RDR6-mediated synthesis of complementary RNA is terminated by miRNA stably bound to template RNA

RNA-dependent RNA polymerase RDR6 is involved in the biogenesis of plant trans-acting siRNAs. This process is initiated by miRNA-directed and Argonaute (AGO) protein-mediated cleavage of TAS gene transcripts. One of the cleavage products is converted by RDR6 to double-stranded (ds)RNA, the substrate for Dicer-like 4 (DCL4). Interestingly, TAS3 transcript contains two target sites for miR390::AGO7 complexes, 5′-non-cleavable and 3′-cleavable. Here we show that RDR6-mediated synthesis of complementary RNA starts at a third nucleotide of the cleaved TAS3 transcript and is terminated by the miR390::AGO7 complex stably bound to the non-cleavable site. Thus, the resulting dsRNA has a short, 2-nt, 3′-overhang and a long, 220-nt, 5′-overhang of the template strand. The short, but not long, overhang is optimal for DCL4 binding, which ensures dsRNA processing from one end into phased siRNA duplexes with 2-nt 3′-overhang

RDR6-mediated synthesis of complementary RNA is terminated by miRNA stably bound to template RNA

RNA-dependent RNA polymerase RDR6 is involved in the biogenesis of plant trans-acting siRNAs. This process is initiated by miRNA-directed and Argonaute (AGO) protein-mediated cleavage of TAS gene transcripts. One of the cleavage products is converted by RDR6 to double-stranded (ds)RNA, the substrate for Dicer-like 4 (DCL4). Interestingly, TAS3 transcript contains two target sites for miR390::AGO7 complexes, 5′-non-cleavable and 3′-cleavable. Here we show that RDR6-mediated synthesis of complementary RNA starts at a third nucleotide of the cleaved TAS3 transcript and is terminated by the miR390::AGO7 complex stably bound to the non-cleavable site. Thus, the resulting dsRNA has a short, 2-nt, 3′-overhang and a long, 220-nt, 5′-overhang of the template strand. The short, but not long, overhang is optimal for DCL4 binding, which ensures dsRNA processing from one end into phased siRNA duplexes with 2-nt 3′-overhangs

Continuing Education During Times of War: Experiences of Children in Northern Sri Lanka

The primary objective of the study was to explore the experiences of children during and after 30 years of civil war with particular attention on its impact on their academic learning. The research intended to answer two research questions, namely 1) How did the war impact on children’s education? and 2) What support networks were available for children affected by war to remain in school and/or to continuously engage in academic learning? The research was carried out in the Jaffna District of Northern Sri Lanka and depended entirely on qualitative data generated through in-depth interviews, key informant interviews, focus groups discussions and observations. Multiple displacements caused by war, the impact of war on livelihoods and the trauma caused by war has resulted in some students losing interest in school and eventually dropping out. In spite of various financial and other support provided by local and international NGOs only some children have remained in school with a sustained interest in education. A characteristic common to these children was that they came from more ‘secure’ family backgrounds. The security offered by intimate relationships within the family seems crucial for educational success even during times of war. The findings suggest the need for strengthening family well-being and stronger emotional support to ensure sustained interest in education during times of war

Protective effect of CV247 against cisplatin nephrotoxicity in rats

CV247 (CV), an aqueous mixture of copper (Cu) and manganese (Mn) gluconates, vitamin C and sodium salicylate increased the antitumour effects of cisplatin (CDPP; cis-diamminedichloroplatinum) in vitro. We hypothesized that the antioxidant and cyclooxygenase-2 (COX-2; prostaglandin-endoperoxide synthase 2) inhibitory components of CV can protect the kidneys from CDPP nephrotoxicity in rats. CDPP (6.5 mg/kg, intraperitoneally) slightly elevated serum creatinine (Crea) and blood urea nitrogen (BUN) 12 days after treatment. Kidney histology demonstrated extensive tubular epithelial damage and COX-2 immunoreactivity increased 14 days after treatment. A large amount of platinum (Pt) accumulated in the kidney of CDPP-treated rats. Furthermore, CDPP decreased renal iron (Fe), molybdenum (Mo), zinc (Zn), Cu and Mn concentrations and increased plasma Fe and Cu concentrations. CDPP elevated plasma free radical concentration. Treatment with CV alone for 14 days (twice 3 ml/kg/day orally) did not influence these parameters. Chronic CV administration after CDPP reduced renal histological damage and slightly decreased COX-2 immunoreactivity, while failed to prevent the increase in Crea and BUN levels. Blood free radical concentration was reduced, that is, CV improved redox homeostasis. CV restored plasma Fe and renal Fe, Mo and Zn, while decreased Pt and elevated Cu and Mn concentrations in the kidney. Besides the known synergistic antitumour effects with CDPP, CV partially protected the kidneys from CDPP nephrotoxicity probably through its antioxidant effect

Perceived barriers to management of chronic kidney disease

INTRODUCTION: The number of patients with chronic kidney disease (CKD) is gradually increasing in developing countries such as Rwanda. Barriers to the management of CKD from nurses' perspectives is not an area that has been well explored. This study aimed to assess the perceived barriers to CKD management from the perspective of nurses working at the referral hospitals in Rwanda.METHODS: The study used a cross-sectional research design. The study setting was selected referral hospitals in Kigali. A convenience sample of 55 nurses was obtained and data was collected using a self-administered questionnaire. Analyses were done using descriptive and inferential statistics in the SPSS application.RESULTS: Respondents identified the most barriers to management of CKD as: limited knowledge of CKD (96%) and its risk factor of glomerulonephritis (93%), limited information of dialysis (98%) and fluid restriction (95%) treatment as well as a lack of further training on nephrology nursing (93%). Shortage of nephrologists and nurses (98%) and a multidisciplinary care team (95%) were resource barriers. Other barriers were limited knowledge of CKD risk factors: hypertension (78%) and HIV/AIDS (80%), limited in-service training (69%), and non-adherence (86%). The experience of respondents was associated with limited knowledge of CKD risk factors: hypertension (P =0.001), diabetes (P=0.001) and HIV/AIDS (P=0.040). The level of nursing obtained by the respondents was associated with a lack of further special training (p=0. 001), limited in-service training (P=0.028) and non-adherence of CKD patients (P=0.017).CONCLUSION: Barriers to CKD management in Rwanda are evident. There is a need for in-service training for nurses in order to improve the proper treatment of the CKD population.&nbsp

Sequencing of RDR6-dependent double-stranded RNAs reveals novel features of plant siRNA biogenesis

Biogenesis of trans-acting siRNAs (tasiRNAs) is initiated by miRNA-directed cleavage of TAS gene transcripts and requires RNA-dependent RNA polymerase 6 (RDR6) and Dicer-like 4 (DCL4). Here, we show that following miR173 cleavage the entire polyadenylated parts of Arabidopsis TAS1a/b/c and TAS2 transcripts are converted by RDR6 to double-stranded (ds)RNAs. Additionally, shorter dsRNAs are produced following a second cleavage directed by a TAS1c-derived siRNA. This tasiRNA and miR173 guide Argonaute 1 complexes to excise the segments from TAS2 and three TAS1 transcripts including TAS1c itself to be converted to dsRNAs, which restricts siRNA production to a region between the two cleavage sites. TAS1c is also feedback regulated by a cis-acting siRNA. We conclude that TAS1c generates a master siRNA that controls a complex network of TAS1/TAS2 siRNA biogenesis and gene regulation. TAS1/TAS2 short dsRNAs produced in this network are processed by DCL4 from both ends in distinct registers, which increases repertoires of tasiRNA

4-(4-Bromo­phen­yl)-6-(1H-indol-3-yl)-2,2′-bipyridine-5-carbonitrile

In the title compound, C25H15BrN4, the two pyridine rings lie in a common plane [r.m.s. deviation = 0.023 (2) Å], whereas the bromo­phenyl and indole rings are twisted away from this plane by 52.82 (12) and 28.02 (10)°, respectively. The crystal structure is stabilized by inter­molecular N—H⋯N inter­actions

Trimethyl 1-(2-methyl-1-phenylsulfonyl-1H-indol-3-yl)propane-1,2,3-tricarbox­ylate

In the title compound, C24H25NO8S, the indole unit is planar and makes a dihedral angle of 79.73 (11)° with the phenyl ring of the sulfonyl substituent. The mol­ecules in the unit cell are stabilized by C—H⋯O and C—H⋯π inter­molecular inter­actions in addition to van der Waals forces

8-Hydroxy-2-methylquinoline

The asymmetric unit of the title compound, C10H9NO, contains two independent mol­ecules which are linked by a pair of O—H⋯N hydrogen bonds into a hydrogen-bonded dimer