Identifying Tmem59 related gene regulatory network of mouse neural stem cell from a compendium of expression profiles

<p>Abstract</p> <p>Background</p> <p>Neural stem cells offer potential treatment for neurodegenerative disorders, such like Alzheimer's disease (AD). While much progress has been made in understanding neural stem cell function, a precise description of the molecular mechanisms regulating neural stem cells is not yet established. This lack of knowledge is a major barrier holding back the discovery of therapeutic uses of neural stem cells. In this paper, the regulatory mechanism of mouse neural stem cell (NSC) differentiation by <it>tmem59 </it>is explored on the genome-level.</p> <p>Results</p> <p>We identified regulators of <it>tmem59 </it>during the differentiation of mouse NSCs from a compendium of expression profiles. Based on the microarray experiment, we developed the parallelized SWNI algorithm to reconstruct gene regulatory networks of mouse neural stem cells. From the inferred <it>tmem59 </it>related gene network including 36 genes, <it>pou6f1 </it>was identified to regulate <it>tmem59 </it>significantly and might play an important role in the differentiation of NSCs in mouse brain. There are four pathways shown in the gene network, indicating that <it>tmem59 </it>locates in the downstream of the signalling pathway. The real-time RT-PCR results shown that the over-expression of <it>pou6f1 </it>could significantly up-regulate <it>tmem59 </it>expression in C17.2 NSC line. 16 out of 36 predicted genes in our constructed network have been reported to be AD-related, including <it>Ace</it>, <it>aqp1</it>, <it>arrdc3</it>, <it>cd14</it>, <it>cd59a</it>, <it>cds1</it>, <it>cldn1</it>, <it>cox8b</it>, <it>defb11</it>, <it>folr1</it>, <it>gdi2</it>, <it>mmp3</it>, <it>mgp</it>, <it>myrip</it>, <it>Ripk4</it>, <it>rnd3</it>, and <it>sncg</it>. The localization of <it>tmem59 </it>related genes and functional-related gene groups based on the Gene Ontology (GO) annotation was also identified.</p> <p>Conclusions</p> <p>Our findings suggest that the expression of <it>tmem59 </it>is an important factor contributing to AD. The parallelized SWNI algorithm increased the efficiency of network reconstruction significantly. This study enables us to highlight novel genes that may be involved in NSC differentiation and provides a shortcut to identifying genes for AD.</p

Tunable single photon and two-photon emission in a four-level quantum dot-bimodal cavity system

We investigate the generation of single photons and photon pairs in a cavity quantum electrodynamics system of a four-level quantum dot coupled to bimodal cavity. By tuning frequencies and intensity ratio of the driving lasers, sub-Poissonian and super-Poissonian photon statistics are obtained in each nondegenerate cavity mode respectively. Single photon emission is characterized as zero-delay second-order correlation function g^2(0)~0.15. Photon pair emission under the two-photon resonance excitation is quantified by Mandel parameter as Q~0.04. The mean cavity photon number in both scenarios can maintain large around 0.1. As a result, single photon emission and two-photon emission can be integrated in our proposed system only by tuning the external parameters of the driving lasers.Comment: 6 pages, 5 figure

Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma

OBJECTIVE: Increased expression of suppressor of zest 12 (SUZ12), a core component of the polycomb repressive complex 2, contributes to human tumorigenesis and associates with patient prognosis. In the present study, we sought to investigate the expression of SUZ12 and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC). METHODS: The expression of SUZ12 protein was determined by immunohistochemistry in clinical samples from a retrospective cohort of 72 patients with primary TSCC who were treated at our institution from Jan. 2007 to Dec. 2013. The potential associations between SUZ12 abundance and multiple clinicopathological parameters were assessed by Chi square test. Moreover, the effect of SUZ12 expression on patients’ survival was further estimated by Kaplan–Meier and Cox regression analyses. RESULTS: Our immunohistochemical staining data revealed aberrant overexpression of SUZ12 in a large subset of TSCC as compared to normal tongue mucosa. Elevated SUZ12 was found to be significantly associated with cervical nodes metastasis (P = 0.0325) and reduced overall as well as disease-free survival (Log-rank test, P = 0.0225, 0.0179, respectively). Both univariate and multivariate Cox regression analysis identified the expression status of SUZ12 (low/high) as an important independent prognostic factor for patients’ survival. CONCLUSIONS: Our data reveal that aberrant SUZ12 overexpression is associated with cervical nodes metastasis and reduced survival in TSCC. These findings suggest that SUZ12 might play critical roles during tongue tumorigenesis and serve as a novel biomarker with diagnostic and prognostic significance

Can neoadjuvant chemoradiotherapy combined with immunotherapy benefit patients with microsatellite stable locally advanced rectal cancer? a pooled and integration analysis

ObjectiveTo assess the clinical efficacy of neoadjuvant chemoradiotherapy combined with immunotherapy for patients with microsatellite stable (MSS) locally advanced rectal cancer and provide evidence to support clinical decision-making.MethodsA systematic search was conducted on the PubMed, Embase, Cochrane Collaboration databases, conference summaries, and Chinese databases for clinical studies that investigated neoadjuvant chemoradiotherapy combined with immunotherapy for the treatment of locally advanced rectal cancer with MSS status. The search spanned from the inception of each database through July 2023. Data from the identified studies were extracted using a pre-designed table, and efficacy outcomes were analyzed. An integrated analysis was conducted using Stata 12.0 software.ResultsEight studies were included, comprising 204 patients with locally advanced MSS rectal cancer who received chemoradiotherapy combined with immunotherapy. The integrated analysis revealed a pathologic complete remission rate of 0.33, a sphincter preservation rate of 0.86, an R0 resection rate of 0.83, a major pathologic remission rate of 0.33, and a clinical complete remission rate of 0.30.ConclusionNeoadjuvant chemoradiotherapy combined with immunotherapy demonstrates significant short-term efficacy in MSS-type locally advanced rectal cancer, notably enhancing the pathologic complete remission and sphincter preservation rates. This combination is a recommended treatment for patients with MSS-type rectal cancer

Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death

Mitochondrial calcium uniporter (MCU) is a conserved Ca(2+) transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress-induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca(2+) uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca(2+) uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases

Differential Impacts of Soybean and Fish Oils on Hepatocyte Lipid Droplet Accumulation and Endoplasmic Reticulum Stress in Primary Rabbit Hepatocytes

Parenteral nutrition-associated liver disease (PNALD) is a severe ailment associated with long-term parenteral nutrition. Soybean oil-based lipid emulsions (SOLE) are thought to promote PNALD development, whereas fish oil-based lipid emulsions (FOLE) are thought to protect against PNALD. This study aimed to investigate the effects of SOLE and FOLE on primary rabbit hepatocytes. The results reveal that SOLE caused significant endoplasmic reticulum (ER) and mitochondrial damage, ultimately resulting in lipid droplets accumulation and ER stress. While these deleterious events induce hepatocyte injury, FOLE at high doses cause only minor ER and mitochondrial damage, which has no effect on hepatic function. SOLE also significantly upregulated glucose-regulated protein 94 mRNA and protein expression. These data indicate that SOLE, but not FOLE, damage the ER and mitochondria, resulting in lipid droplets accumulation and ER stress and, finally, hepatocyte injury. This likely contributes to the differential impacts of SOLE and FOLE on PNALD development and progression

Observation of whistler wave instability driven by temperature anisotropy of energetic electrons on EXL-50 spherical torus

Electromagnetic modes in the frequency range of 30-120MHz were observed in electron cyclotron wave (ECW) steady state plasmas on the ENN XuanLong-50 (EXL-50) spherical torus. These modes were found to have multiple bands of frequencies proportional to the Alfv\'en velocity. This indicates that the observed mode frequencies satisfy the dispersion relation of whistler waves. In addition, suppression of the whistler waves by the synergistic effect of Lower Hybrid Wave (LHW) and ECW was also observed. This suggests that the whistler waves were driven by temperature anisotropy of energetic electrons. These are the first such observations (not runaway discharge) made in magnetically confined toroidal plasmas and may have important implications for studying wave-particle interactions, RF wave current driver, and runaway electron control in future fusion devices

The 2023 wearable photoplethysmography roadmap

Photoplethysmography is a key sensing technology which is used in wearable devices such as smartwatches and fitness trackers. Currently, photoplethysmography sensors are used to monitor physiological parameters including heart rate and heart rhythm, and to track activities like sleep and exercise. Yet, wearable photoplethysmography has potential to provide much more information on health and wellbeing, which could inform clinical decision making. This Roadmap outlines directions for research and development to realise the full potential of wearable photoplethysmography. Experts discuss key topics within the areas of sensor design, signal processing, clinical applications, and research directions. Their perspectives provide valuable guidance to researchers developing wearable photoplethysmography technology

Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics

Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification