New insights into the novel and functional promoter sequences of b-1,3-glucanase gene from Hevea brasiliensis

β-1,3-glucanases play a major role in combating the abnormal leaf fall disease (ALF) caused by the oomycete Phytophthora spp. in Hevea brasiliensis, the major commercial source of natural rubber. In this study, partial sequences of four novel promoters of differentβ-1,3-glucanase genomic forms were amplified through inverse PCR from the H. brasiliensis clone RRII 105 and sequence characterized. This is the first report showingβ-1,3-glucanase genes driven by a different set of promoter sequences in a single clone of Hevea. The nucleotide sequencing revealed the presence of 913, 582, 553 and 198 bp promoter regions upstream to the translation initiation codon, ‘ATG’, and contained the essential cis-elements that are usually present in biotic/abiotic stress-related plant gene promoters along with other complex regulatory regions. The amplified regions showed strong nucleosome formation potential and in two of the promoters CpG islands were observed indicating the tight regulation of gene expression by the promoters. The functional efficiency of the isolated promoter forms was validated using promoter: reporter gene (GUS) fusion binary vectors through Agrobacterium mediated transformation in Hevea callus and tobacco. GUS gene expression was noticed in Hevea callus indicating that all the promoters are functional. The transgenic tobacco plants showed no GUS gene expression. The implication of these novel promoter regions to co-ordinate the β-1,3-glucanase gene expression can be utilized for defense specific gene expression in future genetic transformation attempts in Hevea and in a wide variety of plant systems.Keywords: abnormal leaf fall, Hevea brasiliensis, Phytophthora, PR-protein, systemic acquired resistance (SAR), β-1,3-glucanase</p

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Parent-implemented interventions for children with developmental disabilities and delays : challenging behavior and parenting stress.

In Study 1, we synthesized the current literature on challenging behavior interventions in community settings and evaluated the intervention effects using the What Works Clearinghouse Single-Case Design Standards (WWC, 2020). The systematic literature review identified 16 studies that evaluated the efficacy of challenging behavior intervention in community settings for children with developmental disabilities. The majority of the studies implemented the challenging behavior interventions in food-based settings (e.g., restaurants and cafeterias), and parents were the primary implementers of these interventions. Of 23 experiments, only one experiment met WWC SCD Standards. In Study 2, we evaluated the effect of parent-implemented functional communication training (FCT) for three participants using a nonconcurrent multiple baseline design. We coached parents of children with developmental delays to implement FCT in the home via telehealth. The study results showed that the parents accurately implemented the assessment and intervention procedures with coaching via telehealth. In addition, parent-implemented FCT effectively reduced challenging behavior and increased manding. In Study 3, we examined the correlation between the Total Stress score, Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child subscales of the Parenting Stress Index-4-Short Form (PSI-4-SF) and the Daily Living Skills domain, Internalizing subdomain, Externalizing subdomain, and Critical Items subdomain of the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3). We also examined the correlation between the PSI-4-SF subscales and the child’s age. Finally, we examined whether scores on PSI-4-SF subscales differed based on child diagnosis and family’s socioeconomic status (SES). The study results showed that higher scores on the Externalizing subdomain of the Vineland-3 were significantly correlated with higher scores on the Parent-Child Dysfunctional Interaction subscale of the PSI-4-SF. In addition, higher scores on the Internalizing subdomain of the Vineland-3 were significantly correlated with higher scores on the Difficult Child subscale of the PSI-4-SF. Finally, the Total Stress score and scores on the Difficult Child subscale of the PSI-4-SF differed significantly between the two SES groups. However, due to the relatively small sample size (i.e., 20 families), the results should be interpreted with caution, and there is a need for additional research

Sinonasal Neuroendocrine Carcinoma in a Young Female – A Case Report

Sinonasal Neuroendocrine Carcinoma (SNEC) is a very rare malignancy which is difficult to differentiate from other nasopharyngeal malignancies due to similar morphological characteristics and small biopsy specimen. We report the case of a 35-year-old female who presented with nasal obstruction and recurrent epistaxis. Histopathological examination along with immunohistochemistry for neuroendocrine markers is required for accurate diagnosis

A combined experimental and theoretical study on the formation of a cyclic tetrameric water cluster and a similar type of cyclic cluster in copper(II) Schiff base complexes

Two copper(II) complexes, [CuL1]⋅2H2O (1) and [CuL2]⋅H2O (2) [where H2L1 {= N,N′-bis(3-methoxysalicylidene)propane-1,3-diamine} and H2L2 {=N,N′-bis(3-ethoxysalicylidene)propane-1,3-diamine} are potential hexadentate N2O4 donor compartmental Schiff bases], were synthesized and characterized. In each complex, copper(II) was placed in the inner N2O2 environment, with a four-coordinate distorted square planar environment keeping the outer O4 compartment pendant. Lattice water molecules were hydrogen bonded with the pendant O4 compartments of the Schiff base ligands. Both complexes formed self-assembled dimers via chelate ring⋅⋅⋅chelate ring and C–H⋅⋅⋅π interactions. A cyclic tetrameric water cluster was stabilized by the oxygen rich region of the Schiff-base ligand in complex 1. A similar type of cyclic cluster involving two water molecules was also observed in complex 2. These supramolecular assemblies were analysed via a DFT study at the M06-2X/def2-TZVP level of theory