Distinct functions of the Drosophila Nup153 and Nup214 FG domains in nuclear protein transport

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

Forecasting Schizophrenia Incidence Frequencies Using Time Series Approach

Introduction: Understanding the prevalence of schizophrenia has important implications for both health service planning and risk factor epidemiology. The aims of this study are to systematically identify and collate studies describing the prevalence of schizophrenia, to summarize the findings of these studies, and to explore selected factors that may influence prevalence estimates.Methods: This historical cohort study was done on schizophrenia patients in Farshchian psychiatric hospital from April 2008 to April 2016. To analyze the data, the Holt-Winters Exponential Smoothing (HWES) method was applied. All the analyses were done by R.3.2.3. Software using the packages “forecast” and “tseries”. The statistical significant level was assumed as 0.05.Results: Our investigation show that a constant frequency of Schizophrenia incidence happens every month from August 2008 to February 2015 while a considerable increase occurs in March 2015. The high frequency of Schizophrenia incidence remains constant to the end of 2015 and a decrease is shown in 2016. Also, data demonstrate the development of Schizophrenia in the next 24 months with 95% confidence interval.Conclusion: Our study showed that a significant increase happens in the frequency of Schizophrenia from 2016. Although the development is not constant and the same for all months, the amount of increase is considerably high comparing to before 2016.

The Chromatin Remodelling Complex B-WICH Changes the Chromatin Structure and Recruits Histone Acetyl-Transferases to Active rRNA Genes

The chromatin remodelling complex B-WICH, which comprises the William syndrome transcription factor (WSTF), SNF2h, and nuclear myosin 1 (NM1), is involved in regulating rDNA transcription, and SiRNA silencing of WSTF leads to a reduced level of 45S pre-rRNA. The mechanism behind the action of B-WICH is unclear. Here, we show that the B-WICH complex affects the chromatin structure and that silencing of the WSTF protein results in a compaction of the chromatin structure over a 200 basepair region at the rRNA promoter. WSTF knock down does not show an effect on the binding of the rRNA-specific enhancer and chromatin protein UBF, which contributes to the chromatin structure at active genes. Instead, WSTF knock down results in a reduced level of acetylated H3-Ac, in particular H3K9-Ac, at the promoter and along the gene. The association of the histone acetyl-transferases PCAF, p300 and GCN5 with the promoter is reduced in WSTF knock down cells, whereas the association of the histone acetyl-transferase MOF is retained. A low level of H3-Ac was also found in growing cells, but here histone acetyl-transferases were present at the rDNA promoter. We propose that the B-WICH complex remodels the chromatin structure at actively transcribed rRNA genes, and this allows for the association of specific histone acetyl-transferases

The anti-bacterial effects of magnetic iron oxide nanoparticles produced by biological method and the kinetic study of mortality of common strains in clinical infections

New properties of nano-materials have made nanotechnology the leading part of biology and medical sciences. Due to their various biomedical properties, iron-based magnetic nanoparticles (MNPs) have been highly considered by biological researchers. Nowadays, increasing resistance to antibiotics is a major problem in treating clinical infections. Finding new antibacterial agents is therefore essential for the treatment of resistant strains. In this study, the iron oxide MNPs were produced using culture-medium supernatant of a newly isolated bacterium to investigate the inhibitory effects of the NPs on strains with a major role in clinical infections. Biosynthesis of iron oxide MNPs were detected by UV-Vis spectroscopy and the average size of particles was estimated by dynamic light scattering technique. The anti-bacterial activity of these NPs against E. coli and S. aureus was investigated using methods for the calculation of bacterial sensitivity coefficient. In the presence of NPs, the highest sensitivity coefficient value was observed for E. coli in 1xMIC concentration. On the other hand, S. aureus showed the lowest value. The death rate of the two strains in contact with NPs followed the first order kinetic equation and the survival rate decreased with the increase of exposure time. The results of this study as well as the high functionality of iron oxide MNPs, make its application desirable in the prevention and treatment of clinical infections

Prioritizing the Factors Affecting Job Satisfaction among Hospitals Staff Affiliated to Tehran University of Medical Sciences Based on Analytic Hierarchy Process

Introduction: Challenges of service provision systems necessitate the presence of staff with higher motivation to work more efficiently; therefore, paying close attention to job satisfaction of such staffs to enhance organizational efficiency sounds essential. This study aimed to prioritize factors affecting personnel satisfaction in hospitals of TUMS using AHP Model.   Materials & Methods: This was a cross-sectional study conducted in 5 hospitals affiliated to Tehran University of Medical Sciences in 2015. The data collection tool was a questionnaire containing demographic questions as well as nine questions on personnel satisfaction. The validity and reliability of the questionnaire were assessed, and the data was analyzed using analytic hierarchy process and Expert Choice V. 11 software.   Findings: According to the AHP model, rewards and compensations were the most important factors (0.262), and monitoring and supervision were of the lowest importance (0.030). Factors of Job security (0.182), job improvement (0.177), job positions (0.091), working conditions (0.075), communications among colleagues (0.063), associated with personal life (0.060), and policy management (0.035) obtained next priority. Also, rank of items in unmarried female employees were higher than that of married male employees.   Discussion & Conclusion: The conclusions for our investigation demonstrate that correction mechanisms in hospitals and use of leverage by offering incentives such as performance-based management can enhance motivation as well as the employees’ performances. In addition, efforts to strengthen social relationships among colleagues would lead to more satisfaction as a significant component

Nuclear Myosin 1c Facilitates the Chromatin Modifications Required to Activate rRNA Gene Transcription and Cell Cycle Progression

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.AuthorCount:10;</p

A speculative two-step model in which NM1 bridges the pol I machinery and chromatin <i>via</i> an interaction with SNF2h that competes with actin.

<p>(I) NM1 interacts with polymeric actin and with the rDNA <i>via</i> its C-terminus, generating local force that pulls the polymerase along active gene. (II) Upon NM1 dissociation from actin, NM1 interacts with SNF2h in a WSTF-dependent manner, a mechanism that provides a way to stabilize the WICH complex on the rDNA, to recruit PCAF, and to maintain the levels of H3K9 acetylation required for transcription activation.</p

A functional NM1 is required for the activation of pol I transcription.

<p>(A) RNAi-mediated NM1 gene knockdown in HeLa cells analyzed by double immunostaining and confocal microscopy with antibodies to NM1 and fibrillarin, after transfection of NM1-specific siRNA or control oligos (scrRNAi). Scale bars, 5 µm. (B) Steady state expression levels for NM1, WSTF, SNF2h and actin monitored on immunoblots of total lysates prepared from HeLa cells subjected to NM1 gene knockdown (NM1 RNAi) or from cells subjected to scrRNAi. (C) Semiquantitative densitometric quantification of NM1 steady state protein expression relative to actin. (D) qRT-PCR analysis of 45S pre-rRNA performed on total RNA prepared from HeLa cells subjected to NM1 gene knockdown (NM1 RNAi) or from cells subjected to control siRNA oligonucleotides (scrRNAi). The 45S pre-rRNA levels are relative to GAPDH mRNA. (E–F) FUrd incorporation assays on living HeLa cells subjected to (E) NM1 gene knockdown by RNAi, or (F) treated with BDM. Transcription was monitored by short FUrd pulses to follow incorporation into nascent nucleolar transcripts. Quantification of the FUrd foci after immunostaining and confocal microscopy was performed by measurements on randomly selected nucleolar regions in the images. The signal was quantified using ImageJ software. The average of the mean grey values in control cells was determined, and defined as hundred percent of signal. The average of the mean grey values measured after treatment was expressed proportionally. n = number of cells in each experiment. Error bars represent standard deviations. (G) rRNA synthesis in HEK293T cells stably expressing V5-wtNM1, V5-RK605AA, V5-ΔC or V5-ΔIQ NM1 mutants. For the analysis, relative 45S pre-rRNA levels were monitored from total RNA preparations by RT–qPCR using GAPDH mRNA as internal control. Error bars represent the standard deviation of three independent experiments. Significances [<i>p</i>_{RK605AA NM1} = 0.019 (*), <i>p</i>_{ΔC NM1} = 0.0006 (***), <i>p</i>_{ΔIQ NM1} = 0.05 (*)] were obtained by Student's T-test, two-sample, equal variance.</p