bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shock Compression of Fluorapatite to 120 GPa
Authors: Rucks M. J. , Winey J. M. , Toyoda Y. , Gupta Y. M. , Duffy T. S. 
Published: January 2023

AbstractApatite is a phosphate mineral relevant to shock metamorphism in planetary materials. Here, we report on the response of natural fluorapatite from Durango, Mexico, under shock wave loading between 14.5 and 119.5 GPa. Wave profile measurements were obtained in plate‐impact experiments conducted on [0001]‐oriented fluorapatite single crystals. To 30 GPa peak stresses, we observed a two‐wave structure indicating an elastic‐inelastic response with elastic wave amplitudes of 10.5–13.1 GPa. Between 39.1 and 62.1 GPa, a complex wave structure was observed involving the propagation of three waves. At and above 73.7 GPa, only a single shock wave was observed. The data above 73.7 GPa provided the following linear shock velocity—particle velocity relationship: Us = 6.5(2) + 0.78(6) up, (mm/μs). Above 80 GPa, the densities in the shocked state exceed both the extrapolated 300‐K density of fluorapatite and the predicted 300‐K density for a mixture of the high‐pressure assemblage, tuite, and CaF2. This result indicates that fluorapatite undergoes a transition to a denser structure under shock loading at these conditions. The shock response of fluorapatite is observed to be similar to that of enstatite but stiffer than quartz and albite at the stresses examined in this work.
RCS Diagnostic Imaging Using Parameter Extraction Technique of State Space Method
Authors: Huang Jinhai , Liu Xumin , Zhou Jianjiang , Deng Yao 
Published: January 2023

AbstractThe signature extraction and processing are the key aspects of enhancing recognition ability for radar target characteristics. In this paper, to reveal the intrinsic property of the target and improve the accuracy of radar cross section (RCS), we proposed RCS diagnostic imaging technique, extracting the parameters of scattering center model by state space method (SSM), to analyze the signature of GTD‐based returns. To demonstrate the effectiveness of SSM, the comparison with estimating signal parameter via rotational invariance techniques method by the analysis of goodness‐of‐fit and root mean square error, reconstructing the RCS profile through original signal model, and employing SSM to extract the signature of specular and creeping wave from the PEC sphere. Furthermore, the RCS diagnostic imaging by SSM extracting position and amplitude is discussed, and range‐isolated pole technique specific to the creeping wave extraction is addressed the advantage of SSM.
Obesity and adverse childhood experiences in relation to stress during the COVID-19 pandemic: an analysis of the Canadian Longitudinal Study on Aging
Authors: De Rubeis Vanessa , Gonzalez Andrea , de Groh Margaret , Jiang Ying , Erbas Oz Urun , Tarride Jean-Eric , Basta Nicole E. , Kirkland Susan , Wolfson Christina , Griffith Lauren E. , Raina Parminder , Anderson Laura N. ,   the Canadian Longitudinal Study on Aging (CLSA) Team, Costa Andrew , Balion Cynthia , Asada Yukiko , Cossette Benoȋt , Levasseur Melanie , Hofer Scott , Paterson Theone , Hogan David , McMillan Jacqueline , Liu-Ambrose Teresa , Menec Verena , St. John Philip , Mugford Gerald , Gao Zhiwei , Taler Vanessa , Davidson Patrick , Wister Andrew , Cosco Theodore 
Published: January 2023

Abstract
Background
People with obesity are at increased risk of chronic stress, and this may have been exacerbated during the COVID-19 pandemic. Adverse childhood experiences (ACE) are also associated with both obesity and stress, and may modify risk of stress among people with obesity. The objectives of this study were to evaluate the associations between obesity, ACEs, and stress during the pandemic, and to determine if the association between obesity and stress was modified by ACEs.

Methods
A longitudinal study was conducted among adults aged 50–96 years (n = 23,972) from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Study. Obesity and ACEs were collected pre-pandemic (2015–2018), and stress was measured at COVID-19 Exit Survey (Sept-Dec 2020). We used logistic, Poisson, and negative binomial regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the associations between obesity, ACEs, and stress outcomes during the pandemic. Interaction by ACEs was evaluated on the additive and multiplicative scales.

Results
People with obesity were more likely to experience an increase in overall stressors (class III obesity vs. healthy weight RR = 1.19; 95% CI: 1.12–1.27) as well as increased health related stressors (class III obesity vs. healthy weight RR: 1.25; 95% CI: 1.12–1.39) but did not perceive the consequences of the pandemic as negative. ACEs were also associated an increase in overall stressors (4–8 ACEs vs. none RR = 1.38; 95% CI: 1.33–1.44) and being more likely to perceive the pandemic as negative (4–8 ACEs vs. none RR = 1.32; 95% CI: 1.19–1.47). The association between obesity and stress was not modified by ACEs.

Conclusions
Increased stress during the first year of the COVID-19 pandemic was observed among people with obesity or ACEs. The long-term outcomes of stress during the pandemic need to be determined.
Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment
Authors: McCutcheon Robert A. , Keefe Richard S. E. , McGuire Philip K. 
Published: January 2023

AbstractCognitive deficits are a core feature of schizophrenia, account for much of the impaired functioning associated with the disorder and are not responsive to existing treatments. In this review, we first describe the clinical presentation and natural history of these deficits. We then consider aetiological factors, highlighting how a range of similar genetic and environmental factors are associated with both cognitive function and schizophrenia. We then review the pathophysiological mechanisms thought to underlie cognitive symptoms, including the role of dopamine, cholinergic signalling and the balance between GABAergic interneurons and glutamatergic pyramidal cells. Finally, we review the clinical management of cognitive impairments and candidate novel treatments.
Divergent projections of the prelimbic cortex mediate autism- and anxiety-like behaviors
Authors: Luo Yi-Fan , Lu Lu , Song Heng-Yi , Xu Han , Zheng Zhi-Wei , Wu Zhou-Yue , Jiang Chen-Chen , Tong Chu , Yuan Hao-Yang , Liu Xiu-Xiu , Chen Xiang , Sun Mei-ling , Tang Ya-Min , Fan Heng-Yu , Han Feng , Lu Ying-Mei 
Published: January 2023

AbstractThe comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74-/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PLPNs–dSTRFSIs) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PLPNs–BLAPNs) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL–dSTR or PL–BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL–dSTR and PL–BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity.
Does treatment with autophagy-enhancers and/or ROS-scavengers alleviate behavioral and neurochemical consequences of low-dose rotenone-induced mild mitochondrial dysfunction in mice?
Authors: Damri O. , Natour S. , Asslih S. , Agam G. 
Published: January 2023

AbstractBipolar-disorder’s pathophysiology and the mechanism by which medications exert their beneficial effect is yet unknown, but others’ and our data implicate patients’ brain mitochondrial-dysfunction and its amendment by mood-stabilizers. We recently designed a novel mouse bipolar-disorder-like model using chronic administration of a low-dose of the oxidative-phosphorylation complex I inhibitor, rotenone. Four and eight weeks rotenone treatment induced manic- and depressive-like behavior, respectively, accompanied by mood-related neurochemical changes. Here we aimed to investigate whether each of the autophagy-enhancers lithium (a mood-stabilizer), trehalose and resveratrol and/or each of the reactive oxygen species (ROS)-scavengers, resveratrol and N-acetylcystein and/or the combinations lithium+resveratrol or trehalose+N-acetylcystein, can ameliorate behavioral and neurochemical consequences of neuronal mild mitochondrial-dysfunction. We observed that lithium, trehalose and N-acetylcystein reversed rotenone-induced manic-like behavior as well as deviations in protein levels of mitochondrial complexes and the autophagy marker LC3-II. This raises the possibility that mild mitochondrial-dysfunction accompanied by impaired autophagy and a very mild increase in ROS levels are related to predisposition to manic-like behavior. On the other hand, although, as expected, most of the drugs tested eliminated the eight weeks rotenone-induced increase in protein levels of all hippocampal mitochondrial complexes, only lithium ubiquitously ameliorated the depressive-like behaviors. We cautiously deduce that aberrant autophagy and/or elevated ROS levels are not involved in predisposition to the depressive phase of bipolar-like behavior. Rather, that amending the depressive–like characteristics requires different mitochondria-related interventions. The latter might be antagonizing N-methyl-D-aspartate receptors (NMDARs), thus protecting from disruption of mitochondrial calcium homeostasis and its detrimental consequences. In conclusion, our findings suggest that by-and-large, among the autophagy-enhancers and ROS-scavengers tested, lithium is the most effective in counteracting rotenone-induced changes. Trehalose and N-acetylcystein may also be effective in attenuating manic-like behavior.
Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study
Authors: Langley Christelle , Armand Sophia , Luo Qiang , Savulich George , Segerberg Tina , Søndergaard Anna , Pedersen Elisabeth B. , Svart Nanna , Overgaard-Hansen Oliver , Johansen Annette , Borgsted Camilla , Cardinal Rudolf N. , Robbins Trevor W. , Stenbæk Dea S. , Knudsen Gitte M. , Sahakian Barbara J. 
Published: January 2023

AbstractSeveral studies of the effects on cognition of selective serotonin reuptake inhibitors (SSRI), administered either acutely or sub-chronically in healthy volunteers, have found changes in learning and reinforcement outcomes. In contrast, to our knowledge, there have been no studies of chronic effects of escitalopram on cognition in healthy volunteers. This is important in view of its clinical use in major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). Consequently, we aimed to investigate the chronic effect of the SSRI, escitalopram, on measures of ‘cold’ cognition (including inhibition, cognitive flexibility, memory) and ‘hot cognition’ including decision-making and particularly reinforcement learning. The study, conducted at the University of Copenhagen between May 2020 and October 2021, used a double-blind placebo-controlled design with 66 healthy volunteers, semi-randomised to receive either 20 mg of escitalopram (n = 32) or placebo (n = 34), balanced for age, sex and intelligence quotient (IQ) for at least 21 days. Questionnaires, neuropsychological tests and serum escitalopram measures were taken. We analysed group differences on the cognitive measures using linear regression models as well as innovative hierarchical Bayesian modelling of the Probabilistic Reversal Learning (PRL) task. The novel and important finding was that escitalopram reduced reinforcement sensitivity compared to placebo on both the Sequential Model-Based/Model-Free task and the PRL task. We found no other significant group differences on ‘cold’ or ‘hot’ cognition. These findings demonstrate that serotonin reuptake inhibition is involved in reinforcement learning in healthy individuals. Lower reinforcement sensitivity in response to chronic SSRI administration may reflect the ‘blunting’ effect often reported by patients with MDD treated with SSRIs. Trial Registration:NCT04239339.
PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation
Authors: Liu Bo , Yao Xueting , Zhang Chaoyang , Liu Yufen , Wei Li , Huang Qinying , Wang Mengting , Zhang Yanchen , Hu Danning , Wu Wencan 
Published: January 2023

AbstractAutophagy dysfunction is one of the common causes of tumor formation and plays an important role in uveal melanoma (UM). However, little is known about the regulatory mechanisms of autophagy in UM. Here, we show that PTK6 can promote the proliferation, migration, and invasion of UM cells by inhibiting autophagy. SOCS3 can inhibit the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 can partially rescue the PTK6-induced promotion of UM cell proliferation, migration, and invasion. Mechanistically, PTK6 can bind to SOCS3, and SOCS3 can downregulate the expression of PTK6. Furthermore, PTK6 can upregulate the phosphorylation of mTOR to inhibit autophagy. Taken together, our findings demonstrate the functions of PTK6 and SOCS3 in UM cells and targeting the SOCS3-PTK6 signaling axis might be a novel and promising therapeutic strategy for patients with UM.
Small heat shock proteins operate as molecular chaperones in the mitochondrial intermembrane space
Authors: Adriaenssens Elias , Asselbergh Bob , Rivera-Mejías Pablo , Bervoets Sven , Vendredy Leen , De Winter Vicky , Spaas Katrien , de Rycke Riet , van Isterdael Gert , Impens Francis , Langer Thomas , Timmerman Vincent 
Published: January 2023

AbstractMitochondria are complex organelles with different compartments, each harbouring their own protein quality control factors. While chaperones of the mitochondrial matrix are well characterized, it is poorly understood which chaperones protect the mitochondrial intermembrane space. Here we show that cytosolic small heat shock proteins are imported under basal conditions into the mitochondrial intermembrane space, where they operate as molecular chaperones. Protein misfolding in the mitochondrial intermembrane space leads to increased recruitment of small heat shock proteins. Depletion of small heat shock proteins leads to mitochondrial swelling and reduced respiration, while aggregation of aggregation-prone substrates is countered in their presence. Charcot–Marie–Tooth disease-causing mutations disturb the mitochondrial function of HSPB1, potentially linking previously observed mitochondrial dysfunction in Charcot–Marie–Tooth type 2F to its role in the mitochondrial intermembrane space. Our results reveal that small heat shock proteins form a chaperone system that operates in the mitochondrial intermembrane space.
Using high-frequency household surveys to describe energy use in rural North India during the COVID-19 pandemic
Authors: Gould Carlos F. , Pillarisetti Ajay , Thompson Lisa M. , Saluja Sonakshi , Nandan Vagisha , Urpelainen Johannes 
Published: January 2023

AbstractCOVID-19 continues to exact a substantial toll on health. While mortality and morbidity associated with the pandemic are the most obvious impacts, social and economic disruptions are becoming apparent. There is reason to believe that the COVID-19 pandemic has slowed or reversed gains in clean household energy use in rural India. Here we describe phone surveys deployed repeatedly in Jharkhand and Bihar to describe pandemic-related changes in household socio-economic conditions and energy-use patterns. Over three-quarters of households reported hardships during the pandemic, including loss of employment and an inability to search for jobs. In turn, some of these households relied more on polluting fuels. Despite nearly all households preferring gas and electricity, we observed varied behaviours related to the cost of and access to these modern energy sources. We highlight the success of India’s three-free-cylinders scheme, with 90% of households aware of the programme and utilizing at least one free cylinder. These findings illustrate the utility of high-frequency energy-related questionnaires and suggest that interventions to improve clean fuel accessibility and affordability can increase the resilience of transitions to clean household energy.
Chem-map profiles drug binding to chromatin in cells
Authors: Yu Zutao , Spiegel Jochen , Melidis Larry , Hui Winnie W. I. , Zhang Xiaoyun , Radzevičius Antanas , Balasubramanian Shankar 
Published: January 2023

AbstractCharacterizing drug–target engagement is essential to understand how small molecules influence cellular functions. Here we present Chem-map for in situ mapping of small molecules that interact with DNA or chromatin-associated proteins, utilizing small-molecule-directed transposase Tn5 tagmentation. We demonstrate Chem-map for three distinct drug-binding modalities as follows: molecules that target a chromatin protein, a DNA secondary structure or that intercalate in DNA. We map the BET bromodomain protein-binding inhibitor JQ1 and provide interaction maps for DNA G-quadruplex structure-binding molecules PDS and PhenDC3. Moreover, we determine the binding sites of the widely used anticancer drug doxorubicin in human leukemia cells; using the Chem-map of doxorubicin in cells exposed to the histone deacetylase inhibitor tucidinostat reveals the potential clinical advantages of this combination therapy. In situ mapping with Chem-map of small-molecule interactions with DNA and chromatin proteins provides insights that will enhance understanding of genome and chromatin function and therapeutic interventions.
Precise transcript targeting by CRISPR-Csm complexes
Authors: Colognori David , Trinidad Marena , Doudna Jennifer A. 
Published: January 2023

AbstractRobust and precise transcript targeting in mammalian cells remains a difficult challenge using existing approaches due to inefficiency, imprecision and subcellular compartmentalization. Here we show that the clustered regularly interspaced short palindromic repeats (CRISPR)-Csm complex, a multiprotein effector from type III CRISPR immune systems in prokaryotes, provides surgical RNA ablation of both nuclear and cytoplasmic transcripts. As part of the most widely occurring CRISPR adaptive immune pathway, CRISPR-Csm uses a programmable RNA-guided mechanism to find and degrade target RNA molecules without inducing indiscriminate trans-cleavage of cellular RNAs, giving it an important advantage over the CRISPR-Cas13 family of enzymes. Using single-vector delivery of the Streptococcus thermophilus Csm complex, we observe high-efficiency RNA knockdown (90–99%) and minimal off-target effects in human cells, outperforming existing technologies including short hairpin RNA- and Cas13-mediated knockdown. We also find that catalytically inactivated Csm achieves specific and durable RNA binding, a property we harness for live-cell RNA imaging. These results establish the feasibility and efficacy of multiprotein CRISPR-Cas effector complexes as RNA-targeting tools in eukaryotes.
Towards a structurally resolved human protein interaction network
Authors: Burke David F. , Bryant Patrick , Barrio-Hernandez Inigo , Memon Danish , Pozzati Gabriele , Shenoy Aditi , Zhu Wensi , Dunham Alistair S. , Albanese Pascal , Keller Andrew , Scheltema Richard A. , Bruce James E. , Leitner Alexander , Kundrotas Petras , Beltrao Pedro , Elofsson Arne 
Published: January 2023

AbstractCellular functions are governed by molecular machines that assemble through protein-protein interactions. Their atomic details are critical to studying their molecular mechanisms. However, fewer than 5% of hundreds of thousands of human protein interactions have been structurally characterized. Here we test the potential and limitations of recent progress in deep-learning methods using AlphaFold2 to predict structures for 65,484 human protein interactions. We show that experiments can orthogonally confirm higher-confidence models. We identify 3,137 high-confidence models, of which 1,371 have no homology to a known structure. We identify interface residues harboring disease mutations, suggesting potential mechanisms for pathogenic variants. Groups of interface phosphorylation sites show patterns of co-regulation across conditions, suggestive of coordinated tuning of multiple protein interactions as signaling responses. Finally, we provide examples of how the predicted binary complexes can be used to build larger assemblies helping to expand our understanding of human cell biology.
Development and validation of a nomogram model for individualized prediction of hypertension risk in patients with type 2 diabetes mellitus
Authors: Yang Jing , Wang Xuan , Jiang Sheng 
Published: January 2023

AbstractType 2 diabetes mellitus (T2DM) with hypertension (DH) is the most common diabetic comorbidity. Patients with DH have significantly higher rates of cardiovascular disease morbidity and mortality. The objective of this study was to develop and validate a nomogram model for the prediction of an individual's risk of developing DH. A total of 706 T2DM patients who met the criteria were selected and divided into a training set (n = 521) and a validation set (n = 185) according to the discharge time of patients. By using multivariate logistic regression analysis and stepwise regression, the DH nomogram prediction model was created. Calibration curves were used to evaluate the model's accuracy, while decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to evaluate the model's clinical applicability and discriminatory power. Age, body mass index (BMI), diabetic nephropathy (DN), and diabetic retinopathy (DR) were all independent risk factors for DH (P < 0.05). Based on independent risk factors identified by multivariate logistic regression, the nomogram model was created. The model produces accurate predictions. If the total nomogram score is greater than 120, there is a 90% or higher chance of developing DH. In the training and validation sets, the model's ROC curves are 0.762 (95% CI 0.720–0.803) and 0.700 (95% CI 0.623–0.777), respectively. The calibration curve demonstrates that there is good agreement between the model’s predictions and the actual outcomes. The decision curve analysis findings demonstrated that the nomogram model was clinically helpful throughout a broad threshold probability range. The DH risk prediction nomogram model constructed in this study can help clinicians identify individuals at high risk for DH at an early stage, which is a guideline for personalized prevention and treatments.