear layer of the retina. Non-visual photoreceptors, such as opsin5 (also known as OPN5 or neuropsin), are expressed in the retinal ganglion cells (RGCs) and hypothalamus to regulate the circadian cycle and body temperature. Here, we show that violet light (VL) stimuli received by OPN5-positive RGCs are transmitted to the habenula brain region. VL improves memory in aged mice and simultaneously increases neural architecture-related genes such as oligodendrocyte-related genes in the hippocampus. In addition, VL improves depressive-like behaviors in the social defeat stress model in an OPN5 dependent manner. Following VL exposure, cFos activation is observed at the nucleus accumbens (NAc) and the paraventricular thalamic nucleus (PVT). Taken together, the results indicate that violet light modulates brain function such as memory and mood by transmitting the signal from RGCs to the habenula region in the brain.
Conjugation of palbociclib with MHI-148 has an increased cytotoxic effect for breast cancer cells and an altered mechanism of action
Authors: Leung Euphemia , Tomek Petr , Tercel Moana , Reynisson Jóhannes , Park Thomas , Cooper Elizabeth , Denny William , Choi Peter , Jose Jiney 
Published: November 2021

AbstractThe CDK4/6 inhibitor palbociclib, combined with endocrine therapy, has been shown to be effective in postmenopausal women with estrogen receptor positive, HER2-negative advanced or metastatic breast cancer. However, palbociclib is not as effective in the highly aggressive triple-negative breast cancer that lacks sensitivity to chemotherapy or endocrine therapy. We hypothesized that conjugation of the near-infrared dye MHI-148 with palbociclib can produce a potential theranostic in triple-negative as well as estrogen receptor positive breast cancer cells. In our study, the conjugate was found to have enhanced activity in all mammalian cell lines tested in vitro. However, the conjugate was cytotoxic and did not induce G1 cell cycle arrest in breast cancer cells suggesting the mechanism of action differed from the parent compound palbociclib. The study highlights the importance of investigating the mechanism of conjugates of near-infrared dyes to therapeutic compounds as conjugation can potentially result in a change of mechanism or target, with an enhanced cytotoxic effect in this case.
A life cycle alteration can correct molting defects in Caenorhabditis elegans
Authors: Binti Shaonil , Melinda Rosa V. , Joseph Braveen B. , Edeen Phil , Miller Sam D. , Fay David S. 
Published: November 2021

AbstractMolting is a widespread feature in the development of many invertebrates, including nematodes and arthropods. In Caenorhabditis elegans, the highly conserved protein kinases NEKL-2/NEK8/9 and NEKL-3/NEK6/7 (NEKLs) promote molting through their involvement in the uptake and intracellular trafficking of epidermal cargos. We found that the relative requirements for NEKL-2 and NEKL-3 differed at different life-cycle stages and under different environmental conditions. Most notably, the transition from the second to the third larval stage (L2→L3 molt) required a higher level of NEKL function than during several other life stages or when animals had experienced starvation at the L1 stage. Specifically, larvae that entered the pre-dauer L2d stage could escape molting defects when transiting to the (non-dauer) L3 stage. Consistent with this, mutations that promote entry into L2d suppressed nekl-associated molting defects, whereas mutations that inhibit L2d entry reduced starvation-mediated suppression. We further showed that loss or reduction of NEKL functions led to defects in the transcription of cyclically expressed molting genes, many of which are under the control of systemic steroid hormone regulation. Moreover, the timing and severity of these transcriptional defects correlated closely with the strength of nekl alleles and with their stage of arrest. Interestingly, transit through L2d rescued nekl-associated expression defects in suppressed worms, providing an example of how life-cycle decisions can impact subsequent developmental events. Given that NEKLs are implicated in the uptake of sterols by the epidermis, we propose that loss of NEKLs leads to a physiological reduction in steroid-hormone signaling and consequent defects in the transcription of genes required for molting.
An interolog-based barley interactome as an integration framework for immune signaling
Authors: Velásquez-Zapata Valeria , Elmore J. Mitch , Fuerst Greg , Wise Roger P. 
Published: November 2021

ABSTRACTThe barley MLA nucleotide-binding, leucine-rich-repeat (NLR) receptor and its orthologs confer recognition specificity to many cereal diseases, including powdery mildew, stem and stripe rust, Victoria blight, and rice blast. We used interolog inference to construct a barley protein interactome (HvInt) comprising 66133 edges and 7181 nodes, as a foundation to explore signaling networks associated with MLA. HvInt was compared to the experimentally validated Arabidopsis interactome of 11253 proteins and 73960 interactions, verifying that the two networks share scale-free properties, including a power-law distribution and small-world network. Then, by successive layering of defense-specific ‘omics’ datasets, HvInt was customized to model cellular response to powdery mildew infection. Integration of HvInt with expression quantitative trait loci (eQTL) enabled us to infer disease modules and responses associated with fungal penetration and haustorial development. Next, using HvInt and an infection-time-course transcriptome, we assembled resistant (R) and susceptible (S) subnetworks. The resulting differentially co-expressed (R-S) interactome is essential to barley immunity, facilitates the flow of signaling pathways and is linked toMlathrough trans eQTL associations. Lastly, next-generation, yeast-two-hybrid screens identified fifteen novel MLA interactors, which were incorporated into HvInt, to predict receptor localization, and signaling response. These results link genomic, transcriptomic, and physical interactions during MLA-specified immunity.AUTHOR SUMMARYPowdery mildew fungi infect more than 9,500 agronomic and horticultural plant species. In order to prevent economic loss due to diseases caused by pathogens, plant breeders incorporate resistance genes into varieties that are grown for food, feed, fuel and fiber. One of these resistance genes encodes the barley MLA immune receptor, an ancestral cereal protein that confers recognition to powdery mildew, stem and stripe rust, rice blast and Victoria blight. However, in order to function properly, these immune receptors must interact with additional proteins and protein complexes during the different stages of fungal infection and plant defense. We used a combination of computational- and laboratory-based methods to predict over 66,000 possible protein-protein interactions in barley. This network of proteins was then integrated with various defense-specific datasets to assemble the molecular building blocks associated with resistance to the powdery mildew pathogen, in addition to those proteins that interact with the MLA immune receptor. Our application of genome-scale, protein-protein interaction data provides a foundation to decipher the complex molecular components that control immune responses in crops.
Laser-driven Wireless Deep Brain Stimulation using Temporal Interference and Organic Electrolytic Photocapacitors
Authors: Missey Florian , Donahue Mary J. , Weber Pascal , Ngom Ibrahima , Acerbo Emma , Botzanowski Boris , Migliaccio Ludovico , Jirsa Viktor , Głowacki Eric Daniel , Williamson Adam 
Published: November 2021

ABSTRACTDeep brain stimulation (DBS) is a technique commonly used both in clinical and fundamental neurosciences. Classically, brain stimulation requires an implanted and wired electrode system to deliver stimulation directly to the target area. Although techniques such as temporal interference (TI) can provide stimulation at depth without involving any implanted electrodes, these methods still rely on a wired apparatus which limits free movement. Herein we report organic photocapacitors as untethered light-driven electrodes which convert deep-red light into electric current. Pairs of these ultrathin devices can be driven using lasers at two different frequencies to deliver stimulation at depth via temporally interfering fields. We validate this concept of laser TI stimulation using numerical modeling, ex vivo tests with phantom samples, and finally in vivo tests. Wireless organic photocapacitors are placed on the cortex and elicit stimulation in the hippocampus, while not delivering off-target stimulation in the cortex. This laser-driven wireless TI evoked a neuronal response at depth that is comparable to control experiments induced with deep brain stimulation protocols using implanted electrodes. Our work shows that a combination of these two techniques – temporal interference and organic electrolytic photocapacitors – provides a reliable way to target brain structures requiring neither deeply implanted electrodes nor tethered stimulator devices. The laser TI protocol demonstrated here address two of the most important drawbacks in the field of deep brain stimulation and thus holds potential to solve many issues in freely-moving animal experiments or for clinical chronic therapy application.
A deeper cascade of mechanisms involved in cold resistance inHevea brasiliensis
Authors: Silva Carla Cristina Da , Bajay Stephanie Karenina , Aono Alexandre Hild , Francisco Felipe Roberto , Junior Ramir Bavaresco , Mantello Camila Campos , de Souza Anete Pereira , Vicentini dos Santos Renato 
Published: November 2021

AbstractBackgroundHevea brasiliensisis the main global source of natural rubber. Due to fungal disease pressure in hot, humid regions, rubber plantations have been moved to drier “escape areas” with lower temperatures. In order to analyze gene expression regulation during cold exposure, we studied young GT1 and RRIM 600 rubber tree clones with different cold tolerance strategies.ResultsAlongside traditional differential expression approaches, an RNA-seq gene coexpression network (GCN) was developed with 27,220 genes grouped into 205 gene clusters. The GCN related most rubber tree cold stress molecular responses to 31 clusters across three GCN modules: a downregulated group with 16 clusters and two upregulated groups with twelve and three clusters. The hub genes of the cold-responsive modules were also identified and analyzed. We observed that the general response to short-term cold exposure involves complex regulation of the jasmonic acid (JA) stress response and programmed cell death (PCD), upregulation of ethylene-responsive genes, and relaxation of florigen gene inhibition. As a result, we identified single DEGs and gained insights into the mechanisms involved in the response to cold stress in young rubber trees.ConclusionsOur findings may represent the species’ genetic stress responses developed during the course of evolution, since the examined varieties were genotypes selected during the early years of rubber tree domestication. Understanding the cold response mechanisms inH. brasiliensiscould improve breeding strategies for this crop, which has a narrow genetic base, is being impacted by climate change and is the only source for large-scale rubber production.
Different structures and pathologies of α-synuclein fibrils derived from preclinical and postmortem patients of Parkinson’s disease
Authors: Fan Yun , Sun Yunpeng , Yu Wenbo , Tao Youqi , Xia Wencheng , Liu Yiqi , Tang Yilin , Sun Yimin , Liu Fengtao , Cao Qin , Wu Jianjun , Liu Cong , Wang Jian , Li Dan 
Published: November 2021

Abstractα-Synuclein (α-syn) fibrillar aggregates are the major component of Lewy bodies and Lewy neurites presenting as the pathology hallmark of Parkinson’s disease (PD). Studies have shown that α-syn is potential to form different conformational fibrils associated with different synucleinopathies, but whether the conformation of α-syn fibrils changes in different phases of related diseases is to be explored. Here, we amplified α-syn aggregates from the cerebrospinal fluid (CSF) of preclinical (pre-PD) and late-stage postmortem PD (post-PD) patients. Our results show that compared to the CSF of pre-PD, that of post-PD is markedly stronger in seeding in vitro α-syn aggregation, and the amplified fibrils are more potent in inducing endogenous α-syn aggregation in neurons. Cryo-electron microscopic structures further reveal that the difference between the pre-PD- and post-PD-derived fibrils lies on a minor polymorph which in the pre-PD fibrils is morphologically straight, while in the post-PD fibrils represents a single protofilament assembled by a distinctive conformation of α-syn. Our work demonstrates structural and pathological differences between pre-PD and post-PD α-syn aggregation and suggests potential alteration of α-syn fibrils during the progression of PD clinical phases.Significance StatementIncreasing evidence support different conformational α-syn fibrils in patients with different α-synucleinopathies, but whether the conformation of α-syn fibrils changes in different phases of related diseases is unknown. Here, we show that α-syn fibrils amplified from the cerebrospinal fluid (CSF) of the late-stage postmortem PD (post-PD) patient are more potent in inducing endogenous α-syn aggregation in neurons than that amplified from the preclinical (pre-PD) patient. Cryo-EM structures further reveal that the post-PD fibrils contain a novel conformation that is distinct from either the pre-PD fibrils or those previously reported. Our work suggests conformational evolution of α-syn fibrils along with PD progression.
Cerebello-thalamic activity drives an abnormal motor network into dystonic tremor
Authors: Nieuwhof Freek , Toni Ivan , Dirkx Michiel F. , Gallea Cecile , Vidailhet Marie , Buijink Arthur W.G. , van Rootselaar Anne-Fleur , van de Warrenburg Bart P.C. , Helmich Rick C. 
Published: November 2021

AbstractDystonic tremor syndromes are highly burdensome and treatment is often inadequate. This is partly due to poor understanding of the underlying pathophysiology. Several lines of research suggest involvement of the cerebello-thalamo-cortical circuit and the basal ganglia in dystonic tremor syndromes, but their role is unclear. Here we aimed to investigate the contribution of the cerebello-thalamo-cortical circuit and the basal ganglia to the pathophysiology of dystonic tremor syndrome, by directly linking tremor fluctuations to cerebral activity during scanning. In 27 patients with dystonic tremor syndrome (dystonic tremor: n=23; tremor associated with dystonia: n=4), we used concurrent accelerometery and functional MRI during a posture holding task that evoked tremor, alternated with rest. Using multiple regression analyses, we separated tremor-related activity from brain activity related to (voluntary) posture holding. Using dynamic causal modelling, we tested for altered effective connectivity between tremor-related brain regions as a function of tremor amplitude fluctuations. Finally, we compared grey matter volume between patients (n=27) and matched controls (n=27).We found tremor-related activity in sensorimotor regions of the bilateral cerebellum, contralateral ventral intermediate (VIM) and ventro-oralis posterior nuclei (VOp) of the thalamus, contralateral primary motor cortex (hand area), contralateral pallidum, and the bilateral frontal cortex (laterality with respect to the tremor). Grey matter volume was increased in patients compared to controls in the portion of contralateral thalamus also showing tremor-related activity, as well as in bilateral medial and left lateral primary motor cortex, where no tremor-related activity was present. Effective connectivity analyses showed that inter-regional coupling in the cerebello-thalamic pathway, as well as the thalamic self-connection, were strengthened as a function of increasing tremor power.These findings indicate that the pathophysiology of dystonic tremor syndromes involves functional and structural changes in the cerebello-thalamo-cortical circuit and pallidum. Deficient input from the cerebellum towards the thalamo-cortical circuit, together with hypertrophy of the thalamus, may play a key role in the generation of dystonic tremor syndrome.
Spatialized Epidemiological Forecasting applied to Covid-19 Pandemic at Departmental Scale in France
Authors: Oliver Matthieu , Georges Didier , Prieur Clémentine 
Published: November 2021

AbstractIn this paper, we present a spatialized extension of a SIR model that accounts for undetected infections and recoveries as well as the load on hospital services. The spatialized compartmental model we introduce is governed by a set of partial differential equations (PDEs) defined on a spatial domain with complex boundary. We propose to solve the set of PDEs defining our model by using a meshless numerical method based on a finite difference scheme in which the spatial operators are approximated by using radial basis functions. Such an approach is reputed as flexible for solving problems on complex domains. Then we calibrate our model on the French department of Isère during the first period of lockdown, using daily reports of hospital occupancy in France. Our methodology allows to simulate the spread of Covid-19 pandemic at a departmental level, and for each compartment. However, the simulation cost prevents from online short-term forecast. Therefore, we propose to rely on reduced order modeling tools to compute short-term forecasts of infection number. The strategy consists in learning a time-dependent reduced order model with few compartments from a collection of evaluations of our spatialized detailed model, varying initial conditions and parameter values. A set of reduced bases is learnt in an offline phase while the projection on each reduced basis and the selection of the best projection is performed online, allowing short-term forecast of the global number of infected individuals in the department.
Comprehensive care programmes in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials and real-world studies
Authors: Yoo Daniel , Gong Mengqi , Meng Lei , Wong Cheuk Wai , Li Guangping , Sum Lam Michael Huen , Liu Tong , Tse Gary , Roever Leonardo ,   International Health Informatics Study (IHIS) Network
Published: November 2021

AbstractBackgroundDifferent comprehensive care programmes (CCPs) have been developed for patients with chronic obstructive pulmonary disorder (COPD), but data regarding their effectiveness have been controversial. PubMed and Embase were searched to 1st June 2017 for articles that investigated the effects of the different types of CCPs on hospitalization or mortality rates in COPD.ResultsA total of 67 studies including 3472633 patients (mean age: 76.1±12.7 years old; 41% male) were analyzed. CCPs reduced all-cause hospitalizations (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.63-0.79; P<0.001; I2:96%) and mortality (HR: 0.69, 95% CI: 0.573-0.83; P<0.001; I2:75%). Subgroup analyses for different CCP types were performed. Hospitalizations were reduced by pharmacist-led medication reviews (HR: 0.54; 95% CI: 0.37-0.78; P=0.001; I2:49%), structured care programmes (HR: 0.76; 95% CI: 0.66-0.87; P<0.0001; I2:88%) and self-management programmes (HR: 0.79; 95% CI: 0.64-0.99; P<0.05; I2:78%), but not continuity of care programmes (HR: 0.70; 95% CI: 0.36-1.36; P=0.29; I2:100%), early support discharge or home care packages (HR: 0.97; 95% CI: 0.91-1.04; P=0.37; I2:0%) or telemonitoring (HR: 0.61; 95% CI: 0.32-1.18; P=0.14; I2:94%). Mortality was reduced by early support discharge or home care packages (HR: 0.49; 95% CI: 0.30-0.80; P<0.01; I2:72%), structured care programmes (HR: 0.69; 95% CI: 0.53-0.90; P<0.01; I2:61%) and telemonitoring (HR: 0.52; 95% CI: 0.31-0.89; P<0.05; I2:0%), but not self-management programmes (HR: 0.79; 95% CI: 0.64-0.99; P<0.05; I2:78%).ConclusionsComprehensive care programmes reduce hospitalization and mortality in COPD patients.