Central-venous-catheter-related bloodstream infections (CRBSIs) are an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. Consequences depend on associated organisms, underlying pre-morbid conditions, timeliness, and appropriateness of the treatment/interventions received. We have summarized risk factors, pathogenesis, etiology, diagnosis, and management of CRBSI in this review.

Mitochondrial mRNAs in kinetoplastids require extensive U-insertion/deletion editing that progresses 3 ′ -to-5 ′ in small blocks, each directed by a guide RNA (gRNA), and exhibits substrate and developmental stage-specificity by unsolved mechanisms. Here, we address compositionally related factors, collectively known as the mitochondrial RNA-binding complex 1 (MRB1) or gRNAbinding complex (GRBC), that contain gRNA, have a dynamic protein composition, and transiently associate with several mitochondrial factors including RNA editing core complexes (RECC) and ribosomes. MRB1 controls editing by still unknown mechanisms. We performed the first next-generation sequencing study of native subcomplexes of MRB1, immunoselected via either RNA helicase 2 (REH2), that binds RNA and associates with unwinding activity, or MRB3010, that affects an early editing step. The particles contain either REH2 or MRB3010 but share the core GAP1 and other proteins detected by RNA photo-crosslinking. Analyses of the first editing blocks indicate an enrichment of several initiating gRNAs in the MRB3010-purified complex. Our data also indicate fast evolution of mRNA 3 ′ ends and strain-specific alternative 3 ′ editing within 3 ′ UTR or C-terminal protein-coding sequence that could impact mitochondrial physiology. Moreover, we found robust specific copurification of edited and pre-edited mRNAs, suggesting that these particles may bind both mRNA and gRNA editing substrates. We propose that multiple subcomplexes of MRB1 with different RNA/protein composition serve as a scaffold for specific assembly of editing substrates and RECC, thereby forming the editing holoenzyme. The MRB3010-subcomplex may promote early editing through its preferential recruitment of initiating gRNAs.

Adaptation and survival of Trypanosoma brucei requires editing of mitochondrial mRNA by uridylate (U) insertion and deletion. Hundreds of small guide RNAs (gRNAs) direct the mRNA editing at over 3,000 sites. RNA editing is controlled during the life cycle but the regulation of substrate and stage specificity remains unknown. Editing progresses in the 3’ to 5’ direction along the pre-mRNA in blocks, each targeted by a unique gRNA. A critical editing factor is the mitochondrial RNA binding complex 1 (MRB1) that binds gRNA and transiently interacts with the catalytic RNA editing core complex (RECC). MRB1 is a large and dynamic complex that appears to be comprised of distinct but related subcomplexes (termed here MRBs). MRBs seem to share a ‘core’ complex of proteins but differ in the composition of the ‘variable’ proteins. Since some proteins associate transiently the MRBs remain imprecisely defined. MRB1 controls editing by unknown mechanisms, and the functional relevance of the different MRBs is unclear. We previously identified two distinct MRBs, and showed that they carry mRNAs that undergo editing. We proposed that editing takes place in the MRBs because MRBs stably associate with mRNA and gRNA but only transiently interact with RECC, which is RNA free. Here, we identify the first specialized functions in MRBs: 1) 3010-MRB is a major scaffold for RNA editing, and 2) REH2-MRB contains a critical trans-acting RNA helicase (REH2) that affects multiple steps of editing function in 3010-MRB. These trans effects of the REH2 include loading of unedited mRNA and editing in the first block and in subsequent blocks as editing progresses. REH2 binds its own MRB via RNA, and conserved domains in REH2 were critical for REH2 to associate with the RNA and protein components of its MRB. Importantly, REH2 associates with a ~30 kDa RNA-binding protein in a novel ~15S subcomplex in RNA-depleted mitochondria. We use these new results to update our model of MRB function and organization.

Mitochondrial mRNAs in Trypanosoma brucei undergo extensive insertion and deletion of uridylates that are catalyzed by the RNA editing core complex (RECC) and directed by hundreds of small guide RNAs (gRNAs) that base pair with mRNA. RECC is largely RNA-free, and accessory mitochondrial RNAbinding complex 1 (MRB1) variants serve as scaffolds for the assembly of mRNA-gRNA hybrids and RECC. However, the molecular steps that create higher-order holoenzymes ("editosomes") are unknown. Previously, we identified an RNA editing helicase 2-associated subcomplex (REH2C) and showed that REH2 binds RNA. Here we showed that REH2C is an mRNA-associated ribonucleoprotein (mRNP) subcomplex with editing substrates, intermediates, and products. We isolated this mRNP from mitochondria lacking gRNA-bound RNP (gRNP) subcomplexes and identified REH2-associated cofactors 1 and 2 ( H2 F1 and H2 F2). H2 F1 is an octa-zinc finger protein required for mRNP-gRNP docking, pre-mRNA and RECC loading, and RNP formation with a short synthetic RNA duplex. REH2 and other eukaryotic DEAH/RHA-type helicases share a conserved regulatory C-terminal domain cluster that includes an oligonucleotide-binding fold. Recombinant REH2 and H2 F1 constructs associate in a purified complex in vitro. We propose a model of stepwise editosome assembly that entails controlled docking of mRNP and gRNP modules via specific base pairing between their respective mRNA and gRNA cargo and regulatory REH2 and H2 F1 subunits of the novel mRNP that may control specificity checkpoints in the editing pathway.RNA editing by uridylate insertion and deletion in Trypanosoma brucei modifies over 3000 sites in mitochondrial mRNAs in a gradual process directed by hundreds of small guide RNAs (gRNAs) 4 (1-3). The basic regulatory mechanisms of substrate specificity and developmental control in RNA editing remain unknown. The uridylate changes are catalyzed by the RECC enzyme from 3Ј to 5Ј in discrete blocks. Each gRNA directs editing of one mRNA block. Surprisingly, RECC has little or no RNA and lacks the processivity found in vivo, as established in early purifications of this multiprotein enzyme (4 -6). So, accessory components of the editing apparatus must facilitate substrate recruitment and editing catalysis. There are many non-RECC proteins that affect editing. Most of these proteins (Ͼ25 proteins) are components of the MRB1 complex in T. brucei, also termed gRNA-binding complex (GRBC) in Leishmania, that binds and stabilizes gRNA. MRB1 interacts transiently with the RECC enzyme and mitoribosomes (1,7,8). It has also been found that MRB1 contains all three classes of mRNA in editing: unedited pre-mRNAs, partially edited intermediates, and fully edited transcripts. This indicates that MRB1 complexes serve as scaffolds for the assembly of hybrid substrates and the RECC enzyme (9 -11). Transient addition of RECC to these scaffolds would establish higher-order editing holoenzymes or editosomes. MRB1 was first considered a single dynamic complex, but the reason of its variable compos...

We believe better understanding of the anatomical relationships of the tarsal tunnel and a clear communication system among anatomists, neuroradiologists and foot and ankle surgeons will facilitate accurate preoperative localization of the site of nerve compression possibly leading to better outcomes.

Food preservatives play important role in today's food supplies that are used to prolong the self-life of products by protecting them from deterioration caused by micro-organisms. In this study, investigations were carried out to study the impacts of food preservatives like butylated hydroxytoluene, butylated hydroxyanisole, sorbic acid, propyl gallate and sodium nitrate. The effects of these preservatives at concentration of 1000 ppm, 1500 ppm, 2000 ppm, 2500 ppm for 4 h, 8 h and 16 h of exposure period were studied on the root tips of Allium cepa. Cytological studies revealed statistically significant (p < 0.05) inhibition in mitotic index with an increase in concentration of the food preservatives when compared with the control. Most frequent cytological abnormalities observed were bridges, multipolarity, C-mitosis, stickiness and cell death. The total percentages of abnormalities were also increased with increasing concentration and time duration. The abnormalities (%) in root system caused by used preservatives were recorded as butylated hydroxytoluene < butylated hydroxyanisole < sodium nitrate < sorbic acid < propyl gallate.

Cutaneous fungal infections are a widespread public health concern affecting millions of people all across the world. Nearly half of those affected will experience multiple episodes of infection requiring numerous rounds of treatment. Tinea pedis is a common superficial fungal skin infection of the feet. It is emerging as an important and a significantly prevalent infection in an increasingly aging population and immunocompromised patients. This mycotic infection is contagious, frequently misdiagnosed and often inadequately treated. Considering the uprising prevalence of tinea pedis, in this review article predisposing factors, etiologic agents involved in pathogenesis, clinical presentation of the disease, proper diagnostic tests and the treatment options commercially available are reviewed.

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