bluuebunny/crossref_metadata_2025 huggingface dataset:
Low NCOR2 levels in multiple myeloma patients drive multidrug resistance via MYC upregulation
Authors: Mori Tomoaki , Verma Rakesh , Nakamoto-Matsubara Rie , Siu Ka Tat , Panaroni Cristina , Fulzele Keertik S. , Mukaihara Kenta , Onyewadume Chukwuamaka , Maebius Allison , Kato Hiroki , Wong Lai Ping , Sadreyev Ruslan I. , Scadden David T. , Raje Noopur S.
Published: December 2021

MYC upregulation is associated with multidrug refractory disease in patients with multiple myeloma (MM). We, isolated patient-derived MM cells with high MYC expression and discovered that NCOR2 was down-regulated in these cells. NCOR2 is a transcriptional coregulatory protein and its role in MM remains unknown. To define the role of NCOR2 in MM, we created NCOR2 knockout human myeloma cell lines and demonstrated that NCOR2 knockout led to high MYC expression. Furthermore, NCOR2 knockout conferred resistance to pomalidomide, BET and HDAC inhibitors, independent of Cereblon (CRBN), indicating high MYC expression as a cause of multidrug resistance. Moreover, NCOR2 interacted with the nucleosome remodeling and deacetylase (NuRD) complex and repressed the expression of CD180 by directly binding to its promoter and inducing MYC expression. Next, we generated lenalidomide-resistant and pomalidomide-resistant human myeloma cell lines. Whole-exome sequencing revealed that these cell lines acquired the same exonic mutations of NCOR2. These cell lines showed NCOR2 downregulation and MYC upregulation independent of CRBN and demonstrated resistance to BET and HDAC inhibitors. Our findings reveal a novel CRBN independent molecular mechanism associated with drug resistance. Low NCOR2 expression can serve as a potential biomarker for drug resistance and needs further validation in larger prospective studies.
HP1a-mediated heterochromatin formation inhibits high dietary sugar-induced tumor progression
Authors: Chang Che-Wei , Shen Yu-Chia , Yan Shian-Jang
Published: December 2021

High dietary sugar (HDS) is a modern dietary concern that involves excessive consumption of carbohydrates and added sugars, and increases the risk of metabolic disorders and associated cancers. However, epigenetic mechanisms by which HDS induces tumor progression remain unclear. Here, we investigate the role of heterochromatin, an important yet poorly understood part of the epigenome, in HDS-induced tumor progression of Drosophila Ras/Src and Ras/scrib tumor systems. We found that increased heterochromatin formation with overexpression of heterochromatin protein 1a (HP1a), specifically in tumor cells, not only decreases HDS-induced tumor growth/burden but also drastically improves survival of Drosophila with HDS and Ras/Src or Ras/scrib tumors. Moreover, HDS reduces heterochromatin levels in tumor cells. Mechanistically, we demonstrated that increased heterochromatin formation decreases wingless (wg) and Hippo (Hpo) signaling, thereby promoting apoptosis, via inhibition of Yorkie (Yki) nuclear accumulation and upregulation of apoptotic genes, and reduces DNA damage in tumor cells under HDS. Taken together, our work identified a novel epigenetic mechanism by which HP1a-mediated heterochromatin formation suppresses HDS-induced tumor progression likely by decreasing wingless and Hippo signaling, increasing apoptosis, and maintaining genome stability. Our model explains that the molecular, cellular, and organismal aspects of HDS-aggravated tumor progression are dependent on heterochromatin formation, and highlights heterochromatin as a therapeutic target for cancers associated with HDS-induced metabolic disorders.
Matrix stiffness modulates hepatic stellate cell activation into tumor-promoting myofibroblasts via E2F3-dependent signaling and regulates malignant progression
Authors: Liu Zhikui , Mo Huanye , Liu Runkun , Niu Yongshen , Chen Tianxiang , Xu Qiuran , Tu Kangsheng , Yang Nan
Published: December 2021

The hepatic stellate cells (HSCs) activation by myofibroblastic differentiation is critical for liver fibrosis. Crosstalk between stromal cells and tumor cells in the microenvironment alters the properties and facilitates the growth and metastasis of tumor cells. How mechanical stimuli originally stiffness of extracellular matrix (ECM) contribute to tumor development remains poorly understood. Here, we demonstrated that stiffness contributes to mechanosignal transduction in HSCs, which promotes hepatocellular carcinoma (HCC) cells growth and metastasis through secretion of FGF2. On stiffness matrix, HSCs activation was confirmed by immunofluorescence (IF) and Western blot (WB) for α-smooth muscle actin (SMA). Increasing matrix stiffness promoted HSCs activation by CD36-AKT-E2F3 mechanosignaling through shRNA-mediated E2F3 knockdown, AKT inhibitors, and CD36 shRNA. Moreover, ChIP-qPCR. Confirmed that E2F3 combined the promoter of FGF2, and stiffness promoted FGF2 expression. On a stiff matrix, HCC cells cultured with conditioned media (CM) from HSCs increased HCC cells growth and metastasis by binding FGFR1 to activate PI3K/AKT and MEK/ERK signaling pathways. Moreover, conditional E2F3 knockout mice were subjected to CCl4 treatment to assess the role of E2F3 in HSC activation. Additionally, the DEN-induced HCC model was also used to evaluate the role of E2F3 in liver fibrosis and HCC growth. In conclusion, we demonstrated that stiffness-induced HSC activation by E2F3 dependent. Stiffness activated CD36-AKT-E2F3 signaling and targeted FGF2 transcription, subsequently, activated HCC growth and metastasis by FGFR1-mediated PI3K/AKT and MEK/ERK signaling.
Oligodendrocytes depend on MCL-1 to prevent spontaneous apoptosis and white matter degeneration
Authors: Cleveland Abigail H. , Romero-Morales Alejandra , Azcona Laurent Alfonso , Herrero Melisa , Nikolova Viktoriya D. , Moy Sheryl , Elroy-Stein Orna , Gama Vivian , Gershon Timothy R.
Published: December 2021

Neurologic disorders often disproportionately affect specific brain regions, and different apoptotic mechanisms may contribute to white matter pathology in leukodystrophies or gray matter pathology in poliodystrophies. We previously showed that neural progenitors that generate cerebellar gray matter depend on the anti-apoptotic protein BCL-xL. Conditional deletion of Bcl-xL in these progenitors produces spontaneous apoptosis and cerebellar hypoplasia, while similar conditional deletion of Mcl-1 produces no phenotype. Here we show that, in contrast, postnatal oligodendrocytes depend on MCL-1. We found that brain-wide Mcl-1 deletion caused apoptosis specifically in mature oligodendrocytes while sparing astrocytes and oligodendrocyte precursors, resulting in impaired myelination and progressive white matter degeneration. Disabling apoptosis through co-deletion of Bax or Bak rescued white matter degeneration, implicating the intrinsic apoptotic pathway in Mcl-1-dependence. Bax and Bak co-deletions rescued different aspects of the Mcl-1-deleted phenotype, demonstrating their discrete roles in white matter stability. MCL-1 protein abundance was reduced in eif2b5-mutant mouse model of the leukodystrophy vanishing white matter disease (VWMD), suggesting the potential for MCL-1 deficiency to contribute to clinical neurologic disease. Our data show that oligodendrocytes require MCL-1 to suppress apoptosis, implicate MCL-1 deficiency in white matter pathology, and suggest apoptosis inhibition as a leukodystrophy therapy.
2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA
Authors: Pantic Boris , Ives Daniel , Mennuni Mara , Perez-Rodriguez Diego , Fernandez-Pelayo Uxoa , Lopez de Arbina Amaia , Muñoz-Oreja Mikel , Villar-Fernandez Marina , Dang Thanh-mai Julie , Vergani Lodovica , Johnston Iain G. , Pitceathly Robert D. S. , McFarland Robert , Hanna Michael G. , Taylor Robert W. , Holt Ian J. , Spinazzola Antonella
Published: December 2021

Pathological variants of human mitochondrial DNA (mtDNA) typically co-exist with wild-type molecules, but the factors driving the selection of each are not understood. Because mitochondrial fitness does not favour the propagation of functional mtDNAs in disease states, we sought to create conditions where it would be advantageous. Glucose and glutamine consumption are increased in mtDNA dysfunction, and so we targeted the use of both in cells carrying the pathogenic m.3243A>G variant with 2-Deoxy-D-glucose (2DG), or the related 5-thioglucose. Here, we show that both compounds selected wild-type over mutant mtDNA, restoring mtDNA expression and respiration. Mechanistically, 2DG selectively inhibits the replication of mutant mtDNA; and glutamine is the key target metabolite, as its withdrawal, too, suppresses mtDNA synthesis in mutant cells. Additionally, by restricting glucose utilization, 2DG supports functional mtDNAs, as glucose-fuelled respiration is critical for mtDNA replication in control cells, when glucose and glutamine are scarce. Hence, we demonstrate that mitochondrial fitness dictates metabolite preference for mtDNA replication; consequently, interventions that restrict metabolite availability can suppress pathological mtDNAs, by coupling mitochondrial fitness and replication.
Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome
Authors: Gao Aibo , Su Junlei , Liu Ruixin , Zhao Shaoqian , Li Wen , Xu Xiaoqiang , Li Danjie , Shi Juan , Gu Bin , Zhang Juan , Li Qi , Wang Xiaolin , Zhang Yifei , Xu Yu , Lu Jieli , Ning Guang , Hong Jie , Bi Yufang , Gu Weiqiong , Wang Jiqiu , Wang Weiqing
Published: December 2021

Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.
Monitoring the binding and insertion of a single transmembrane protein by an insertase
Authors: Laskowski Pawel R. , Pluhackova Kristyna , Haase Maximilian , Lang Brian M. , Nagler Gisela , Kuhn Andreas , Müller Daniel J.
Published: December 2021

Cells employ highly conserved families of insertases and translocases to insert and fold proteins into membranes. How insertases insert and fold membrane proteins is not fully known. To investigate how the bacterial insertase YidC facilitates this process, we here combine single-molecule force spectroscopy and fluorescence spectroscopy approaches, and molecular dynamics simulations. We observe that within 2 ms, the cytoplasmic α-helical hairpin of YidC binds the polypeptide of the membrane protein Pf3 at high conformational variability and kinetic stability. Within 52 ms, YidC strengthens its binding to the substrate and uses the cytoplasmic α-helical hairpin domain and hydrophilic groove to transfer Pf3 to the membrane-inserted, folded state. In this inserted state, Pf3 exposes low conformational variability such as typical for transmembrane α-helical proteins. The presence of YidC homologues in all domains of life gives our mechanistic insight into insertase-mediated membrane protein binding and insertion general relevance for membrane protein biogenesis.
A genetically encoded fluorescent biosensor for extracellular l-lactate
Authors: Nasu Yusuke , Murphy-Royal Ciaran , Wen Yurong , Haidey Jordan N. , Molina Rosana S. , Aggarwal Abhi , Zhang Shuce , Kamijo Yuki , Paquet Marie-Eve , Podgorski Kaspar , Drobizhev Mikhail , Bains Jaideep S. , Lemieux M. Joanne , Gordon Grant R. , Campbell Robert E.
Published: December 2021

l-Lactate, traditionally considered a metabolic waste product, is increasingly recognized as an important intercellular energy currency in mammals. To enable investigations of the emerging roles of intercellular shuttling of l-lactate, we now report an intensiometric green fluorescent genetically encoded biosensor for extracellular l-lactate. This biosensor, designated eLACCO1.1, enables cellular resolution imaging of extracellular l-lactate in cultured mammalian cells and brain tissue.
Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome
Authors: Roostaei Tina , Klein Hans-Ulrich , Ma Yiyi , Felsky Daniel , Kivisäkk Pia , Connor Sarah M. , Kroshilina Alexandra , Yung Christina , Kaskow Belinda J. , Shao Xiaorong , Rhead Brooke , Ordovás José M. , Absher Devin M. , Arnett Donna K. , Liu Jia , Patsopoulos Nikolaos , Barcellos Lisa F. , Weiner Howard L. , De Jager Philip L.
Published: December 2021

Identifying the effects of genetic variation on the epigenome in disease-relevant cell types can help advance our understanding of the first molecular contributions of genetic susceptibility to disease onset. Here, we establish a genome-wide map of DNA methylation quantitative trait loci in CD4+ T-cells isolated from multiple sclerosis patients. Utilizing this map in a colocalization analysis, we identify 19 loci where the same haplotype drives both multiple sclerosis susceptibility and local DNA methylation. We also identify two distant methylation effects of multiple sclerosis susceptibility loci: a chromosome 16 locus affects PRDM8 methylation (a chromosome 4 region not previously associated with multiple sclerosis), and the aggregate effect of multiple sclerosis-associated variants in the major histocompatibility complex influences DNA methylation near PRKCA (chromosome 17). Overall, we present a new resource for a key cell type in inflammatory disease research and uncover new gene targets for the study of predisposition to multiple sclerosis.
Evaluation of fNIRS signal components elicited by cognitive and hypercapnic stimuli
Authors: Reddy Pratusha , Izzetoglu Meltem , Shewokis Patricia A. , Sangobowale Michael , Diaz-Arrastia Ramon , Izzetoglu Kurtulus
Published: December 2021

Functional near infrared spectroscopy (fNIRS) measurements are confounded by signal components originating from multiple physiological causes, whose activities may vary temporally and spatially (across tissue layers, and regions of the cortex). Furthermore, the stimuli can induce evoked effects, which may lead to over or underestimation of the actual effect of interest. Here, we conducted a temporal, spectral, and spatial analysis of fNIRS signals collected during cognitive and hypercapnic stimuli to characterize effects of functional versus systemic responses. We utilized wavelet analysis to discriminate physiological causes and employed long and short source-detector separation (SDS) channels to differentiate tissue layers. Multi-channel measures were analyzed further to distinguish hemispheric differences. The results highlight cardiac, respiratory, myogenic, and very low frequency (VLF) activities within fNIRS signals. Regardless of stimuli, activity within the VLF band had the largest contribution to the overall signal. The systemic activities dominated the measurements from the short SDS channels during cognitive stimulus, but not hypercapnic stimulus. Importantly, results indicate that characteristics of fNIRS signals vary with type of the stimuli administered as cognitive stimulus elicited variable responses between hemispheres in VLF band and task-evoked temporal effect in VLF, myogenic and respiratory bands, while hypercapnic stimulus induced a global response across both hemispheres.
Comparative study of heat and mass transfer of generalized MHD Oldroyd-B bio-nano fluid in a permeable medium with ramped conditions
Authors: Wang Fuzhang , Rehman Sadique , Bouslimi Jamel , Khaliq Hammad , Qureshi Muhammad Imran , Kamran Muhammad , Alharbi Abdulaziz N. , Ahmad Hijaz , Farooq Aamir
Published: December 2021

This article aims to investigate the heat and mass transfer of MHD Oldroyd-B fluid with ramped conditions. The Oldroyd-B fluid is taken as a base fluid (Blood) with a suspension of gold nano-particles, to make the solution of non-Newtonian bio-magnetic nanofluid. The surface medium is taken porous. The well-known equation of Oldroyd-B nano-fluid of integer order derivative has been generalized to a non-integer order derivative. Three different types of definitions of fractional differential operators, like Caputo, Caputo-Fabrizio, Atangana-Baleanu (will be called later as $$C,CF,AB$$

C
,
C
F
,
A
B

) are used to develop the resulting fractional nano-fluid model. The solution for temperature, concentration, and velocity profiles is obtained via Laplace transform and for inverse two different numerical algorithms like Zakian’s, Stehfest’s are utilized. The solutions are also shown in tabular form. To see the physical meaning of various parameters like thermal Grashof number, Radiation factor, mass Grashof number, Schmidt number, Prandtl number etc. are explained graphically and theoretically. The velocity and temperature of nanofluid decrease with increasing the value of gold nanoparticles, while increase with increasing the value of both thermal Grashof number and mass Grashof number. The Prandtl number shows opposite behavior for both temperature and velocity field. It will decelerate both the profile. Also, a comparative analysis is also presented between ours and the existing findings.
FIN-PRINT a fully-automated multi-stage deep-learning-based framework for the individual recognition of killer whales
Authors: Bergler Christian , Gebhard Alexander , Towers Jared R. , Butyrev Leonid , Sutton Gary J. , Shaw Tasli J. H. , Maier Andreas , Nöth Elmar
Published: December 2021

Biometric identification techniques such as photo-identification require an array of unique natural markings to identify individuals. From 1975 to present, Bigg’s killer whales have been photo-identified along the west coast of North America, resulting in one of the largest and longest-running cetacean photo-identification datasets. However, data maintenance and analysis are extremely time and resource consuming. This study transfers the procedure of killer whale image identification into a fully automated, multi-stage, deep learning framework, entitled FIN-PRINT. It is composed of multiple sequentially ordered sub-components. FIN-PRINT is trained and evaluated on a dataset collected over an 8-year period (2011–2018) in the coastal waters off western North America, including 121,000 human-annotated identification images of Bigg’s killer whales. At first, object detection is performed to identify unique killer whale markings, resulting in 94.4% recall, 94.1% precision, and 93.4% mean-average-precision (mAP). Second, all previously identified natural killer whale markings are extracted. The third step introduces a data enhancement mechanism by filtering between valid and invalid markings from previous processing levels, achieving 92.8% recall, 97.5%, precision, and 95.2% accuracy. The fourth and final step involves multi-class individual recognition. When evaluated on the network test set, it achieved an accuracy of 92.5% with 97.2% top-3 unweighted accuracy (TUA) for the 100 most commonly photo-identified killer whales. Additionally, the method achieved an accuracy of 84.5% and a TUA of 92.9% when applied to the entire 2018 image collection of the 100 most common killer whales. The source code of FIN-PRINT can be adapted to other species and will be publicly available.
Decision aid and cost compensation influence uptake of PSA-based early detection without affecting decisional conflict: a cluster randomised trial
Authors: Tiedje Dorothee , Borowski Matthias , Simbrich Alexandra , Schlößler Kathrin , Kruse Klaus , Bothe Christiane , Kuss Katrin , Adarkwah Charles Christian , Maisel Peter , Jendyk Ralf , Kurosinski Marc-André , Gerß Joachim , Tschuschke Christian , Becker Ralf , Roobol Monique J. , Bangma Chris H. , Hense Hans-Werner , Donner-Banzhoff Norbert , Semjonow Axel
Published: December 2021

International guidelines recommend to inform men about the benefits and harms of prostate specific antigen (PSA) based early detection of prostate cancer. This study investigates the influence of a transactional decision aid (DA) or cost compensation (CC) for a PSA test on the decisional behaviour of men. Prospective, cluster-randomised trial to compare two interventions in a 2 × 2 factorial design: DA versus counselling as usual, and CC versus noCC for PSA-testing. 90 cluster-randomised physicians in the administrative district of Muenster, Germany recruited 962 participants aged 55–69 yrs. in 2018. Primary endpoint: the influence of the DA and CC on the decisional conflict. Secondary endpoints: factors which altered the involvement of the men regarding their decision to take a PSA-test. The primary endpoint was analysed by a multivariate regression model. The choice to take the PSA test was increased by CC and reduced by the DA, the latter also reduced PSA uptake in men who were offered CC. The DA led to an increase of the median knowledge about early detection, changed willingness to perform a PSA test without increasing the level of shared decision, giving participants a stronger feeling of having made the decision by themselves. The DA did not alter the decisional conflict, as it was very low in all study groups. DA reduced and CC increased the PSA uptake. The DA seemed to have a greater impact on the participants than CC, as it led to fewer PSA tests even if CC was granted.

Trial registration: German Clinical Trial Register (Deutsches Register Klinischer Studien DRKS00007687). Registered: 06/05/2015. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007687.
First-principles based simulations of electronic transmission in ReS2/WSe2 and ReS2/MoSe2 type-II vdW heterointerfaces
Authors: Saha Dipankar , Lodha Saurabh
Published: December 2021

Electronic transmission in monolayer ReS$$_{2}$$

2

and ReS$$_{2}$$

2

based van der Waals (vdW) heterointerfaces are studied here. Since ReS$$_{2}$$

2

/WSe$$_{2}$$

2

and ReS$$_{2}$$

2

/MoSe$$_{2}$$

2

type-II vdW heterostructures are suitable for near infrared (NIR)/short-wave infrared (SWIR) photodetection, the role of interlayer coupling at the heterointerfaces is examined in this work. Besides, a detailed theoretical study is presented employing density functional theory (DFT) and nonequilibrium Green’s function (NEGF) combination to analyse the transmission spectra of the two-port devices with ReS$$_{2}$$

2

/WSe$$_{2}$$

2

and ReS$$_{2}$$

2

/MoSe$$_{2}$$

2

channels and compare the near-equilibrium conductance values. Single layer distorted 1T ReS$$_{2}$$

2

exhibits formation of parallel chains of ‘Re’-‘Re’ bonds, leading to in-plane anisotropy. Owing to this structural anisotropy, the charge carrier transport is very much orientation dependent in ReS$$_{2}$$

2

. Therefore, this work is further extended to investigate the role of clusterized ‘Re’  atoms in electronic transmission.
Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis
Authors: Treves Nir , Mor Noa , Allegaert Karel , Bassalov Hely , Berkovitch Matitiahu , Stolar Orit E. , Matok Ilan
Published: December 2021

Despite the increased use of medical cannabinoids, the efficacy and safety of the treatment among children remain uncertain. The objective was to study the efficacy and safety of medical cannabinoids in children. The search included studies through 11-May-2020. Selection criteria included studies evaluating efficacy and safety outcomes of medical cannabinoids (tetrahydrocannabinol, cannabidiol and other cannabis derivatives) versus control in children, independently assessed by two reviewers. Eight studies were included, all of which are randomized controlled trials. Cannabidiol is associated with 50% reduction in seizures rate (Relative Risk (RR) = 1.69, 95% CI [1.20–2.36]) and caregiver global impression of change (Median Estimated difference = (− 1), 95%CI [− 1.39–(− 0.60)]) in Dravet syndrome, compared to placebo. While cannabidiol was associated with a reduction in reported seizure events (RR = 0.59, 95% CI [0.36–0.97]), no association was found in products contained also tetrahydrocannabinol (RR = 1.35, 95% CI [0.46–4.03]). Higher dose of cannabidiol was associated with decreased appetite (RR = 2.40, 95% CI [1.39–4.15]). A qualitative assessment suggests that medical cannabinoids might be associated with adverse mental events. In conclusion, cannabidiol is associated with clinical improvement in Dravet syndrome. However, cannabidiol is also associated with decreased appetite. Adverse mental events were reported as well, however, more research should be performed to assess well this outcome.
Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells
Authors: Sheng Yanghui , Chen Lujing , Ren Xiaozhi , Jiang Zheng , Yau King-Wai
Published: December 2021

Intrinsically-photosensitive retinal ganglion cells (ipRGCs) are non-rod/non-cone retinal photoreceptors expressing the visual pigment, melanopsin, to detect ambient irradiance for various non-image-forming visual functions. The M1-subtype, amongst the best studied, mediates primarily circadian photoentrainment and pupillary light reflex. Their intrinsic light responses are more prolonged than those of rods and cones even at the single-photon level, in accordance with the typically slower time course of non-image-forming vision. The short (OPN4S) and long (OPN4L) alternatively-spliced forms of melanopsin proteins are both present in M1-ipRGCs, but their functional difference is unclear. We have examined this point by genetically removing the Opn4 gene (Opn4−/−) in mouse and re-expressing either OPN4S or OPN4L singly in Opn4−/− mice by using adeno-associated virus, but found no obvious difference in their intrinsic dim-flash responses. Previous studies have indicated that two dominant slow steps in M1-ipRGC phototransduction dictate these cells’ intrinsic dim-flash-response kinetics, with time constants (τ1 and τ2) at room temperature of ~ 2 s and ~ 20 s, respectively. Here we found that melanopsin inactivation by phosphorylation or by β-arrestins may not be one of these two steps, because their genetic disruptions did not prolong the two time constants or affect the response waveform. Disruption of GAP (GTPase-Activating-Protein) activity on the effector enzyme, PLCβ4, in M1-ipRGC phototransduction to slow down G-protein deactivation also did not prolong the response decay, but caused its rising phase to become slightly sigmoidal by giving rise to a third time constant, τ3, of ~ 2 s (room temperature). This last observation suggests that GAP-mediated G-protein deactivation does partake in the flash-response termination, although normally with a time constant too short to be visible in the response waveform.
Association between ambient air pollution and perceived stress in pregnant women
Authors: Lamichhane Dirga Kumar , Jung Dal-Young , Shin Yee-Jin , Lee Kyung-Sook , Lee So-Yeon , Ahn Kangmo , Kim Kyung Won , Shin Youn Ho , Suh Dong In , Hong Soo-Jong , Kim Hwan-Cheol
Published: December 2021

Air pollution may influence prenatal maternal stress, but research evidence is scarce. Using data from a prospective cohort study conducted on pregnant women (n = 2153), we explored the association between air pollution and perceived stress, which was assessed using the 14-item Perceived Stress Scale (PSS), among pregnant women. Average exposures to particulate matter with an aerodynamic diameter of < 2.5 µm (PM2.5) or < 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) for each trimester and the entire pregnancy were estimated at maternal residential addresses using land-use regression models. Linear regression models were applied to estimate associations between PSS scores and exposures to each air pollutant. After adjustment for potential confounders, interquartile-range (IQR) increases in whole pregnancy exposures to PM2.5, PM10, and O3in the third trimester were associated with 0.37 (95% confidence interval [CI] 0.01, 0.74), 0.54 (95% CI 0.11, 0.97), and 0.30 (95% CI 0.07, 0.54) point increases in prenatal PSS scores, respectively. Furthermore, these associations were more evident in women with child-bearing age and a lower level of education. Also, the association between PSS scores and PM10was stronger in the spring. Our findings support the relationship between air pollution and prenatal maternal stress.
Flavivirus infections induce a Golgi stress response in vertebrate and mosquito cells
Authors: Viettri Mercedes , Zambrano José L. , Rosales Romel , Caraballo Gerson I. , Gutiérrez-Escolano Ana Lorena , Ludert Juan E.
Published: December 2021

The stress of the Golgi apparatus is an autoregulatory mechanism that is induced to compensate for greater demand in the Golgi functions. No examples of Golgi stress responses due to physiological stimuli are known. Furthermore, the impact on this organelle of viral infections that occupy the vesicular transport during replication is unknown. In this work, we evaluated if a Golgi stress response is triggered during dengue and Zika viruses replication, two flaviviruses whose replicative cycle is heavily involved with the Golgi complex, in vertebrate and mosquito cells. Using GM-130 as a Golgi marker, and treatment with monensin as a positive control for the induction of the Golgi stress response, a significant expansion of the Golgi cisternae was observed in BHK-21, Vero E6 and mosquito cells infected with either virus. Activation of the TFE3 pathway was observed in the infected cells as indicated by the translocation from the cytoplasm to the nucleus of TFE3 and increased expression of pathway targeted genes. Of note, no sign of activation of the stress response was observed in CRFK cells infected with Feline Calicivirus (FCV), a virus released by cell lysis, not requiring vesicular transport. Finally, dilatation of the Golgi complex and translocation of TFE3 was observed in vertebrate cells expressing dengue and Zika viruses NS1, but not NS3. These results indicated that infections by dengue and Zika viruses induce a Golgi stress response in vertebrate and mosquito cells due to the increased demand on the Golgi complex imposed by virion and NS1 processing and secretion.
Alpha-to-beta- and gamma-band activity reflect predictive coding in affective visual processing
Authors: Strube Andreas , Rose Michael , Fazeli Sepideh , Büchel Christian
Published: December 2021

Processing of negative affective pictures typically leads to desynchronization of alpha-to-beta frequencies (ERD) and synchronization of gamma frequencies (ERS). Given that in predictive coding higher frequencies have been associated with prediction errors, while lower frequencies have been linked to expectations, we tested the hypothesis that alpha-to-beta ERD and gamma ERS induced by aversive pictures are associated with expectations and prediction errors, respectively. We recorded EEG while volunteers were involved in a probabilistically cued affective picture task using three different negative valences to produce expectations and prediction errors. Our data show that alpha-to-beta band activity after stimulus presentation was related to the expected valence of the stimulus as predicted by a cue. The absolute mismatch of the expected and actual valence, which denotes an absolute prediction error was related to increases in alpha, beta and gamma band activity. This demonstrates that top-down predictions and bottom-up prediction errors are represented in typical spectral patterns associated with affective picture processing. This study provides direct experimental evidence that negative affective picture processing can be described by neuronal predictive coding computations.
A cross-sectional study of the health status of Swiss primary care physicians
Authors: Sebo Paul , Favrod-Coune Thierry , Mahler Liv , Moussa Amir , Cohidon Christine , Broers Barbara
Published: December 2021

There is limited data on the general health of primary care physicians (PCPs). We aimed to assess the physical and psychological health of Swiss PCPs. We selected a random sample of 1000 PCPs in Western Switzerland. They were asked about their self-rated health status, all medical conditions experienced in the past five years, and the number of days they were hospitalized and off work in 2019. They were also asked whether they had their own general practitioner (GP) and seen a psychiatrist/psychologist in the past 12 months. A total of 503 PCPs were included in the study (women = 51%, GPs = 67%, pediatricians = 19%, gynecologists = 14%). Ninety-four percent considered themselves in good or very good health. In the past five years, PCPs suffered mostly from depression/anxiety (21%), burnout (21%), dyslipidemia (19%) and hypertension (17%). Male and older PCPs had more often cardiovascular disorders, younger PCPs and GPs had more often psychiatric disorders. They were 9% to have been hospitalized (15% for PCPs over 60) and 20% to have been off work (32% for PCPs under 45). Only 47% had their own GP (37% for GPs). They were 16% (mostly female and younger PCPs) to have consulted a psychiatrist/psychologist. In conclusion, although PCPs considered themselves to be in good health, a substantial proportion suffered from a medical condition, mainly psychiatric (depression or burnout) and/or cardiovascular disorders, or were recently hospitalized or off work. Only half had a GP for themselves. These results may be useful for implementing specific health strategies targeting PCPs.
Machine learning application to predict in-situ stresses from logging data
Authors: Ibrahim Ahmed Farid , Gowida Ahmed , Ali Abdulwahab , Elkatatny Salaheldin
Published: December 2021

Determination of in-situ stresses is essential for subsurface planning and modeling, such as horizontal well planning and hydraulic fracture design. In-situ stresses consist of overburden stress (σv), minimum (σh), and maximum (σH) horizontal stresses. The σhand σHare difficult to determine, whereas the overburden stress can be determined directly from the density logs. The σhand σHcan be estimated either from borehole injection tests or theoretical finite elements methods. However, these methods are complex, expensive, or need unavailable tectonic stress data. This study aims to apply different machine learning (ML) techniques, specifically, random forest (RF), functional network (FN), and adaptive neuro-fuzzy inference system (ANFIS), to predict the σhand σHusing well-log data. The logging data includes gamma-ray (GR) log, formation bulk density (RHOB) log, compressional (DTC), and shear (DTS) wave transit-time log. A dataset of 2307 points from two wells (Well-1 and Well-2) was used to build the different ML models. The Well-1 data was used in training and testing the models, and the Well-2 data was used to validate the developed models. The obtained results show the capability of the three ML models to predict accurately the σh and σH using the well-log data. Comparing the results of RF, ANFIS, and FN models for minimum horizontal stress prediction showed that ANFIS outperforms the other two models with a correlation coefficient (R) for the validation dataset of 0.96 compared to 0.91 and 0.88 for RF, and FN, respectively. The three models showed similar results for predicting maximum horizontal stress with R values higher than 0.98 and an average absolute percentage error (AAPE) less than 0.3%. a20index for the actual versus the predicted data showed that the three ML techniques were able to predict the horizontal stresses with a deviation less than 20% from the actual data. For the validation dataset, the RF, ANFIS, and FN models were able to capture all changes in the σhand σHtrends with depth and accurately predict the σhand σHvalues. The outcomes of this study confirm the robust capability of ML to predict σhand σHfrom readily available logging data with no need for additional costs or site investigation.
Post-traumatic peripheral vestibular disorders (excluding positional vertigo) in workers following head injury
Authors: Misale Priyanka , Hassannia Fatemeh , Dabiri Sasan , Brandstaetter Tom , Rutka John
Published: December 2021

Benign paroxysmal positional vertigo has typically been reported to be the most common cause of post-traumatic dizziness. There is however paucity in the literature about other peripheral vestibular disorders post-head injury. This article provides an overview of other causes of non-positional dizziness post-head trauma from our large institutional experience. The UHN WSIB Neurotology database (n = 4291) between 1998 and 2018 was retrospectively studied for those head-injured workers presenting with non-positional peripheral vestibular disorders. All subjects had a detailed neurotological history and examination and vestibular testing including video nystagmography, video head impulse testing (or a magnetic scleral search coil study), vestibular-evoked myogenic potentials, and audiometry. Imaging studies included routine brain and high-resolution temporal bone CT scans and/or brain MRI. Based on a database of 4291 head-injured workers with dizziness, 244 were diagnosed with non-positional peripheral vertigo. Recurrent vestibulopathy (RV) was the most common cause of non-positional post-traumatic vertigo. The incidence of Meniere’s disease in the post-traumatic setting did not appear greater than found in the general population. The clinical spectrum pertaining to recurrent vestibulopathy, Meniere’s disease, delayed endolymphatic hydrops, drop attacks, superior semicircular canal dehiscence syndrome, and uncompensated peripheral vestibular loss are discussed.
Establishment of a miRNA profile in paediatric HIV-1 patients and its potential as a biomarker for effectiveness of the combined antiretroviral therapy
Authors: Consuegra Irene , Gasco Samanta , Serramía María Jesús , Jiménez José Luis , Mellado Maria Jose , Muñoz-Fernández María Ángeles
Published: December 2021

miRNAs have been extensively studied in pathological conditions, including viral infections, such as those provoked by HIV-1. Several cellular and circulating miRNAs are altered during HIV-1 infection, with either beneficial effects on host defenses or enhanced virus infectivity. Blood samples were collected in sterile EDTA tubes and plasma was separated and stored, as were PBMCs. RNA was isolated and reverse-transcribed. Finally, the miRNA gene expression profile was assessed using TaqMan Array Human microRNA Card A v2.0. A comprehensive statistical analysis was performed on the results obtained. This is the first study on miRNAs in HIV-1 paediatric patients, and a miRNA profile differentiating patients starting combination antiretroviral therapy (cART) at different times after HIV-1 diagnosis was established. Thirty-four miRNAs were observed to have different expression levels between the control group and the cART group. The data indicates the need to start cART as soon as possible after the establishment of HIV-1 infection to assure the best outcome possible. Finally, the selected 34 miRNAs may be used as biomarkers for prognosis and assessing therapy effectiveness. However, more research must be conducted to establish adequate quantitative correlations.
Community RNA-Seq: multi-kingdom responses to living versus decaying roots in soil
Authors: Nuccio Erin E , Nguyen Nhu H , Nunes da Rocha Ulisses , Mayali Xavier , Bougoure Jeremy , Weber Peter K , Brodie Eoin , Firestone Mary , Pett-Ridge Jennifer
Published: December 2021

Roots are a primary source of organic carbon input in most soils. The consumption of living and detrital root inputs involves multi-trophic processes and multiple kingdoms of microbial life, but typical microbial ecology studies focus on only one or two major lineages. We used Illumina shotgun RNA sequencing to conduct PCR-independent SSU rRNA community analysis (“community RNA-Seq”) and simultaneously assess the bacteria, archaea, fungi, and microfauna surrounding both living and decomposing roots of the annual grass, Avena fatua. Plants were grown in 13CO2-labeled microcosms amended with 15N-root litter to identify the preferences of rhizosphere organisms for root exudates (13C) versus decaying root biomass (15N) using NanoSIMS microarray imaging (Chip-SIP). When litter was available, rhizosphere and bulk soil had significantly more Amoebozoa, which are potentially important yet often overlooked top-down drivers of detritusphere community dynamics and nutrient cycling. Bulk soil containing litter was depleted in Actinobacteria but had significantly more Bacteroidetes and Proteobacteria. While Actinobacteria were abundant in the rhizosphere, Chip-SIP showed Actinobacteria preferentially incorporated litter relative to root exudates, indicating this group’s more prominent role in detritus elemental cycling in the rhizosphere. Our results emphasize that decomposition is a multi-trophic process involving complex interactions, and our methodology can be used to track the trajectory of carbon through multi-kingdom soil food webs.
Reconstruction of spinel Co3O4 by inert Zn2+ towards enhanced oxygen catalytic activity
Authors: Wang Yifan , Wang Ze-Pan , Wu Huixiang , Hou Liping , Liu Zhao-Qing
Published: December 2021

Oxygen catalytic reaction was promoted by the enhanced utilization rate of highly active Co3+ after the reconstruction of Co3O4.
Photochemical transformation of chlorobenzenes and white phosphorus into arylphosphines and phosphonium salts
Authors: Till Marion , Streitferdt Verena , Scott Daniel J. , Mende Michael , Gschwind Ruth M. , Wolf Robert
Published: December 2021

A simple photochemical procedure is reported for the arylation of white phosphorus with aryl chlorides, using the strong photoreductant tetrakis(dimethylamino)ethylene (TDAE) and UV light irradiation.
A Li+-integrated metallohydrogel-based mixed conductive electrochemical semiconductor
Authors: Kumar Yeeshu , Dubey Mrigendra
Published: December 2021

A metallohydrogel-based ionic–electronic transport-driven electrochemical semiconductor has been developed for soft electronic device applications.
The impact of temperature and unwanted impurities on slow compression of ice
Authors: Tonauer Christina M. , Bauer Marion , Loerting Thomas
Published: December 2021

Slow compression of ice at 100 K usually results in pressure-amorphisation, unless there are ice IX seeds and temperature gradients.
The L–G phase transition in binary Cu–Zr metallic liquids
Authors: An Qi , Johnson William L. , Samwer Konrad , Corona Sydney L. , Shen Yidi , Goddard William A.
Published: December 2021

An identified first-order glass transition from a liquid-like disordered phase (L-phase) to a heterogeneous, elastically rigid, solid-like phase (G-phase).
A chemical dynamics study of the reaction of the methylidyne radical (CH, X2Π) with dimethylacetylene (CH3CCCH3, X1A1g)
Authors: He Chao , Fujioka Kazuumi , Nikolayev Anatoliy A. , Zhao Long , Doddipatla Srinivas , Azyazov Valeriy N. , Mebel Alexander M. , Sun Rui , Kaiser Ralf I.
Published: December 2021

Center-of-mass flux contour map for the reaction of the methylidyne (CH; X2Π) radical with dimethylacetylene (CH3CCCH3; X1A1g) leading to the formation of 1-methyl-3-methylenecyclopropene (13%) and 1-penten-3-yne (81%).
A machine learning approach for predicting the nucleophilicity of organic molecules
Authors: Saini Vaneet , Sharma Aditya , Nivatia Dhruv
Published: December 2021

A neural network model was found to efficiently predict the experimental nucleophilicity values using the quantum mechanical descriptors extracted from organic molecules.
Newly synthesized palladium(ii) complexes with aminothiazole derivatives: in vitro study of antimicrobial activity and antitumor activity on the human prostate cancer cell line
Authors: Simić Dejan , Zarić Milan , Nikolić Ivana , Živković-Zarić Radica , Čanović Petar , Kočović Aleksandar , Radojević Ivana , Raković Ivana , Jovičić Milić Sandra , Petrović Đorđe , Stojković Danijela , Vuković Nenad , Kačániová Miroslava , Vukić Milena , Jevtić Verica
Published: December 2021

Five new complexes of the palladium(ii) ion (C1–C5) having the general formula [(PdL2)]Cl2 with some 2-aminothiazoles have been synthesized and characterized by elemental microanalysis and infrared, 1H NMR and 13C NMR spectroscopy.
Pulsed heating atomic layer deposition (PH-ALD) for epitaxial growth of zinc oxide thin films on c-plane sapphire
Authors: Piercy Brandon D. , Wooding Jamie P. , Gregory Shawn A. , Losego Mark D.
Published: December 2021

High-temperature heat pulses interleaved with ALD cycling enables the growth of heteroepitaxial ZnO on c-plane sapphire substrates. This “pulsed-heating” ALD separates the chemistry delivery process from the material’s structural crystallization.
Investigation on the catalytic behavior of a novel thulium-organic framework with a planar tetranuclear {Tm4} cluster as the active center for chemical CO2 fixation
Authors: Chen Hongtai , Zhang Zhengguo , Lv Hongxiao , Liu Shurong , Zhang Xiutang
Published: December 2021

The exquisite combination of coplanar {Tm4} clusters and structure-oriented functional BDCP5− leads to a highly robust nanoporous Tm-MOF (NUC-37) with high catalytic performance on the chemical fixation of CO2.
Extraordinary role of Zn in enhancing thermoelectric performance of Ga-doped n-type PbTe
Authors: Luo Zhong-Zhen , Cai Songting , Hao Shiqiang , Bailey Trevor P. , Luo Yubo , Luo Wenjun , Yu Yan , Uher Ctirad , Wolverton Christopher , Dravid Vinayak P. , Zou Zhigang , Yan Qingyu , Kanatzidis Mercouri G.
Published: December 2021

The discordant Zn and Ga atoms raise the carrier concentration and soften phonon modes, resulting in superior performance nanostructured n-type PbTe.
A bio-inspired heterodinuclear hydrogenase CoFe complex
Authors: Sun Lili , Adam Suzanne M. , Mokdad Walaa , David Rolf , Milet Anne , Artero Vincent , Duboc Carole
Published: December 2021

The performance for H2 production of a bio-inspired CoFe complex was evaluated and compared to its two efficient FeFe and NiFe analogs. Unexpectedly, it did not show any electrocatalytic activity for H2 production.
Mogroside-rich extract fromSiraitia grosvenoriifruits protects against the depletion of ovarian reserves in aging mice by ameliorating inflammatory stress
Authors: Du Ya , Liu Jiahao , Liu Shaoyuan , Hu Jiahao , Wang Siyuan , Cui Kexin , Yan Ke , Liu Xinxin , Wu Nian-Rong , Yang Xiaogan , Liang Xingwei
Published: December 2021

Mogroside-rich extract (MGE) from Siraitia grosvenorii fruits has beneficial effects on female reproduction of aging mice, including improvement of the estrous cycle and ovarian reserves.
K2S2O8-induced site-selective phenoxazination/phenothiazination of electron-rich anilines
Authors: Zhang He , Wang Shengchun , Wang Xiaoyu , Wang Pengjie , Yi Hong , Zhang Heng , Lei Aiwen
Published: December 2021

By just using cheap K2S2O8 as the oxidant at room temperature in the air, the phenoxazination/phenothiazination of electron-rich anilines to construct or modify triarylamine derivatives has been established.
A multiferroic vanadium phosphide monolayer with ferromagnetic half-metallicity and topological Dirac states
Authors: Xuan Xiaoyu , Wu Menghao , Zhang Zhuhua , Guo Wanlin
Published: December 2021

A highly stable vanadium phosphide monolayer material is predicted to host strongly coupled ferroelasticity and ferromagnetism as well as coexisting half-metallicity and topological Dirac fermions.
Synthesis and optical properties of conjugated maleimide molecules containing amino with aggregation-induced emission enhancement (AIEE)
Authors: Yang Xiaodong , Yamabuki Kazuhiro , Onimura Kenjiro
Published: December 2021

Maleimide-based luminophores bearing conjugated units and various amino substituents are attracting intensive scientific interest as organic luminophores, owing to their excellent light emission properties and wide applications.