bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance spectroscopy of isocitrate dehydrogenase mutated gliomas: current knowledge on the neurochemical profile
Authors: Branzoli Francesca , Marjańska Małgorzata 
Published: June 2020

Purpose of review
Magnetic resonance spectroscopy (MRS) may play a key role for the management of patients with glioma. We highlighted the utility of MRS in the noninvasive diagnosis of gliomas with mutations in isocitrate dehydrogenase (IDH) genes, by providing an overview of the neurochemical alterations observed in different glioma subtypes, as well as during treatment and progression, both in vivo and ex vivo.

Recent findings
D-2-hydroxyglutarate (2HG) decrease during anticancer treatments was recently shown to be associated with altered levels of other metabolites, including lactate, glutamate and glutathione, suggesting that tumour treatment leads to a metabolic reprogramming beyond 2HG depletion. In combination with 2HG quantification, cystathionine and glycine seem to be the most promising candidates for higher specific identification of glioma subtypes and follow-up of disease progression and response to treatment.

Summary
The implementation of advanced MRS methods in the routine clinical practice will allow the quantification of metabolites that are not detectable with conventional methods and may enable immediate, accurate diagnosis of gliomas, which is crucial for planning optimal therapeutic strategies and follow-up examinations. The role of different metabolites as predictors of patient outcome still needs to be elucidated.
Contribution of PET-MRI in brain diseases in clinical practice
Authors: Pyatigorskaya Nadya , Habert Marie-Odile , Rozenblum Laura 
Published: June 2020

Purpose of reviewHybrid PET- MRI is a technique that has the ability to improve diagnostic accuracy in many applications, whereas PET and MRI performed separately often fail to provide accurate responses to clinical questions. Here, we review recent studies and current developments in PET-MRI, focusing on clinical applications.Recent findingsThe combination of PET and MRI imaging methods aims at increasing the potential of each individual modality. Combined methods of image reconstruction and correction of PET-MRI attenuation are being developed, and a number of applications are being introduced into clinical practice. To date, the value of PET-MRI has been demonstrated for the evaluation of brain tumours in epilepsy and neurodegenerative diseases. Continued advances in data analysis regularly improve the efficiency and the potential application of multimodal biomarkers.SummaryPET-MRI provides simultaneous of anatomical, functional, biochemical and metabolic information for the personalized characterization and monitoring of neurological diseases. In this review, we show the advantage of the complementarity of different biomarkers obtained using PET-MRI data. We also present the recent advances made in this hybrid imaging modality and its advantages in clinical practice compared with MRI and PET separately.
Digital technology for management of severe mental disorders in low-income and middle-income countries
Authors: Merchant Rutvij , Torous John , Rodriguez-Villa Elena , Naslund John A. 
Published: June 2020

Purpose of review
Increasingly, digital technologies, especially mobile telecommunications and smartphone apps, are seen as a novel tool for managing severe mental disorders (SMDs) in low-income and middle-income countries (LMICs). However, there is a need to identify best practices in the use of digital technologies to effectively reach, support, and manage care for patients living with SMDs. In this review, we summarize recent studies using digital technology to manage symptoms and support clinical care for this patient population and discuss new opportunities to advance digital psychiatry research and practice in LMICs.

Recent findings
Studies evaluating digital interventions for clinical populations living with SMDs in LMICs are limited. Yet, across recent articles surveyed, digital technology appears to yield diverse benefits for this at-risk patient population. These benefits include improved medication adherence, appointment adherence, reduced instances of relapse, and fewer re-hospitalizations.

Summary
Continued rigorous research evaluating effectiveness and cost-effectiveness of digital technologies in reaching, treating, and managing symptoms and supporting clinical care for patients with SMDs in LMICs is vital. The urgency for remote approaches for delivering specialized psychiatric care is particularly pronounced because of the immediate and long-term impact of the coronavirus (COVID-19) pandemic on access to in-person services. Future research should emphasize participatory approaches rooted in a process of codesign with target users, in order to achieve clinically effective remotely delivered digital mental health interventions.
The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis
Authors: Nampoothiri Sreekala , Sauve Florent , Ternier Gaëtan , Fernandois Daniela , Coelho Caio , Imbernon Monica , Deligia Eleonora , Perbet Romain , Florent Vincent , Baroncini Marc , Pasquier Florence , Trottein François , Maurage Claude-Alain , Mattot Virginie , Giacobini Paolo , Rasika S. , Prevot Vincent 
Published: June 2020

AbstractMost patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extra-pulmonary origin. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to olfactory/gustative and brainstem cardiorespiratory centers. Here, human brain gene-expression analyses and immunohistochemistry reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with genes or pathways involved in physiological functions or viral pathogenesis. A post-mortem patient brain shows viral invasion and replication in both the olfactory bulb and the hypothalamus, while animal studies indicate that sex hormones and metabolic diseases influence this susceptibility.
Characterization of the exopolysaccharide biosynthesis pathway inMyxococcus xanthus
Authors: Pérez-Burgos María , García-Romero Inmaculada , Jung Jana , Schander Eugenia , Valvano Miguel A. , Søgaard-Andersen Lotte 
Published: June 2020

AbstractMyxococcus xanthusarranges into two morphologically distinct biofilms depending on its nutritional status, i.e. coordinately spreading colonies in the presence of nutrients and spore-filled fruiting bodies in the absence of nutrients. A secreted polysaccharide referred to as exopolysaccharide (EPS) is a structural component of both biofilms and is also important for type IV pili-dependent motility and fruiting body formation. Here, we characterize the biosynthetic machinery responsible for EPS biosynthesis using bioinformatics, genetics, heterologous expression, and biochemical experiments. We show that this machinery constitutes a Wzx/Wzy-dependent pathway dedicated to EPS biosynthesis. Our data support that EpsZ (MXAN_7415) is the polyisoprenyl-phosphate hexose-1-phosphate transferase responsible for initiation of the repeat unit synthesis. Heterologous expression experiments support that EpsZ has galactose-1-P transferase activity. Moreover, MXAN_7416, renamed WzxEPS, and MXAN_7442, renamed WzyEPS, are the Wzx flippase and Wzy polymerase responsible for translocation and polymerization of the EPS repeat unit, respectively. Also, in this pathway, EpsV (MXAN_7421) is the polysaccharide co-polymerase and EpsY (MXAN_7417) the outer membrane polysaccharide export (OPX) protein. Mutants with single in-frame deletions in the five corresponding genes had defects in type IV pili-dependent motility and a conditional defect in fruiting body formation. Furthermore, all five mutants were deficient in type IV pili formation and genetic analyses suggest that EPS and/or the EPS biosynthetic machinery stimulates type IV pili extension. Additionally, we identify a polysaccharide biosynthesis gene cluster, which together with an orphan gene encoding an OPX protein make up a complete Wzx/Wzy-dependent pathway for synthesis of an unknown polysaccharide.ImportanceThe secreted polysaccharide referred to as exopolysaccharide (EPS) has important functions in the social life cycle ofM. xanthus; however, little is known about how EPS is synthesized. Here, we characterized the EPS biosynthetic machinery and show that it makes up a Wzx/Wzy-dependent pathway for polysaccharide biosynthesis. Mutants lacking a component of this pathway had reduced type IV pili-dependent motility and a conditional defect in development. Also, these analysis suggest that EPS and/or the EPS biosynthetic machinery is important for type IV pili formation.
Combining Mechanistic Models and Machine Learning for Personalized Chemotherapy and Surgery Sequencing in Breast Cancer
Authors: Axenie Cristian , Kurz Daria 
Published: June 2020

AbstractMathematical and computational oncology has increased the pace of cancer research towards the advancement of personalized therapy. Serving the pressing need to exploit the large amounts of currently underutilized data, such approaches bring a significant clinical advantage in tailoring the therapy. CHIMERA is a novel system that combines mechanistic modelling and machine learning for personalized chemotherapy and surgery sequencing in breast cancer. It optimizes decision-making in personalized breast cancer therapy by connecting tumor growth behaviour and chemotherapy effects through predictive modelling and learning. We demonstrate the capabilities of CHIMERA in learning simultaneously the tumor growth patterns, across several types of breast cancer, and the pharmacokinetics of a typical breast cancer chemotoxic drug. The learnt functions are subsequently used to predict how to sequence the intervention. We demonstrate the versatility of CHIMERA in learning from tumor growth and pharmacokinetics data to provide robust predictions under two, typically used, chemotherapy protocol hypotheses.
Structural basis of a public antibody response to SARS-CoV-2
Authors: Yuan Meng , Liu Hejun , Wu Nicholas C. , Lee Chang-Chun D. , Zhu Xueyong , Zhao Fangzhu , Huang Deli , Yu Wenli , Hua Yuanzi , Tien Henry , Rogers Thomas F. , Landais Elise , Sok Devin , Jardine Joseph G. , Burton Dennis R. , Wilson Ian A. 
Published: June 2020

ABSTRACTMolecular-level understanding of human neutralizing antibody responses to SARS-CoV-2 could accelerate vaccine design and facilitate drug discovery. We analyzed 294 SARS-CoV-2 antibodies and found that IGHV3-53 is the most frequently used IGHV gene for targeting the receptor binding domain (RBD) of the spike (S) protein. We determined crystal structures of two IGHV3-53 neutralizing antibodies +/- Fab CR3022 ranging from 2.33 to 3.11 Å resolution. The germline-encoded residues of IGHV3-53 dominate binding to the ACE2 binding site epitope with no overlap with the CR3022 epitope. Moreover, IGHV3-53 is used in combination with a very short CDR H3 and different light chains. Overall, IGHV3-53 represents a versatile public VH in neutralizing SARS-CoV-2 antibodies, where their specific germline features and minimal affinity maturation provide important insights for vaccine design and assessing outcomes.
The epidemiological signature of pathogen populations that vary in the relationship between free-living survival and virulence
Authors: Gomez Lourdes M. , Meszaros Victor A , Turner Wendy C. , Ogbunugafor C. Brandon 
Published: June 2020

ABSTRACTThe relationship between parasite virulence and transmission is a pillar of evolutionary theory that has specific implications for public health. Part of this canon involves the idea that virulence and free-living survival (a key component of transmission) may have different relationships in different host-parasite systems. Most examinations of the evolution of virulence-transmission relationships—theoretical or empirical in nature—tend to focus on the evolution of virulence, with transmission a secondary consideration. And even within transmission studies, the focus on free-living survival is a smaller subset, though recent studies have examined its importance in the ecology of infectious diseases. Few studies have examined the epidemic-scale consequences of variation in survival across different virulence-survival relationships. In this study, we utilize a mathematical model motivated by aspects of SARS-CoV-2 natural history to investigate how evolutionary changes in survival may influence several aspects of disease dynamics at the epidemiological scale. Across virulence-survival relationships (where these traits are positively or negatively correlated), we found that small changes (5% above and below the nominal value) in survival can have a meaningful effect on certain outbreak features, including theR0, and the size of the infectious peak in the population. These results highlight the importance of properly understanding the mechanistic relationship between virulence and parasite survival, as evolution of increased survival across different relationships with virulence will have considerably different epidemiological signatures.
Quantitative data independent acquisition glycoproteomics of sparkling wine
Authors: Pegg Cassandra L. , Phung Toan K. , Caboche Christopher H. , Niamsuphap Suchada , Bern Marshall , Howell Kate , Schulz Benjamin L. 
Published: June 2020

ABSTRACTSparkling wine is an alcoholic beverage enjoyed around the world. The sensory properties of sparkling wine depend on a complex interplay between the chemical and biochemical components in the final product. Glycoproteins have been linked to positive and negative qualities in sparkling wine, but the glycosylation profiles of sparkling wine have not been previously investigated in detail. We analysed the glyco/proteome of sparkling wines using protein- and glycopeptide-centric approaches. We developed an automated workflow that created ion libraries to analyse Sequential Window Acquisition of all THeoretical mass spectra (SWATH) Data Independent Acquisition (DIA) mass spectrometry data based on glycopeptides identified by Byonic. We applied our workflow to three pairs of experimental sparkling wines to assess the effects of aging on lees and of different yeast strains used in the Liqueur de Tirage for secondary fermentation. We found that aging a cuvée on lees for 24 months compared to 8 months led to a dramatic decrease in overall protein abundance and an enrichment in large glycans at specific sites in some proteins. Secondary fermentation of a Riesling wine withSaccharomyces cerevisiaeyeast strain Siha4 produced more yeast proteins and glycoproteins than withS. cerevisiaeyeast strain DV10. The abundance and glycosylation profiles of grape glycoproteins were also different between grape varieties. This work represents the first in-depth study into protein- and peptide-specific glycosylation in sparkling wines and describes a quantitative glycoproteomic SWATH/DIA workflow that is broadly applicable to other sample types.
Epigenetic Consequences of Hormonal Interactions between Opposite-sex Twin Fetuses
Authors: Kong Siming , Peng Yong , Chen Wei , Ma Xinyi , Wei Yuan , Zhao Yangyu , Li Rong , Yan Liying , Qiao Jie 
Published: June 2020

AbstractIn human opposite-sex twins, certain phenotypic traits of the female are affected negatively by testosterone transfer from the male, while the male may or may not be affected by the femalein utero. However, no study was carried out to uncover the epigenetic basis of these effects. Here, we generated DNA methylation data from 54 newborn twins and histone modification data from 14 newborn twins, including female-female (FF), female-male (FM), and male-male (MM) newborn twins, to exclude the effects of postnatal environment and socialization, and investigated the epigenetic consequences of prenatal interactions between female and male gonadal hormones. We found that FM-Fs (female in FM twins) were distinguishable from FF twins by their DNA methylome, as were FM-Ms (male in FM twins) from MM twins. The correlation between genome-wide DNA methylation of females and males showed that FM-Fs, but not FFs, were closer to males from FM-Ms and MMs. Interestingly, the DNA methylomic differences between FM-Fs and FFs, but not those between FM-Ms and MMs, were linked to cognition and the nervous system. Meanwhile, FM-Ms and MMs, but not FM-Fs and FFs, displayed differential histone modification of H3K4me3, which were linked to immune responses. These findings provide epigenetic evidence for the twin testosterone transfer hypothesis and explain how prenatal hormone exposure is linked to reported and novel traits of childhood and adult through the epigenome in opposite-sex twins.Author SummaryPrenatal exposure to testosterone may affect physiological, cognitive, and behavioral traits in females with male co-twins, while the males in opposite-sex twins present weak and inconsistent influences. In this study, we systematically investigated the hormonal interactions between opposite-sex twins in newborns from epigenetics including DNA methylation and histone modifications. We show that DNA methylome in FM-Fs (female in FM twins) was different from FF twins and their DNA methylomic differences were associated with cognition and the nervous system. We also suggest that FM-Ms (male in FM twins) were distinguishable from MM twins by their DNA methylome and FM-MsversusMMs displayed differential histone modification of H3K4me3, which were linked to immune responses. Our study provides insight into the epigenetic explanation for hormonal influences between opposite-sex fetuses.
Hippocampal hyperactivity in a rat model of Alzheimer’s disease
Authors: Sosulina Liudmila , Mittag Manuel , Geis Hans-Rüdiger , Hoffmann Kerstin , Klyubin Igor , Qi Yingjie , Steffen Julia , Friedrichs Detlef , Henneberg Niklas , Fuhrmann Falko , Justus Daniel , Keppler Kevin , Cuello A. Claudio , Rowan Michael J. , Fuhrmann Martin , Remy Stefan 
Published: June 2020

AbstractNeuronal network dysfunction is a hallmark of Alzheimer’s disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed the hippocampal micronetwork in a rat model of AD at an early disease stage at the beginning of extracellular amyloid beta (Aβ) deposition. We established two-photon Ca2+-imagingin vivoin the hippocampus of rats and found hyperactivity of CA1 neurons. Patch-clamp recordings in brain slicesin vitrorevealed changes in the passive properties and intrinsic excitability of CA1 pyramidal neurons. Furthermore, we observed increased neuronal input resistance and prolonged action potential width in CA1 pyramidal neurons. Surprisingly, all parameters measured to quantify synaptic inhibition and excitation onto CA1 pyramidal neurons were intact suggesting a cell immanent deficit. Our data support the view that altered intrinsic excitability of CA1 neurons may precede inhibitory dysfunction at an early stage of disease progression.
Modulation of Early Mitotic Inhibitor 1 (EMI1) Depletion on the Sensitivity of PARP Inhibitors in BRCA1 Mutated Triple-Negative Breast Cancer Cells
Authors: Moustafa Dina , Abd Elwahed Maha R. , Elsaid Hanaa H. , Parvin Jeffrey D. 
Published: June 2020

AbstractTriple negative breast cancer (TNBC) represents approximately 10–15% of all breast cancers and has a poor outcome as it lacks a receptor target for therapy, and TNBC is frequently associated with a germline mutation ofBRCA1. Poly (ADP-ribose) polymerase inhibitor (PARPi) drugs have demonstrated some effectiveness in treatingBRCA1orBRCA2mutated breast and ovarian cancers but resistance to PARPi is common. Published results found that resistance to Olaparib, a PARPi, can be due to downregulation of EMI1 and the consequent upregulation of the RAD51 recombinase. Using a tissue culture-based cell viability assay, we extended those observations to another PARPi and to other chemotherapy drugs that affect DNA repair or the cell cycle. As we expected, EMI1 downregulation resulted in resistance to another PARPi drug, Talazoparib. EMI1 downregulation also led to resistance to other cytotoxic drugs, Cisplatin and CHK1 inhibitor. Surprisingly, EMI1 depletion also led to resistance to a MEK inhibitor, though this inhibitor blocks cells in G1 phase of the cell cycle and would not be expected to be sensitive to EMI1 levels. Notably, increasing the RAD51 protein expression only partially recapitulated the effects of EMI1 depletion in causing resistance to different PARPi and the other cytotoxic drugs. These results suggest that the downstream effects of EMI1 downregulation that contribute to PARPi resistance are increasing the concentration of RAD51 protein in the cell and blocking mitotic entry. We found that combining CHK1 inhibitor with olaparib results in restoration of sensitivity even when EMI1 expression is downregulated. This combination therapy may be a means to overcome the PARPi resistance in BRCA1-deficient TNBC cells.
(3S,6E)-Nerolidol-mediated rendezvous of Cyclocephalini beetles,Cyclocephala paraguayensis, in bottle gourd flowers
Authors: Favaris Arodí P. , Túler Amanda C. , Silva Weliton D. , Rodrigues Sérgio R. , Leal Walter S. , Bento José M. S. 
Published: June 2020

AbstractCyclocephalini beetles of genusCyclocephala(Coleoptera: Melolonthidae: Dynastinae) use flowers of some plants as food, shelter, and mating stands. However, little is known about floral scent chemistry involved in this interaction. Here we show that a sesquiterpene alcohol mediates attraction ofCyclocephala paraguayensisArrow on bottle gourd flowers,Lagenaria siceraria(Curcubitaceae). Both males and females started to aggregate on flowers at twilight; after that, mating began and remained for the entire night. The major constituent of the airborne volatiles fromL. sicerariawas fully characterized as(3S,6E)-nerolidol, which elicited electroantennographic responses on male and female antennae. Field bioassays showed that traps baited with the natural stereoisomer or a mix of nerolidol isomers captured significantly more males and females ofC. paraguayensisthan control traps. Analysis from the gut content of these Cyclocephalini beetles showed the presence of pollen, suggesting that they also use bottle gourd flowers for their nourishment. Taken together, these results suggest that(3S,6E)-nerolidol plays an essential role in the reproductive behavior ofC. paraguayensisby eliciting aggregation, mating, and feeding.
Organization of cortico-hippocampal networks in the human brain
Authors: Barnett Alexander J. , Reilly Walter , Dimsdale-Zucker Halle R. , Mizrak Eda , Reagh Zachariah , Ranganath Charan 
Published: June 2020

AbstractEpisodic memory depends on interactions between the hippocampus and the interconnected regions comprising default mode network (DMN). Here, using data-driven analyses of resting-state fMRI data, we identified the networks that interact with the hippocampus—the DMN and a “Medial Temporal Network” (MTN) that included regions in the medial temporal lobe and retrosplenial cortex. We observed that the MTN plays a critical role in connecting the visual network to the DMN and hippocampus. The DMN could be further divided into three subnetworks: a “Posterior-Medial” Subnetwork comprised of posterior cingulate, and lateral parietal cortices, an “Anterior-Temporal” Subnetwork comprised of regions in the temporopolar, and dorsomedial prefrontal cortex, and a “Medial-Prefrontal” Subnetwork comprised of regions primarily in the medial prefrontal cortex. These networks vary in their functional connectivity along the hippocampal long-axis and represent different kinds of information during memory-guided decision-making. Finally, a Neurosynth meta-analysis of fMRI studies suggests new hypotheses regarding the functions of the MTN and DMN subnetworks, providing a framework to guide future research on the neural architecture of episodic memory.