Pain is a major health problem, affecting over fifty million adults in the US alone, with significant economic cost in medical care and lost productivity. Despite evidence implicating nicotinic acetylcholine receptors (nAChRs) in pathological pain, their specific contribution to pain processing in the spinal cord remains unclear given their presence in both neuronal and non-neuronal cell types. Here we investigated if loss of neuronal-specific TMEM35a (NACHO), a novel chaperone for functional expression of the homomeric α7 and assembly of the heteromeric α3, α4, and α6-containing nAChRs, modulates pain in mice.  https://www.selleckchem.com/products/pixantrone-maleate.html  Mice with tmem35a deletion exhibited thermal hyperalgesia and mechanical allodynia. Intrathecal administration of nicotine and the α7-specific agonist, PHA543613, produced analgesic responses to noxious heat and mechanical stimuli in tmem35a KO mice, respectively, suggesting residual expression of these receptors or off-target effects. Since NACHO is expressed only in neurons, these findings indicate that neuronal α7 nAChR in the spinal cord contributes to heat nociception. To further determine the molecular basis underlying the pain phenotype, we analyzed the spinal cord transcriptome. Compared to WT control, the spinal cord of tmem35a KO mice exhibited 72 differentially-expressed genes (DEGs). These DEGs were mapped onto functional gene networks using the knowledge-based database, Ingenuity Pathway Analysis, and suggests increased neuroinflammation as a potential contributing factor for the hyperalgesia in tmem35a KO mice. Collectively, these findings implicate a heightened inflammatory response in the absence of neuronal NACHO activity. Additional studies are needed to determine the precise mechanism by which NACHO in the spinal cord modulates pain.CDGSH Iron Sulfur Domain 2 (CISD2) is the causative gene for the disease Wolfram syndrome 2 (WFS2; MIM 604928), which is an autosomal recessive disorder showing metabolic and neurodegenerative manifestations. CISD2 protein can be localized on the endoplasmic reticulum (ER), outer mitochondrial membrane (OMM) and mitochondria-associated membrane (MAM). CISD2 plays a crucial role in the regulation of cytosolic Ca2+ homeostasis, ER integrity and mitochondrial function. Here we summarize the most updated publications and discuss the central role of CISD2 in maintaining cellular homeostasis. This review mainly focuses on the following topics. Firstly, that CISD2 has been recognized as a prolongevity gene and the level of CISD2 is a key determinant of lifespan and healthspan. In mice, Cisd2 deficiency shortens lifespan and accelerates aging. Conversely, a persistently high level of Cisd2 promotes longevity. Intriguingly, exercise stimulates Cisd2 gene expression and thus, the beneficial effects offered by exercise may be partly related to Cisd2 activation. Secondly, that Cisd2 is down-regulated in a variety of tissues and organs during natural aging. Three potential mechanisms that may mediate the age-dependent decrease of Cisd2, via regulating at different levels of gene expression, are discussed. Thirdly, the relationship between CISD2 and cell survival, as well as the potential mechanisms underlying the cell death control, are discussed. Finally we discuss that, in cancers, CISD2 may functions as a double-edged sword, either suppressing or promoting cancer development. This review highlights the importance of the CISD2 in aging and age-related diseases and identifies the urgent need for the translation of available genetic evidence into pharmaceutic interventions in order to alleviate age-related disorders and extend a healthy lifespan in humans.Triple negative breast cancer (TNBC) has poor prognosis due to lack of biomarker and therapeutic target. Emerging research has revealed long noncoding RNAs (lncRNAs) are involved in breast cancer progression, but their functions and regulatory mechanisms remain poorly understood, especially in TNBC. In this study, we performed lncRNA microarray analysis of five TNBC samples and their matched normal tissues, and discovered a number of differentially expressed lncRNAs. We identified an antisense lncRNA, HYOU1-AS, which is transcribed from the opposite strand of the hypoxia up-regulated 1 (HYOU1) gene, enriched in the nucleus and highly expressed in TNBC. HYOU1-AS knockdown could inhibit the proliferation and migration of the TNBC MDA-MB-231 cells, and reduce their xenograft tumor formation in nude mice. In mechanistic studies, we found that HYOU1-AS could promote the expression of HYOU1, a proliferative gene, through competitively binding to hnRNPA1, an RNA-binding protein, to relieve its post-transcriptional inhibition of the HYOU1 mRNA. Consistently, increased HYOU1 levels correlated with poor clinical outcomes of breast cancer patients based on our study of the TCGA database. Overall, our data indicated that the lncRNA HYOU1-AS promoted TNBC progression through upregulating HYOU1.We have studied the interaction of a VegT mRNA localization signal sequence with the membranes of the mitochondrial cloud in Xenopus oocytes, and the binding of the VegT mRNA signal sequence to the lipid raft regions of the vesicles bounded by ordered and disordered phospholipid bilayers. RNA preference for the membranes of the mitochondrial cloud was confirmed using microscopy of a fluorescence resonance energy transfer from RNA molecules to membranes. Our studies show that VegT mRNA has a higher affinity for ordered regions of lipid bilayers. This conclusion is supported by the dissociation constant measurements for RNA-liposome complex and the visualization of the FRET signal between giant vesicles and RNA. Our data indicate that these affinities are sensitive and distinct to the location of the localization elements within the VegT mRNA localization signal structure. Therefore, specific binding of VegT mRNA localization signal sequence to membranes can be responsible for polarized distribution of VegT mRNA in Xenopus oocytes. We suggest that the mechanism of this binding can involve the interaction of the localization elements within the VegT mRNA signal sequence with lipid raft regions of the mitochondrial cloud membranes, thereby utilizing localization elements as novel lipid raft-binding RNA motifs.