Pioneer Factor NeuroD1 Rearranges Transcriptional and Epigenetic Profiles to Execute Microglia-Neuron Conversion

1. Download high-res image (261KB)
2. Download full-size image

     

Human Brown Adipose Tissue Depots Automatically Segmented by Positron Emission Tomography/Computed Tomography and Registered Magnetic Resonance Images

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in humans. Detecting BAT is typically confirmed by the uptake of the injected radioactive tracer ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) into adipose tissue depots, as measured by positron emission tomography/computed tomography (PET-CT) scans after exposing the subject to cold stimulus. Fat-water separated magnetic resonance imaging (MRI) has the ability to distinguish BAT without the use of a radioactive tracer. To date, MRI of BAT in adult humans has not been co-registered with cold-activated PET-CT. Therefore, this protocol uses ¹⁸F-FDG PET-CT scans to automatically generate a BAT mask, which is then applied to co-registered MRI scans of the same subject. This approach enables measurement of quantitative MRI properties of BAT without manual segmentation. BAT masks are created from two PET-CT scans: after exposure for 2 hr to either thermoneutral (TN) (24 °C) or cold-activated (CA) (17 °C) conditions. The TN and CA PET-CT scans are registered, and the PET standardized uptake and CT Hounsfield values are used to create a mask containing only BAT. CA and TN MRI scans are also acquired on the same subject and registered to the PET-CT scans in order to establish quantitative MRI properties within the automatically defined BAT mask. An advantage of this approach is that the segmentation is completely automated and is based on widely accepted methods for identification of activated BAT (PET-CT). The quantitative MRI properties of BAT established using this protocol can serve as the basis for an MRI-only BAT examination that avoids the radiation associated with PET-CT.     

Mildew of oleaster (Elaeagnus oxycarpa Schlecht.) registered in large industrial cities (Pavlodar,Aksu, Ekibastuz) of the Pavlodar region

Purpose: Vegetation plays a very important role in industrial regions in terms of not only air purification, but also oxygen enrichment, air humidity, and city aesthetics. The paper presents the authors’ study of oleaster mildew during 2012–2013 in the cities of Pavlodar, Ekibastuz, and Aksu. Method: The species composition of mildew, patterns of its growth and reproduction, seasonal dynamics, and the level of trees infection according to a six-score scale were determined. Result: Three cultivars of mildew from three genera were registered. The species composition of mildew of oleaster is studied for the first time in large industrial cities of the Pavlodar region. The comparative analysis of the systematic structure of phytopathogenic fungi was followed by the study of the micro flora of green planting in megalopolises. The seasonal dynamics of growth, development, and reproduction was determined. The impact of pests on host-plants was studied. Conclusion: Timely diagnosis and localization of disease outbreak increases the likelihood of successful treatment and saving of plants.     

Adenine and guanine recognition of stop codon is mediated by different N domain conformations of translation termination factor eRF1

Positioning of release factor eRF1 toward adenines and the ribose-phosphate backbone of the UAAA stop signal in the ribosomal decoding site was studied using messenger RNA (mRNA) analogs containing stop signal UAA/UAAA and a photoactivatable cross-linker at definite locations. The human eRF1 peptides cross-linked to these analogs were identified. Cross-linkers on the adenines at the 2nd, 3rd or 4th position modified eRF1 near the conserved YxCxxxF loop (positions 125-131 in the N domain), but cross-linker at the 4th position mainly modified the tripeptide 26-AAR-28. This tripeptide cross-linked also with derivatized 3'-phosphate of UAA, while the same cross-linker at the 3'-phosphate of UAAA modified both the 26-28 and 67-73 fragments. A comparison of the results with those obtained earlier with mRNA analogs bearing a similar cross-linker at the guanines indicates that positioning of eRF1 toward adenines and guanines of stop signals in the 80S termination complex is different. Molecular modeling of eRF1 in the 80S termination complex showed that eRF1 fragments neighboring guanines and adenines of stop signals are compatible with different N domain conformations of eRF1. These conformations vary by positioning of stop signal purines toward the universally conserved dipeptide 31-GT-32, which neighbors guanines but is oriented more distantly from adenines.     

Looking the part: social status cues shape race perception

It is commonly believed that race is perceived through another's facial features, such as skin color. In the present research, we demonstrate that cues to social status that often surround a face systematically change the perception of its race. Participants categorized the race of faces that varied along White-Black morph continua and that were presented with high-status or low-status attire. Low-status attire increased the likelihood of categorization as Black, whereas high-status attire increased the likelihood of categorization as White; and this influence grew stronger as race became more ambiguous (Experiment 1). When faces with high-status attire were categorized as Black or faces with low-status attire were categorized as White, participants' hand movements nevertheless revealed a simultaneous attraction to select the other race-category response (stereotypically tied to the status cue) before arriving at a final categorization. Further, this attraction effect grew as race became more ambiguous (Experiment 2). Computational simulations then demonstrated that these effects may be accounted for by a neurally plausible person categorization system, in which contextual cues come to trigger stereotypes that in turn influence race perception. Together, the findings show how stereotypes interact with physical cues to shape person categorization, and suggest that social and contextual factors guide the perception of race.     

Targeting key transcriptional factor STAT3 in colorectal cancer

Molecular and Cellular Biochemistry - In developed countries, colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of malignant-related deaths. CRC is treatable...     

Distribution of heavy metals in the water,sediments, and fishes from Damodar river basin at steel city,India: a probabilistic risk assessment

Abstract

The present study, deals with the estimation of degrees of contamination, ecological and human health risk of heavy metals (As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn) in sediments, surface water and fishes, which were collected from middle stretch of Damodar river and ponds at Asansol, which receives outfall of various coal-based industries. Metal content in the premonsoon season was higher than the postmonsoon, due to influx of rainwater. The heavy metal pollution indices (HPI) at some locations was observed up to 1.45 times than recommended value and the cadmium (Cd) was found dominating metal for high HPI value. The Cd concentration in surface water and pore water varied from 2.8 to 14.9?µg/L and 15.3–57.0?µg/L, respectively, which was up to 6 times higher than the permissible limit. Ecological risk assessment for sediments illustrates ‘moderate to considerable ecological risk’, especially because of Cd. Hazard index (HI) calculated to identify potential human health risk by dermal exposure of surface water was <0.1, indicating ‘negligible non-cancer risk’ for all age group of people. However, HI varied from 0.73 to 1.49 for adult and 1.37–2.78 by consumption of fishes indicates children have higher ‘non-cancer risk’ than adult.     

Amino-terminal Cysteine Residues Differentially Influence RGS4 Protein Plasma Membrane Targeting, Intracellular Trafficking, and Function

Regulator of G-protein signaling (RGS) proteins are potent inhibitors of heterotrimeric G-protein signaling. RGS4 attenuates G-protein activity in several tissues. Previous work demonstrated that cysteine palmitoylation on residues in the amino-terminal (Cys-2 and Cys-12) and core domains (Cys-95) of RGS4 is important for protein stability, plasma membrane targeting, and GTPase activating function. To date Cys-2 has been the priority target for RGS4 regulation by palmitoylation based on its putative role in stabilizing the RGS4 protein. Here, we investigate differences in the contribution of Cys-2 and Cys-12 to the intracellular localization and function of RGS4. Inhibition of RGS4 palmitoylation with 2-bromopalmitate dramatically reduced its localization to the plasma membrane. Similarly, mutation of the RGS4 amphipathic helix (L23D) prevented membrane localization and its G(q) inhibitory function. Together, these data suggest that both RGS4 palmitoylation and the amphipathic helix domain are required for optimal plasma membrane targeting and function of RGS4. Mutation of Cys-12 decreased RGS4 membrane targeting to a similar extent as 2-bromopalmitate, resulting in complete loss of its G(q) inhibitory function. Mutation of Cys-2 did not impair plasma membrane targeting but did partially impair its function as a G(q) inhibitor. Comparison of the endosomal distribution pattern of wild type and mutant RGS4 proteins with TGN38 indicated that palmitoylation of these two cysteines contributes differentially to the intracellular trafficking of RGS4. These data show for the first time that Cys-2 and Cys-12 play markedly different roles in the regulation of RGS4 membrane localization, intracellular trafficking, and G(q) inhibitory function via mechanisms that are unrelated to RGS4 protein stabilization.     

Delayed sleep phase disorder and Attention deficit and hyperactivity symptoms in a teenager

JR is an 18-year-old male with five-year history of going to bed late and waking up late. He gives history of poor frustration tolerance, inattention and fidgetiness in school for which he has been unsuccessfully been treated with stimulant medications for last 3 years. There is history of similar sleep problems in his father who works nights as a mechanic. JR's sleep log shows him going to bed early morning and waking up late morning/afternoon. He shows no sleep maintenance problems and sleeps an average of 8 h per night. He shows no symptoms of depression, anxiety, inattention or hyperactivity during his hospital stay. He does not show any learning, cognitive, attention or intellectual deficits. He is currently not taking any medications. He is discharged home after 3-day hospital stay and is reportedly doing well working in a video rental store at night.     

Histone modifications dictate specific biological readouts

The basic unit of chromatin is the nucleosomal core particle, containing 147 bp of DNA that wraps twice around an octamer of core histones. The core histones bear a highly dynamic N-terminal amino acid tail around 20-35 residues in length and rich in basic amino acids. These tails extending from the surface of nucleosome play an important role in folding of nucleosomal arrays into higher order chromatin structure, which plays an important role in eukaryotic gene regulation. The amino terminal tails protruding from the nuclesomes get modified by the addition of small groups such as methyl, acetyl and phosphoryl groups. In this review, we focus on these complex modi- fication patterns and their biological functions. Moreover, these modifications seem to be part of a complex scheme where distinct histone modifications act in a sequential manner or in combination to form a ＂histone code＂ read by other proteins to control the structure and/or function of the chromatin fiber. Errors in this histone code may be involved in many human diseases especially cancer, the nature of which could be therapeutically exploited. Increasing evidence suggests that many proteins bear multiple, distinct modifications, and the ability of one modification to antagonize or synergize the deposition of another can have significant biological consequences.