Braswellmcgowan9188
When subtracting measurements during resting state from measurements during MNS, neither functional oxy-Hb nor deoxy-Hb changes could be recovered while SEPs remained unchanged. In conclusion, Valsalva-induced eICP prevents oxy-Hb and deoxy-Hb changes during neuronal activation in SI. This finding raises questions on the validity of oxy-Hb- and deoxy-Hb-based brain imaging (e.g., BOLD-fMRI) during eICP. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of the mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular-targeting drug delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multi-functional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli-responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this review, we surveyed the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria-targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondria-targeting nanotherapeutics. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The biochemical functions of proteins are activated at the protein glass transition temperature, which has been proposed to be dependent upon protein-water interactions. However, at the molecular level it is unclear how ligand binding to well-defined binding sites can influence this transition temperature. We thus report molecular dynamics (MD) simulations of the ε subunit from thermophilic Bacillus PS3 in the ATP-free and ligand-bound states over a range of temperatures from 20 to 300 K, to study the influence of ligand association upon the transition temperature. We also measure the protein mean square displacement (MSD) in each state, which is well established as a means to quantify this dynamical temperature dependence. We find that the transition temperature is largely unaffected by ligand association, but the MSD beyond the transition temperature increases more rapidly in the ATP-free state. Our data suggests that ligands can effectively "shield" a binding site from solvent, and hence stabilize protein domains with increasing temperature. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The default mode network (DMN) is a network of brain regions that is activated while we are not engaged in any particular task. While there is a large volume of research documenting functional connectivity within the DMN in adults, knowledge of the development of this network is still limited. CAY10585 There is some evidence for a gradual increase in the functional connections within the DMN during the first 2 years of life, in contrast to other functional resting-state networks that support primary sensorimotor functions, which are online from very early in life. Previous studies that investigated the development of the DMN acquired data from sleeping infants using fMRI. However, sleep stages are known to affect functional connectivity. In the current longitudinal study, fNIRS was used to measure spontaneous fluctuations in connectivity within fronto-temporoparietal areas-as a proxy for the DMN-in awake participants every 6 months from 11 months till 36 months. This study validates a method for recording resting-state data from awake infants, and presents a data analysis pipeline for the investigation of functional connections with infant fNIRS data, which will be beneficial for researchers in this field. A gradual development of fronto-temporoparietal connectivity was found, supporting the idea that the DMN develops over the first years of life. Functional connectivity reached its maximum peak at about 24 months, which is consistent with previous findings showing that, by 2 years of age, DMN connectivity is similar to that observed in adults. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.Flame retardants, specifically polybrominated diphenyl ethers (PBDEs), are chemical compounds widely used for industrial purposes and household materials. NHANES data indicate that nearly all Americans have trace amounts of PBDEs in serum, with even higher levels associated with occupational exposure. PBDEs are known to bioaccumulate in the environment due to their lipophilicity and stability, and more importantly, they have been detected in human adipose tissue. The present study examined whether the PBDE congener, BDE-99 (2,2',4,4',5-pentabromodiphenyl ether; 0.2-20 μM), enhances the adipogenesis of mouse and human preadipocyte cell models in vitro via induced lipid accumulation. 3T3-L1 mouse preadipocytes and human visceral preadipocytes demonstrated enhanced hormone-induced lipid accumulation upon BDE-99 treatment. In addition, BDE-99 (20 μM) induced preadipocyte differentiation and lipid development in nondifferentiated human preadipocytes. BDE-99, the second most abundant congener in human adipose tissue, increased total lipids in differentiating adipocytes and therefore showed a potential role in the regulation of adipogenesis. This warrants more research to further understand the impact of lipophilic persistent pollutants on adipose tissue homeostasis. © 2020 Wiley Periodicals, Inc.OBJECTIVES The impact of religion/spirituality (R/S) on cancer outcomes, including health-related quality of life (HRQoL), has been the topic of much investigation. Reports of the opposite, i.e., the impact of cancer on R/S and associations with HRQoL, are few. The current study sought to explore the positive and negative impacts of cancer on the religious faith of survivors as well as the associations of such impacts with HRQoL. METHODS Participants included 2309 9-year survivors of cancer from the American Cancer Society's Studies of Cancer Survivors - I. The impact of cancer on R/S was measured using items from the PROMIS Psychosocial Impact of Illness - Faith, and HRQoL was measured with the SF-12. Hierarchical regressions were used to examine the impact of cancer on R/S controlling for medical and demographic covariates. RESULTS Consistent with hypotheses, the majority of survivors (70%) reported that cancer had a positive impact on religious faith, while the negative impact of cancer on religious faith was relatively rare (17%). In multivariable models, the negative impact of cancer on faith was associated with poorer HRQoL, both mental and physical, while the positive impact of cancer on faith was associated with greater mental well-being. CONCLUSIONS Cancer has a negative impact on religious faith for a minority of survivors. However, when it is reported, such negative impact is indicative of poorer mental and physical well-being. As such, it is important to identify those survivors at risk early in survivorship and provide support and intervention as needed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Fresh fruits and vegetables have numerous benefits to human health. Unfortunately, their consumption is increasingly associated with food-borne diseases, Salmonella enterica being their most frequent cause in Europe. Agricultural soils were postulated as reservoir of human pathogens, contributing to the contamination of crops during the growing period. Since the competition with the indigenous soil microbiota for colonization sites plays a major role in the success of invading species, we hypothesized that reduced diversity will enhance the chance of Salmonella to successfully establish in agricultural environments. We demonstrated that the abundance of Salmonella drastically decreased in soil with highly diverse indigenous prokaryotic community, while in soil with reduced prokaryotic diversity, Salmonella persisted for a long period. Furthermore, in communities with low diversity, Salmonella had an impact on the abundance of other taxa. The high physiological plasticity allows Salmonella to use agricultural soils as alternative habitat which might provide a route of animal/human infections. In addition, adjusted transcriptional profile with amino acid biosynthesis and the glyoxylate cycle most prominently regulated, suggests an adaptation to the soil environment. Our results underline the importance of the maintenance of diverse soil microbiome as a part of strategy aiming at reduced risk of food-borne salmonellosis outbreaks. © 2020 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.Wiedemann-Steiner syndrome (WWS) is a rare disorder characterized by hypotonia, postnatal growth restriction, striking facial dysmorphism, and hirsutism. It is caused by heterozygous pathogenic variants in KMT2A. This gene has an established role in histone methylation, which explains the overlap of WWS with syndromes caused by genes involved in chromatin remodeling. We describe an infant with a novel single base pair deletion in KMT2A with features consistent with WWS, as well as additional features of stenosis of aqueduct of Sylvius and broad toes. The usefulness of Face2Gene as a tool for identification of dysmorphology syndromes is discussed, as in this patient, it suggested WWS as the top candidate disorder. To the best of our knowledge, this is the first patient of WWS reported from India, with a novel genotype and expanded phenotype. © 2020 Wiley Periodicals, Inc.Mother-to-child transmission of hepatitis B virus can occur during the intrauterine, antenatal and postnatal periods, with an increased risk of perinatal transmission. Appropriate management of patients who are hepatitis B surface antigen positive during pregnancy can substantially reduce the rates of perinatal transmission. Herein, two pregnant women with chronic hepatitis B are presented; one became pregnant while receiving tenofovir disoproxil fumarate and continued the treatment during pregnancy, the other discontinued tenofovir disoproxil fumarate treatment on her own due to conception, but restarted at 26 weeks of pregnancy. link2 At birth the newborns of both women were vaccinated and immunoglobulin was given, with no perinatal transmission. Whether pregnant women should receive antiviral therapy or immunoprophylaxis still remains controversial. In order to keep the mother's liver stable and to prevent perinatal transmission, it is of paramount importance to manage pregnant women in line with the current information and guidelines. © 2020 Japan Society of Obstetrics and Gynecology.Peptides have shown great potential in acting as template for developing versatile carrier platforms in nanomedicine, aimed at selective delivery of drugs to only pathological tissues saving its normal neighbors. link3 Cell-penetrating peptides (CPPs) are short oligomeric peptides capable of translocating across the cell membrane while simultaneously employing multiple mechanisms of entry. Most CPPs exist as disordered structures in solution and may adopt a helical conformation on interaction with cell membrane, vital to their penetrative capability. Herein, we report a series of cationic helical amphipathic peptides (CHAPs), which are topologically constrained to be helical. The peptides were tested against cervical and breast cancer cells for their cell penetration and drug delivery potential. The cellular uptake of CHAP peptides is independent of temperature and energy availability. The activity of the peptides is biocompatible in bovine serum. CHAPs delivered functional methotrexate (MTX) inside the cell as CHAP-MTX conjugates.