Global Regulatory Functions of the Staphylococcus aureus Endoribonuclease III in Gene Expression

RNA turnover plays an important role in both virulence and adaptation to stress in the Gram-positive human pathogen Staphylococcus aureus. However, the molecular players and mechanisms involved in these processes are poorly understood. Here, we explored the functions of S. aureus endoribonuclease III (RNase III), a member of the ubiquitous family of double-strand-specific endoribonucleases. To define genomic transcripts that are bound and processed by RNase III, we performed deep sequencing on cDNA libraries generated from RNAs that were co-immunoprecipitated with wild-type RNase III or two different cleavage-defective mutant variants in vivo. Several newly identified RNase III targets were validated by independent experimental methods. We identified various classes of structured RNAs as RNase III substrates and demonstrated that this enzyme is involved in the maturation of rRNAs and tRNAs, regulates the turnover of mRNAs and non-coding RNAs, and autoregulates its synthesis by cleaving within the coding region of its own mRNA. Moreover, we identified a positive effect of RNase III on protein synthesis based on novel mechanisms. RNase III–mediated cleavage in the 5′ untranslated region (5′UTR) enhanced the stability and translation of cspA mRNA, which encodes the major cold-shock protein. Furthermore, RNase III cleaved overlapping 5′UTRs of divergently transcribed genes to generate leaderless mRNAs, which constitutes a novel way to co-regulate neighboring genes. In agreement with recent findings, low abundance antisense RNAs covering 44% of the annotated genes were captured by co-immunoprecipitation with RNase III mutant proteins. Thus, in addition to gene regulation, RNase III is associated with RNA quality control of pervasive transcription. Overall, this study illustrates the complexity of post-transcriptional regulation mediated by RNase III

Randomized clinical trial of surgery versus conservative therapy for carpal tunnel syndrome [ISRCTN84286481]

BACKGROUND: Conservative treatment remains the standard of care for treating mild to moderate carpal tunnel syndrome despite a small number of well-controlled studies and limited objective evidence to support current treatment options. There is an increasing interest in the usefulness of wrist magnetic resonance imaging could play in predicting who will benefit for various treatments. METHOD AND DESIGN: Two hundred patients with mild to moderate symptoms will be recruited over 3 1/2 years from neurological surgery, primary care, electrodiagnostic clinics. We will exclude patients with clinical or electrodiagnostic evidence of denervation or thenar muscle atrophy. We will randomly assign patients to either a well-defined conservative care protocol or surgery. The conservative care treatment will include visits with a hand therapist, exercises, a self-care booklet, work modification/ activity restriction, B6 therapy, ultrasound and possible steroid injections. The surgical care would be left up to the surgeon (endoscopic vs. open) with usual and customary follow-up. All patients will receive a wrist MRI at baseline. Patients will be contacted at 3, 6, 9 and 12 months after randomization to complete the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ). In addition, we will compare disability (activity and work days lost) and general well being as measured by the SF-36 version II. We will control for demographics and use psychological measures (SCL-90 somatization and depression scales) as well as EDS and MRI predictors of outcomes. DISCUSSION: We have designed a randomized controlled trial which will assess the effectiveness of surgery for patients with mild to moderate carpal tunnel syndrome. An important secondary goal is to study the ability of MRI to predict patient outcomes

Central centrifugal cicatricial alopecia: challenges and solutions

Ingrid Herskovitz, Mariya Miteva Department of Dermatology and Cutaneous Surgery, University of Miami L Miller School of Medicine, Miami, FL, USA Abstract: Central centrifugal cicatricial alopecia (CCCA) is the most common scarring alopecia among African American women. Data about epidemiology, etiology, genetic inheritance, and management are scarce and come from individual reports or small series. CCCA has been associated with hot combing and traumatic hair styling for years; however, studies fail to confirm it as the sole etiologic factor. It has been shown in a small series that CCCA can be inherited in an autosomal dominant fashion, with a partial penetrance and a strong modifying effect of hairstyling and sex. CCCA presents clinically as a central area of progressive irreversible hair loss that expands to the periphery. A patchy form has also been described. Dermoscopy is helpful to identify the optimal site for the biopsy, which establishes the diagnosis. Well-designed randomized controlled trials are needed to discover the optimal management. At this point, patients are advised to avoid traction and chemical treatments; topical and intralesional steroids, calcineurin inhibitors, and minoxidil can be helpful in halting the progression. Keywords: hair loss, alopecia, dermatoscopy, dermoscopy, trichoscopy, black scalp, African American, scarring alopeci

Central centrifugal cicatricial alopecia: challenges and solutions

Ingrid Herskovitz, Mariya Miteva Department of Dermatology and Cutaneous Surgery, University of Miami L Miller School of Medicine, Miami, FL, USA Abstract: Central centrifugal cicatricial alopecia (CCCA) is the most common scarring alopecia among African American women. Data about epidemiology, etiology, genetic inheritance, and management are scarce and come from individual reports or small series. CCCA has been associated with hot combing and traumatic hair styling for years; however, studies fail to confirm it as the sole etiologic factor. It has been shown in a small series that CCCA can be inherited in an autosomal dominant fashion, with a partial penetrance and a strong modifying effect of hairstyling and sex. CCCA presents clinically as a central area of progressive irreversible hair loss that expands to the periphery. A patchy form has also been described. Dermoscopy is helpful to identify the optimal site for the biopsy, which establishes the diagnosis. Well-designed randomized controlled trials are needed to discover the optimal management. At this point, patients are advised to avoid traction and chemical treatments; topical and intralesional steroids, calcineurin inhibitors, and minoxidil can be helpful in halting the progression. Keywords: hair loss, alopecia, dermatoscopy, dermoscopy, trichoscopy, black scalp, African American, scarring alopeci