Comparative Insight into Microglia/Macrophages-Associated Pathways in Glioblastoma and Alzheimer's Disease.

Microglia and macrophages are pivotal to the brain's innate immune response and have garnered considerable attention in the context of glioblastoma (GBM) and Alzheimer's disease (AD) research. This review delineates the complex roles of these cells within the neuropathological landscape, focusing on a range of signaling pathways-namely, NF-κB, microRNAs (miRNAs), and TREM2-that regulate the behavior of tumor-associated macrophages (TAMs) in GBM and disease-associated microglia (DAMs) in AD. These pathways are critical to the processes of neuroinflammation, angiogenesis, and apoptosis, which are hallmarks of GBM and AD. We concentrate on the multifaceted regulation of TAMs by NF-κB signaling in GBM, the influence of TREM2 on DAMs' responses to amyloid-beta deposition, and the modulation of both TAMs and DAMs by GBM- and AD-related miRNAs. Incorporating recent advancements in molecular biology, immunology, and AI techniques, through a detailed exploration of these molecular mechanisms, we aim to shed light on their distinct and overlapping regulatory functions in GBM and AD. The review culminates with a discussion on how insights into NF-κB, miRNAs, and TREM2 signaling may inform novel therapeutic approaches targeting microglia and macrophages in these neurodegenerative and neoplastic conditions. This comparative analysis underscores the potential for new, targeted treatments, offering a roadmap for future research aimed at mitigating the progression of these complex diseases.

A Novel Noncoding RNA dsr11 Involved in Heat Stress Tolerance in Deinococcus radiodurans.

Deinococcus radiodurans is an extremely resistant bacteria that has evolved masterful strategies to enable survival under various environmental stress conditions. Heat stress is a major environmental stress factor that can cause denaturation of proteins, membrane disruption, and oxidative stress. Previous studies have examined the mechanisms of the heat stress response by analyzing changes in protein levels; however, little is known about the role of small noncoding RNAs (ncRNAs), which are known to play important regulatory functions in bacteria during various environmental stress response. The ncRNA dsr11 of D. radiodurans was previously identified by RNA-seq and Northern blot. In this study, we showed that the transcription level of dsr11 was up-regulated 4.2-fold under heat stress by qRT-PCR analysis. Heat tolerance assay showed that deleting dsr11 significantly inhibited the viability under high temperature conditions. To assess the influence of dsr11 on the D. radiodurans transcriptome, 157 genes were found differentially expressed in the knock-out mutant by RNA-seq experiment. Combining RNA-seq and in silico analysis, we found that trmE (tRNA modification GTPase) and dr_0651 (arginase) were likely to be the direct targets of dsr11. Further microscale thermophoresis results demonstrated that dsr11 can directly bind to the mRNA of trmE and dr_0651. Our results indicated that dsr11 can enhance the tolerance to heat stress of D. radiodurans by binding to trmE and dr_0651 mRNA. Overall, these results extend our understanding of ncRNA regulation and provide new insights into the heat stress response in D. radiodurans.

Occurrence of Salmonella genomic island 1 (SGI1) in two African Proteus mirabilis strains isolated from diseased chicken flocks.

Two P. mirabilis strains, PmSHR21 and PmSHR38, were collected from chicken flocks in Sharkia Governorate, Egypt in 2016. The two strains showed multidrug-resistance (MDR) phenotypes and were detected to harbour I) floR and sul1 genes conferring resistance to florfenicol and chloramphenicol, and sulfonamides, respectively, II) a ~1.9 kbp class 1 integron containing aadA2-lnuF genes conferring resistance to spectinomycin and streptomycin, and lincosamides, respectively. Interestingly, the two strains were detected to contain SGI1 variant, SGI1-W and inserted between the 3' end of the chromosomal trmE gene and the hipB/hipA toxin/antitoxin homologue. Fingerprinting by ERIC-PCR of the two poultry strains identified in this study and the two human SGI1-carrying P. mirabilis strains described recently in our study showed identical ERIC-pattern between SGI1-W-carrying poultry and human strains, suggesting that they might be clonally related. The detection of SGI1 and its variants in P. mirabilis isolated from humans and chicken flocks in Egypt clarify the geographical and biological spreading through an inter-transmission pathway. To the best of our knowledge, this is the first study detecting SGI1-positive P. mirabilis isolated from chicken flocks in Africa.

Exploring potassium-dependent GTP hydrolysis in TEES family GTPases.

GTPases are important regulatory proteins that hydrolyze GTP to GDP. A novel GTP-hydrolysis mechanism is employed by MnmE, YqeH and FeoB, where a potassium ion plays a role analogous to the Arginine finger of the Ras-RasGAP system, to accelerate otherwise slow GTP hydrolysis rates. In these proteins, two conserved asparagines and a 'K-loop' present in switch-I, were suggested as attributes of GTPases employing a K(+)-mediated mechanism. Based on their conservation, a similar mechanism was suggested for TEES family GTPases. Recently, in Dynamin, Fzo1 and RbgA, which also conserve these attributes, a similar mechanism was shown to be operative. Here, we probe K(+)-activated GTP hydrolysis in TEES (TrmE-Era-EngA-YihA-Septin) GTPases - Era, EngB and the two contiguous G-domains, GD1 and GD2 of YphC (EngA homologue) - and also in HflX, another GTPase that also conserves the same attributes. While GD1-YphC and Era exhibit a K(+)-mediated activation of GTP hydrolysis, surprisingly GD2-YphC, EngB and HflX do not. Therefore, the attributes identified thus far, do not necessarily predict a K(+)-mechanism in GTPases and hence warrant extensive structural investigations.