bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of post-traumatic stress disorder in pharmacological intervention outcomes for adults with bipolar disorder: a protocol for a systematic review and meta-analysis
Authors: Russell Samantha E. , Wrobel Anna L. , Skvarc David , Kavanagh Bianca E , Ashton Melanie M , Dean Olivia M. , Berk Michael , Turner Alyna 
Published: May 2022

AbstractBackgroundRecent data indicates high prevalence of post-traumatic stress disorder (PTSD) in bipolar disorder (BD). PTSD may play a role in poor treatment outcomes and quality of life for people with BD. Despite this, few studies have examined the pharmacological treatment interventions and outcomes for this comorbidity. This systematic review will bring together currently available evidence regarding the impact of comorbid PTSD on pharmacological treatment outcomes in adults with BD.MethodsA systematic search of Embase, MEDLINE Complete, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be conducted to identify randomised and non-randomised studies of pharmacological interventions for adults with diagnosed bipolar disorder and PTSD. Data will be screened and extracted by two independent reviewers. Literature will be searched from the creation of the databases until April 1 2021. Risk of bias will be assessed using the Newcastle-Ottawa Scale and the Cochrane Collaborations Risk of Bias tool. A meta-analysis will be conducted if sufficient evidence is identified in the systematic review. The meta-analysis will employ a random-effects model and be evaluated using the I2 statistic.DiscussionThis review and meta-analysis will be the first to systematically explore and integrate the available evidence on the impact of PTSD on pharmacological treatments and outcome in those with BD. The results and outcomes of this systematic review will provide directions for future research and be published in relevant scientific journals and presented at research conferences.Systematic review registrationThe protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020182540).
Bridging Structural MRI with Cognitive Function for Individual Level Classification of Early Psychosis via Deep Learning
Authors: Wen Yang , Zhou Chuan , Chen Leiting , Deng Yu , Cleusix Martine , Jenni Raoul , Conus Philippe , Do Kim Q. , Xin Lijing 
Published: May 2022

ABSTRACTRecent efforts have been made to apply machine learning and deep learning approaches to the automated classification of schizophrenia using structural magnetic resonance imaging (sMRI) at the individual level. However, these approaches are less accurate on early psychosis (EP) since there are mild structural brain changes at early stage. As cognitive impairments is one main feature in psychosis, in this study we apply a multi-task deep learning framework using sMRI with inclusion of cognitive assessment to facilitate the classification EP patients from healthy individuals. Unlike previous studies, we used sMRI as the direct input to perform EP classifications and cognitive estimations. The proposed model does not require time-consuming volumetric or surface based analysis and can provide additionally cognition predictions. Extensive experiments were conducted on a sMRI data set with a total of 77 subjects (38 EP patients and 39 healthy controls), and we achieved 74.9±4.3% five-fold cross-validated accuracy and an area under the curve of 71.1±4.1% on EP classification with the inclusion of cognitive estimations. We reveal the feasibility of automated cognitive estimation using sMRI by deep learning models, and also demonstrate the implicit adoption of cognitive measures as additional information to facilitate EP classifications from healthy controls.
Loss of mitochondrial Chchd10 or Chchd2 in zebrafish leads to an ALS-like phenotype and Complex I deficiency independent of the mt-ISR
Authors: Légaré Virginie Petel , Rampal Christian J. , Aaltonen Mari J. , Janer Alexandre , Zinman Lorne , Shoubridge Eric A. , Armstrong Gary A.B. 
Published: May 2022

AbstractMutations inCHCHD10andCHCHD2, coding for two paralogous mitochondrial proteins, have been identified in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTD), and Parkinson’s disease (PD). Here we investigated the biological roles of these proteins during vertebrate development using knockout (KO) models in zebrafish. We demonstrate that loss of either or both proteins leads to a motor impairment, reduced survival, and compromised neuromuscular junction (NMJ) integrity in larval zebrafish. Compensation by Chchd10 was observed in thechchd2-/-model, but not by Chchd2 in thechchd10-/-model. The assembly of mitochondrial respiratory chain Complex I was impaired inchchd10-/-andchchd2-/-zebrafish larvae, but unexpectedly not in the doublechchd10-/-&chchd2-/-model, suggesting that reduced mitochondrial Complex I cannot be solely responsible for the observed phenotypes, which are generally more severe in the double KO. Activation of the mitochondrial integrated stress response (mt-ISR) was only observed in the double KO model, possibly implicating this pathway in the recovery of the Complex I defect, and suggesting that Complex I assembly defect in our single KO is independent of the mt-ISR. Our results demonstrate that both proteins are required for normal vertebrate development, but their precise molecular function in the mitochondrial biology of motor neurons remains to be discovered.
Translational approach to increase phosphate accumulation in two plant species through perturbance of inositol pyrophosphates
Authors: Freed Catherine , Craige Branch , Cridland Caitlin , Donahue Janet , Williams Sarah Phoebe , Kim Jiwoo , Gillaspy Glenda 
Published: May 2022

ABSTRACTInorganic phosphate (Pi), while indispensable for all biological organisms and a major agricultural macronutrient, is an increasingly limited and nonrenewable resource. Recent studies demonstrate the importance of inositol pyrophosphates (PP-InsPs) in plant Pi signaling and homeostasis, however the extent to which PP-InsPs impact plant development is not well understood. We report that transgenic expression of the Saccharomyces cerevisiae enzyme Diadenosine and Diphosphoinositol Polyphosphate Phosphohydrolase (DDP1) in Arabidopsis thaliana and Thlaspi arvense (pennycress) provide a unique translational utility for Pi phytoremediation as well as unique germplasm and insight on the long-term impacts of reduced PP-InsPs. Transgenic DDP1 expression in Arabidopsis decreased PP-InsPs, impacted growth and development, and increased Pi accumulation leading to Pi toxicity. Analysis of Pi Starvation Response (PSR) marker genes indicated that the PSR is activated in DDP1 expressing plants. We assessed translational utility through transformation of pennycress, a spring annual cover crop with emerging importance as a biofuel crop, with a DDP1 transgene. Pennycress plants expressing DDP1 showed similar altered Pi accumulation phenotypes, suggesting that these plants could potentially serve to remove Pi from Pi-rich soils. Our study addresses the long-term impacts of PP-InsP reduction on plant growth, as well as establishing a starting material for a unique Pi reclaiming cover crop.SIGNIFICANCE STATEMENTA major challenge to food security is the phosphorus (P) crisis. A global P shortage is imminent based on the misuse of current resources and will be further aggravated by climate change and a lack of policy addressing sustainability. Our work addresses this crisis by investigating the sustained impact of altering inositol pyrophosphates to manipulate plant P accumulation, a strategy that could be used to remediate nutrient-polluted environments.
Perchlorate-Specific Proteomic Stress Responses of Debaryomyces hansenii Could Enable Microbial Survival in Martian Brines
Authors: Heinz Jacob , Doellinger Joerg , Maus Deborah , Schneider Andy , Lasch Peter , Grossart Hans-Peter , Schulze-Makuch Dirk 
Published: May 2022

AbstractIf life exists on Mars, it would face several challenges including the presence of perchlorates, which destabilize biomacromolecules by inducing chaotropic stress. However, little is known about perchlorate toxicity for microorganism on the cellular level. Here we present the first proteomic investigation on the perchlorate-specific stress responses of the halotolerant yeast Debaryomyces hansenii and compare these to generally known salt stress adaptations. We found that the responses to NaCl and NaClO4-induced stresses share many common metabolic features, e.g., signaling pathways, elevated energy metabolism, or osmolyte biosynthesis. However, several new perchlorate-specific stress responses could be identified, such as protein glycosylation and cell wall remodulations, presumably in order to stabilize protein structures and the cell envelope. These stress responses would also be relevant for life on Mars, which - given the environmental conditions - likely developed chaotropic defense strategies such as stabilized confirmations of biomacromolecules and the formation of cell clusters.
ATP induced conformational change of axonemal outer dynein arms studied by cryo-electron tomography
Authors: Zimmermann Noemi , Noga Akira , Obbineni Jagan Mohan , Ishikawa Takashi 
Published: May 2022

AbstractAxonemal dyneins in the outer dynein arm (ODA) generate force for ciliary beating. We analyzed three states of ODA during the power stroke cycle using in situ cryo-electron tomography, subtomogram averaging and classification. These states of force generation depict the pre-power stroke, post-power stroke conformations and an intermediate state. Comparison of these conformations to published in vitro atomic structures of cytoplasmic dynein, ODA and Shulin-ODA complex showed that the orientation and position of the dynein head and linker differs. Our analysis shows that all dynein linkers in the in the absence of ATP interact with AAA3/AAA4, indicating interaction to the adjacent B-tubule direct dynein orientation. For the pre-power stroke conformation, we found changes of the tail anchored on the A-tubule. We built pseudo-atomic models from high-resolution structures to generate a best fitting atomic model to the in-situ pre- and post-power stroke ODA, thereby showing that the Shulin-ODA display similar conformation as the active pre-power stroke ODA conformation in the axoneme.
Two Competing Guilds as a Core Microbiome Signature for Health Recovery
Authors: Wu Guojun , Xu Ting , Zhao Naisi , Lam Yan Y. , Ding Xiaoying , Wei Dongqin , Fan Jian , Shi Yajuan , Li Xiaofeng , Li Mi , Ji Shenjie , Wang Xuejiao , Fu Huaqing , Zhang Feng , Shi Yu , Zhang Chenhong , Peng Yongde , Zhao Liping 
Published: May 2022

Summary ParagraphOver eons of co-evolution, the gut microbiota has become an essential organ for humans1,2. However, it is unclear what core members and their ecological organization ensures the stable provision of this organ’s essential health-relevant functions to the host. With high quality metagenome-assembled genomes as network nodes, here we identified two competing guilds3of the most stably and highly connected bacteria that together correlate with a wide range of host health conditions. Genomes in these two guilds kept their ecological relationship unchanged despite experiencing profound abundance changes during a 3-month high fiber intervention and 1-year follow-up in patients with type 2 diabetes (T2DM). The genomes of one guild harbored more genes for plant polysaccharide degradation and butyrate production, while the other guild had more genes for virulence or antibiotic resistance. A Random Forest regression model showed that the abundance distributions of these genomes were associated with 41 out of 43 bio-clinical parameters in the study cohort. With these genomes as reference, Random Forest modeling successfully classified case and control of T2DM, atherosclerotic cardiovascular disease, liver cirrhosis, inflammatory bowel diseases, colorectal cancer, ankylosing spondylitis, schizophrenia, and Parkinson’s disease in 12 independent metagenomic datasets from 1,816 participants across ethnicity and geography. This core microbiome signature may serve as a common target for health recovery.
Seabird morphology determines operational wind speeds, tolerable maxima and responses to extremes
Authors: Nourani Elham , Safi Kamran , de Grissac Sophie , Anderson David J. , Cole Nik C. , Fell Adam , Grémillet David , Lempidakis Emmanouil , Lerma Miriam , McKee Jennifer L. , Pichegru Lorien , Provost Pascal , Rattenborg Niels C. , Ryan Peter G. , Santos Carlos D. , Schoombie Stefan , Tatayah Vikash , Weimerskirch Henri , Wikelski Martin , Shepard. Emily L. C. 
Published: May 2022

SummaryStorms can cause widespread seabird strandings and wrecking1,2,3,4,5, yet little is known about the maximum wind speeds that birds are able to tolerate or the conditions they avoid. We analyzed > 300,000 hours of tracking data from 18 seabird species, including flapping and soaring fliers, to assess how flight morphology affects wind selectivity, both at fine scales (hourly movement steps) and across the breeding season. We found no general preference or avoidance of particular wind speeds within foraging tracks. This suggests seabird flight morphology is adapted to a “wind niche”, with higher wing loading being selected for in windier environments. In support of this, wing loading was positively related to the median wind speeds on the breeding grounds, as well as the maximum wind speeds in which birds flew. Yet globally, the highest wind speeds occur in the tropics (in association with tropical cyclones) where birds are morphologically adapted to low median wind speeds. Tropical species must therefore show behavioral responses to extreme winds, including long-range avoidance of wind speeds that can be twice their operable maxima. In contrast, procellariiformes flew in almost all wind speeds they encountered at a seasonal scale. Despite this, we describe a small number of cases where albatrosses avoided strong winds at close-range, including by flying into the eye of the storm. Extreme winds appear to pose context- dependent risks to seabirds, and more information is needed on the factors that determine the hierarchy of risk, given the impact of global change on storm intensity6,7.
Inner hair cell synapse density influences auditory processing
Authors: Ji Lingchao , Borges Beatriz C. , Martel David T. , Wu Calvin , Liberman M. Charles , Shore Susan E. , Corfas Gabriel 
Published: May 2022

AbstractLoss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy), leads to an auditory neuropathy called hidden hearing loss (HHL) characterized by normal auditory thresholds but reduced amplitude of sound-evoked auditory potentials. It has been proposed that synaptopathy and HHL result in poor performance in challenging hearing tasks despite a normal audiogram. However, this has only been tested in animals after exposure to noise or ototoxic drugs, which can cause deficits beyond synaptopathy. Furthermore, the impact of supernumerary synapses on auditory processing has not been evaluated. Here, we studied mice in which IHC synapse counts were increased or decreased by altering neurotrophin 3 (Ntf3) expression in IHC supporting cells. As we previously showed, postnatal Ntf3 knockdown or overexpression reduces or increases, respectively, IHC synapse density and suprathreshold amplitude of sound-evoked auditory potentials without changing cochlear thresholds. We now show that IHC synapse density does not influence the magnitude of the acoustic startle reflex or its prepulse inhibition. In contrast, gap-prepulse inhibition, a behavioral test for auditory temporal processing, is reduced or enhanced according to Ntf3 expression levels. These results indicate that IHC synaptopathy causes temporal processing deficits predicted in HHL. Furthermore, the improvement in temporal acuity achieved by increasing Ntf3 expression and synapse density suggests a therapeutic strategy for improving hearing in noise for individuals with synaptopathy of various etiologies.
Insight into RNA-DNA primer length counting by human primosome
Authors: Baranovskiy Andrey G. , Lisova Alisa E. , Morstadt Lucia M. , Babayeva Nigar D. , Tahirov Tahir H. 
Published: May 2022

ABSTRACTThe human primosome, a four-subunit complex of primase and DNA polymerase alpha (Polα), synthesizes chimeric RNA-DNA primers for DNA polymerases delta and epsilon to initiate DNA replication on both chromosome strands. Despite recent structural insights into the action of its two catalytic centers, the mechanism of DNA synthesis termination is still unclear. Here we report results of functional and structural studies revealing how the human primosome counts RNA-DNA primer length and timely terminates DNA elongation. Using a single-turnover primer extension assay, we defined two factors that determine a mature primer length (~35-mer): 1) a tight interaction of the C-terminal domain of the DNA primase large subunit (p58C) with the primer 5’-end, and 2) flexible tethering of p58C and the DNA polymerase alpha catalytic core domain (p180core) to the primosome platform domain by extended linkers. The obtained data allows us to conclude that p58C is a key regulator of all steps of RNA-DNA primer synthesis. The above-described findings provide a notable insight into the mechanism of DNA synthesis termination by a eukaryotic primosome, an important process for ensuring successful primer handover to replication DNA polymerases and for maintaining genome integrity.
Deeply conserved super-enhancers maintain stem cell pluripotency in placental mammals
Authors: Zhang Juqing , Zhou Yaqi , Yue Wei , Zhu Zhenshuo , Wu Xiaolong , Yu Shuai , Shen Qiaoyan , Pan Qin , Xu Wenjing , Zhang Rui , Wu Xiaojie , Li Xinmei , Li Yayu , Li Yunxiang , Wang Yu , Peng Sha , Zhang Shiqiang , Lei Anmin , Ding Xinbao , Yang Fan , Chen Xingqi , Li Na , Liao Mingzhi , Wang Wei , Hua Jinlian 
Published: May 2022

AbstractDespite pluripotent stem cells sharing key transcription factors, their maintenance involves distinct genetic inputs. Emerging evidence suggests that super-enhancers (SEs) can function as master regulatory hubs to control cell identity and pluripotency in humans and mice. However, whether pluripotency-associated SEs share a deep evolutionary origin in mammals remains elusive. Here, we performed comprehensive comparative epigenomic and transcription factor binding analyses among pigs, humans, and mice to identify pluripotency-associated SEs. Like typical enhancers, SEs displayed rapid evolution in mammals. We showed that BRD4 is an essential and conserved activator for mammalian pluripotency-associated SEs. Comparative motif enrichment analysis revealed 30 shared transcription factor binding motifs among the three species. The majority of the transcriptional factors that bind to identified motifs are known regulators associated with pluripotency. Further, we discovered three pluripotency-associated SEs (SE-SOX2, SE-PIM1, and SE-FGFR1) which displayed deep conservation in placental mammals and are sufficient to drive reporter gene expression in a pluripotency-dependent manner. Disruption of these conserved SEs through the CRISPR/Cas9 approach severely impaired the proliferative potential and the ability to form undifferentiated colonies. Our study provides insights into the understanding of conserved regulatory mechanisms underlying the maintenance of pluripotency as well as species-specific modulation of the pluripotency-associated regulatory networks in mammals.Significance statementSuper-enhancers (SEs) hold stronger power than regular enhancers to direct gene expression in the regulation of stem cell pluripotency. To dissect how pluripotency-associated SEs have evolved in mammals, we performed a systematic comparison of SEs among pigs, humans, and mice. Our analysis allowed the identification of three pluripotency-associated SEs (SE-SOX2, SE-PIM1, and SE-FGFR1) that are highly conserved inPlacentalia(accounting for 94% of mammals) as well as many species-specific SEs. All three SEs were sufficient to direct pluripotency-dependent gene expression and disruption of each conserved SE caused the loss of stem cell pluripotency. Our work highlights a small number of highly conserved SEs essential for the maintenance of pluripotency.
Pallidin function in drosophila surface glia regulates sleep and is dependent on amino acid availability
Authors: Li Hui , Aboudhiaf Sami , Parrot Sandrine , Scote-Blachon Céline , Benetollo Claire , Lin Jian-Sheng , Seugnet Laurent 
Published: May 2022

AbstractThe Pallidin protein is a component of a multimeric complex named the Biogenesis of Lysosome-related Organelles Complex 1 (BLOC1) that regulates specific endosomal function and transmembrane protein trafficking in many different cell types. In the brain, defective BLOC1 function has been linked to schizophrenia, a neuropsychiatric disorder with highly prevalent sleep disruptions, and to impaired cognitive abilities in healthy subjects. In animal models, defective BLOC1 function also impairs behavior, memory, neurotransmission systems and metabolism. This growing body of experimental evidence suggest an involvement of BLOC1 in sleep/wake regulation. Here, we used Drosophila molecular genetics and conditional, cell-type specific knockdown strategy to address this question. We show that down-regulation of a central subunit of BLOC1, Pallidin, in the surface glia, the Drosophila equivalent of the blood brain barrier, is sufficient to reduce, fragment and delay nighttime sleep at the adult stage and in a circadian clock dependent manner. Other members of the BLOC1 complex appear to be involved in this surface glia-dependent sleep regulation. In agreement with a BLOC1 involvement in amino acid transport, down-regulation of the Large neutral Amino acid Transporter 1 (LAT1)-like transporters JhI-21 and minidiscs, phenocopy the down-regulation of pallidin. Similar results were obtained by inhibiting the TOR amino acid signaling pathway. Supplementing food with essential amino acids normalizes the sleep/wake phenotypes of pallidin and JhI-21 down-regulation. Furthermore, we identify a role for pallidin in the subcellular trafficking of JhI-21 in surface glial cells. Finally, we provide evidence that Pallidin function in surface glia is required for GABAergic neurons activation involved in promoting sleep. Taken together, these data identify a novel role for BLOC1 that, through LAT1-like transporters subcellular trafficking modulates essential amino acid availability and GABAergic sleep/wake regulation.