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Regulation of ribosomal transcription is under tight control from environmental stimuli, and this control involves changes in the chromatin structure. The underlying mechanism of how chromatin changes in response to nutrient and energy supply in the cell is still unclear. The chromatin-remodeling complex B-WICH is involved in activating the ribosomal transcription, and we show here that knock down of the B-WICH component WSTF results in cells that do not respond to glucose. The promoter is less accessible, and RNA pol I and its transcription factors SL1/TIF-1B and RRN3/TIF-1A, as well as the proto-oncogene c-MYC and the activating deacetylase SIRT7 do not bind upon glucose stimulation. In contrast, the repressive chromatin state that forms after glucose deprivation is reversible, and RNA pol I factors are recruited. WSTF knock down results in an accumulation of the ATPase CHD4, a component of the NuRD chromatin remodeling complex, which is responsible for establishing a repressive poised state at the promoter. The TTF-1, which binds and affect the binding of the chromatin complexes, is important to control the association of activating chromatin component UBF. We suggest that B-WICH is required to allow for a shift to an active chromatin state upon environmental stimulation, by counteracting the repressive state induced by the NuRD complex.

OBJECTIVE: Anxiety and depression symptoms in epilepsy are common, impactful and under-recognized and undertreated. While prior survey data suggests equipoise among epileptologists for managing anxiety and/or depression via prescribing in the epilepsy clinic versus psychiatry referral, patient preferences are unknown and should potentially influence practice habits among epileptologists. Thus, the primary objective of this study was to determine patient preference for anxiety and/or depression prescribing by neurologists versus psychiatry referral among an adult epilepsy clinic sample of symptomatic patients. METHODS: Management preferences for anxiety and/or depression were surveyed in an adult tertiary care epilepsy clinic. Individuals who screened positive for anxiety and/or depression symptoms on validated instruments during a routine care-embedded learning health system study were recruited. Demographics, social variables, psychiatric treatment history, and treatment priorities and preferences were surveyed. Preference was defined as a slightly greater than 2:1 ratio in favor neurology prescribing or psychiatry referral. The study was powered to assess this primary objective using a two-sample binomial test. Multinomial logistic regression examined an a priori multivariable model of treatment preference (secondary objective). RESULTS: The study sample included N=63 symptomatic adults, with 64% women and mean age 42.2 years. Most reported past or current treatment for anxiety and/or depression, and treatment for these symptoms was a high or moderate priority among 65.1% of the sample. Neurologist prescribing was preferred in 83.0% (nearly 5:1) over psychiatry referral among those who chose neurology or psychiatry (as opposed to neither of the two; p

Exposure to suboptimal ambient temperature during pregnancy has been reported as a potential teratogen of fetal development. However, limited animal evidence is available regarding the impact of extreme temperatures on maternal pregnancy and the subsequent adverse pregnancy outcomes. Our objective in this study is to investigate the relationship between temperature and maternal stress during pregnancy in mice. This study used the Naval Medical Research Institute (NMRI) mice during the second and third pregnant weeks with the gestational day (GD) (GD 6.5–14.5 and GD 14.5–17.5). Mice were exposed to suboptimal ambient temperature (1 °C, 5 °C, 10 °C, 15 °C, 40 °C, 42 °C, 44 °C, 46 °C, and 48 °C for the experimental group and 23 °C for the control group) 1 h per day, 7 days a weekin each trimester. Measurements of placental development (placental weight [PW] and placental diameter [PD]) and fetal growth (fetal weight [FW] and crown-to-rump length [CRL]) between experimental and control groups were compared using analysis of variance (ANOVA). Data on the occurrence of preterm birth (PTB) and abnormalities were also collected. The results showed that exposure to both cold and heat stress in the second and third weeks of pregnancy caused significant decreases in measurements of placental development (PW and PD) and fetal growth (FW and CRL). For all temperature exposures, 15 °C was identified as the optimal temperature in the development of the embryo. Most PTB occurrences were observed in high-temperature stress groups, with the highest PTB number seen in the exposure group at 48 °C, whereas PTB occurred only at 1 °C among cold stress groups. In the selected exposure experiments, an approximate U-shaped relation was observed between temperature and number of abnormality occurrence. The highest percentage of these anomalies occurred at temperatures of 1 °C and 48 °C, while no abnormalities were observed at 15 °C and in the control group. Our findings strengthened the evidence that exposure to suboptimal ambient temperatures may trigger adverse pregnancy outcomes and worsen embryo and fetal development in mice.

Discovery of new properties and special functionalities at the nanoscale materials caused nanotechnology to become one of the leading parts in all sciences namely biology and medicine. Magnetic iron oxide nanoparticles (MIONPs) are among interesting nanomaterials in biomedical arena, which have attracted the attention of many researchers owing to their extensive capabilities. Due to the simple, cost-effective and environmentally-friendly production processes, biosynthesis is of paramount importance between different methods of nanoparticles production. In the current study, we succeeded to synthesize MIONPs using a newly extracted bacteria supernatant. Produced nanoparticles were characterized using FE-SEM, DLS, VSM, UV-vis, FT-IR and EDS spectroscopy. Analysis showed that the average particle size of very stable spherical MIONPs is about 29.3 nm. The bacteria protein profile obtained by SDS-PAGE analysis indicated induction of different proteins. In vitro cytotoxicity of nanoparticles on the viability of MCF7 and 3T3 cell lines was assessed by MTT assay. The results show that toxicity of the produced nanoparticles (IC50, MCF-7 > 5 mg/ml and IC50, 3T3 > 7.5 mg/ml) follows a concentration dependent manner.

The purpose of our manuscript is to review the current evidence supporting the use of complementary and alternative medicine (CAM) in neuromuscular disease, specifically in painful peripheral neuropathy (PPN). We outline the therapeutic challenges of this debilitating condition and describe the best evidence for incorporating such therapies into clinical practice. The most studied modalities include lifestyle modifications with diet and exercise, supplements, and acupuncture. CAM therapies such as yoga, meditation, electrical stimulation, neuromodulatory devices, and cannabis are mentioned as emerging therapies. Current data suggests that targeted lifestyle modifications, including aerobic exercise and diet modifications that promote weight loss, may improve the natural course of diabetic painful neuropathy and potentially other types of neuropathy. A number of studied dietary supplements and vitamins including B vitamins, vitamin D, alpha-lipoic acid, and acetyl-l-carnitine improve both subjective and objective neuropathic measures. A wide range of neuromodulatory devices and electrical stimulation modalities demonstrate mixed results, and further studies are needed to confirm their benefit. Finally, acupuncture and yoga both demonstrate benefit in a variety of PPNs. Multiple CAM therapies show efficacy in the treatment of PPN. From the strongest level of evidence to the least, lifestyle modifications including exercise and diet; supplements including B12, alpha lipoic acid, acetyl-l-carnitine, and vitamin D in deficient patients; followed by acupuncture and yoga may alleviate symptoms of PPN.

Lignin fractions with different molecular weight were prepared using a simple and almost green method from switchgrass and pine organosolv lignin. Different proportions of acetone in water, ranging from 30 to 60%, were used for lignin fractionation. A higher concentration of acetone dissolved higher molecular weight fractions of the lignin. Fractionated organosolv lignin showed different molecular weight and functional groups. Higher molecular weight fractions exhibited more aliphatic and less phenolic OH than lower molecular weight fractions. Lower molecular weight fractions lead to more homogeneous structure compared to samples with a higher molecular weight. All fractions showed strong antioxidant activity.

The chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. However, the underlying mechanism is unknown. Using high-resolution MN walking we demonstrate here that B-WICH changes the chromatin structure in the vicinity of the 5S rRNA and 7SL RNA genes during RNA polymerase III transcription. The action of B-WICH is required for the binding of the RNA polymerase machinery and the regulatory factors c-Myc at the 5S rRNA and 7SL RNA genes. In addition to the c-Myc binding site at the 5S genes, we have revealed a novel c-Myc and Max binding site in the intergenic spacer of the 5S rDNA. This region also contains a region remodelled by B-WICH. We demonstrate that c-Myc binds to both sites in a Max-dependent way, and thereby activate transcription by acetylating histone H3. The novel binding patterns of c-Myc and Max link transcription of 5S rRNA to the Myc/Max/Mxd network. Since B-WICH acts prior to c-Myc and other factors, we propose a model in which the B-WICH complex is required to maintain an open chromatin structure at these RNA polymerase III genes. This is a prerequisite for the binding of additional regulatory factors.

Starch nanocrystal was prepared using weak sulfuric acid hydrolysis at 40 °C. Transmission electron micrographs of dilute suspensions of starch nanocrystals showed round particles with a diameter ranging from 20 to 40 nm. SEM of freeze dried samples showed separated particles between 40 and 100 nm and confirmed production of starch nano particles. XRD patterns obtained for the prepared nanostarch and raw starch sample showed no special pattern of crystallinity for starch sample. Extracted nanostarch showed pattern of crystallinity with the peaks at Bragg angles (2θ) at about 15° and 23°, and a doublet at 17° and 18°. The crystalline structure of prepared sample was A-type. FTIR spectra confirmed the particles oxidation. Nano silver particle was precipitated on the starch nano particle. UV spectra confirmed the presence of silver particle on the starch particles. Inhibitions tests of nanostarch bearing nano silver on three types of bacteria was investigated. The inhibition test results were 25 µg/mL for S. aureus, and S. typhi, and 12.5 µg/mL for E. coli.

Actin and nuclear myosin 1c (NM1) cooperate in RNA polymerase I (pol I) transcription. NM1 is also part of a multiprotein assembly, B-WICH, which is involved in transcription. This assembly contains the chromatin remodeling complex WICH with its subunits WSTF and SNF2h. We report here that NM1 binds SNF2h with enhanced affinity upon impairment of the actin-binding function. ChIP analysis revealed that NM1, SNF2h, and actin gene occupancies are cell cycle-dependent and require intact motor function. At the onset of cell division, when transcription is temporarily blocked, B-WICH is disassembled due to WSTF phosphorylation, to be reassembled on the active gene at exit from mitosis. NM1 gene knockdown and motor function inhibition, or stable expression of NM1 mutants that do not interact with actin or chromatin, overall repressed rRNA synthesis by stalling pol I at the gene promoter, led to chromatin alterations by changing the state of H3K9 acetylation at gene promoter, and delayed cell cycle progression. These results suggest a unique structural role for NM1 in which the interaction with SNF2h stabilizes B-WICH at the gene promoter and facilitates recruitment of the HAT PCAF. This leads to a permissive chromatin structure required for transcription activation., Author Summary Actin and myosin are key regulators of several processes that occur in the cell nucleus. In rRNA biogenesis, actin in complex with nuclear myosin 1c (NM1) is involved in several phases of rDNA transcription. Further, NM1 interacts with the chromatin remodelling complex WICH, with the subunits WSTF and SNF2h. The multiprotein assembly thus formed, termed B-WICH, is engaged in the post-initiation phase of pol I transcription. These observations have led to the proposal that the actin-NM1 interaction mediates the recruitment of the WICH complex to activate transcription. Recent evidence indicates that the WSTF component of the B-WICH complex facilitates SNF2h-dependent nucleosomes repositioning and remodels in this way the chromatin at the rRNA gene promoter. We show here that NM1 interacts with the WICH complex and that this interaction is required to establish permissive chromatin by promoting H3K9 acetylation. This mechanism leads to transcription activation and facilitates cell cycle progression. NM1 performs these actions by interacting with SNF2h, presumably stabilizing B-WICH at the gene promoter. We show also that NM1 is needed for association of the polymerase-associated actin with the rRNA gene. Actin and SNF2h compete for NM1 binding. Therefore we propose a two-step mechanism of gene activation where NM1 functions as a structural switch that connects pol I with chromatin for transcription activation and cell cycle progression.

The phenylanine-glycine (FG)–rich regions of several nucleoporins both bind to nuclear transport receptors and collectively provide a diffusion barrier to the nuclear pores. However, the in vivo roles of FG nucleoporins in transport remain unclear. We have inactivated 30 putative nucleoporins in cultured Drosophila melanogaster S2 cells by RNA interference and analyzed the phenotypes on importin α/β−mediated import and CRM1-dependent protein export. The fly homologues of FG nucleoporins Nup358, Nup153, and Nup54 are selectively required for import. The FG repeats of Nup153 are necessary for its function in transport, whereas the remainder of the protein maintains pore integrity. Inactivation of the CRM1 cofactor RanBP3 decreased the nuclear accumulation of CRM1 and protein export. We report a surprisingly antagonistic relationship between RanBP3 and the Nup214 FG region in determining CRM1 localization and its function in protein export. Our data suggest that peripheral metazoan FG nucleoporins have distinct functions in nuclear protein transport events.