The Discussion on Fire problems of large urban complexes and Countermeasures

The fire danger in large urban complexes and fire problems for design review and daily supervision to bring proposed targeted countermeasures for future large-scale urban complex design review and supervision to provide an effective solution methods and measures

Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and amyotrophic lateral sclerosis

IntroductionAmyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood pathophysiology. Recent studies have highlighted systemic inflammation, especially the role of circulating inflammatory proteins, in ALS.MethodsThis study investigates the potential causal link between these proteins and ALS. We employed a two-sample Mendelian Randomization(MR) approach, analyzing data from large-scale genome-wide association studies to explore the relationship between 91 circulating inflammatory proteins and ALS. This included various MR methods like MR Egger, weighted median, and inverse-variance weighted, complemented by sensitivity analyses for robust results.ResultsSignificant associations were observed between levels of inflammatory proteins, including Adenosine Deaminase, Interleukin-17C, Oncostatin-M, Leukemia Inhibitory Factor Receptor, and Osteoprotegerin, and ALS risk. Consistencies were noted across different P-value thresholds. Bidirectional MR suggested that ALS risk might influence levels of certain inflammatory proteins.DiscussionOur findings, via MR analysis, indicate a potential causal relationship between circulating inflammatory proteins and ALS. This sheds new light on ALS pathophysiology and suggests possible therapeutic targets. Further research is required to confirm these results and understand the specific roles of these proteins in ALS

Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins

ABSTRACT Primary human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimers [(gp120/gp41)3] typically exist in a metastable closed conformation (state 1). Binding the CD4 receptor triggers Env to undergo extensive conformational changes to mediate virus entry. We identified specific gp120 residues that restrain Env in state 1. Alteration of these restraining residues destabilized state 1, allowing Env to populate a functional conformation (state 2) intermediate between state 1 and the full CD4-bound state (state 3). Increased state 2 occupancy was associated with lower energy barriers between the states. State 2 was an obligate intermediate for all transitions between state 1 and state 3. State 2-enriched Envs required lower CD4 concentrations to trigger virus entry and more efficiently infected cells expressing low levels of CD4. These Envs were resistant to several broadly neutralizing antibodies and small-molecule inhibitors. Thus, state 2 is an Env conformation on the virus entry pathway; sampling state 2 increases the adaptability of HIV-1 to different host cell receptor levels and immune environments. Our results provide new insights into the conformational regulation of HIV-1 entry

Cerebral activity to opposite-sex voices reflected by event-related potentials.

Human voice is a gender discriminating cue and is important to mate selection. This study employed electrophysiological recordings to examine whether there is specific cerebral activity when presented with opposite-sex voices as compared to same-sex voices. Male voices and female voices were pseudo-randomly presented to male and female participants. In Experiment 1, participants were instructed to determine the gender of each voice. A late positivity (LP) response around 750 ms after voice onset was elicited by opposite-sex voices, as reflected by a positive deflection of the ERP to opposite-sex voices than that to same-sex voices. This LP response was prominent around parieto-occipital recording sites, and it suggests an opposite-sex specific process, which may reflect emotion- and/or reward-related cerebral activity. In Experiment 2, participants were instructed to press a key when hearing a non-voice pure tone and not give any response when they heard voice stimuli. In this task, no difference were found between the ERP to same-sex voices and that to opposite-sex voices, suggesting that the cerebral activity to opposite-sex voices may disappear without gender-related attention. These results provide significant implications on cognitive mechanisms with regard to opposite-sex specific voice processing

Is the Excessive Use of Microblogs an Internet Addiction? Developing a Scale for Assessing the Excessive Use of Microblogs in Chinese College Students

<div><p>More and more college students are using microblogs, with some excessive users demonstrating addiction-like symptoms. However, there is currently no published scale available for use in assessing excessive use of these microblogs, a significant impediment to advancing this area of research. We collected data from 3,047 college students in China and developed a Microblog Excessive Use Scale (MEUS) for Chinese college students, comparing it with criteria used for assessing Internet addiction. Our diagnostic scale featured three factors, two of which–“withdrawal and health problem” and “time management and performance”–are already included in Internet addiction assessment scales. The third factor, “social comfort,” does not appear in Internet addiction assessment scales. Our study found that females have significantly higher MEUS scores than males, and that total MEUS scores positively correlated with scores from “self-disclosure” and “real social interaction” scales. These findings differ from results obtained in previous investigations into Internet addiction. Our results indicate that some characteristics of the excessive use of microblogs are different to those of Internet addiction, suggesting that microblog overuse may not correspond exactly to the state of Internet addiction.</p></div

The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions

The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally “closed” State 1 to more “open” conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 β20–β21 element as a major regulator of Env transitions. Several amino acid changes in the β20–β21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry

Sound waveforms.

<p>Two representative exemplars of the 9 male voices and 9 female voices were illustrated. The consonant part (/h-/) of the sound was normalized at around 40 ms in duration and the whole sound was normalized at 300 ms in duration.</p

Electrical Stimulation over Bilateral Occipito-Temporal Regions Reduces N170 in the Right Hemisphere and the Composite Face Effect

<div><p>Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical excitability. Although the clinical value of tDCS has been advocated, the potential of tDCS in cognitive rehabilitation of face processing deficits is less understood. Face processing has been associated with the occipito-temporal cortex (OT). The present study investigated whether face processing in healthy adults can be modulated by applying tDCS over the OT. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115772#s2" target="_blank">Experiment 1</a> investigated whether tDCS can affect N170, a face-sensitive ERP component, with a face orientation judgment task. The N170 in the right hemisphere was reduced in active stimulation conditions compared with the sham stimulation condition for both upright faces and inverted faces. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115772#s3" target="_blank">Experiment 2</a> further demonstrated that tDCS can modulate the composite face effect, a type of holistic processing that reflects the obligatory attention to all parts of a face. The composite face effect was reduced in active stimulation conditions compared with the sham stimulation condition. Additionally, the current polarity did not modulate the effect of tDCS in the two experiments. The present study demonstrates that N170 can be causally manipulated by stimulating the OT with weak currents. Furthermore, our study provides evidence that obligatory attention to all parts of a face can be affected by the commonly used tDCS parameter setting.</p></div