Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo

Mammalian Genome - Intracellular calcium is critical in orchestrating neuronal excitability and analgesia. Carbonic anhydrase-8 (CA8) regulates intracellular calcium signaling through allosteric...     

The DNA Replication,Repair, and Recombination Pathway Genes Modulating Yield and Stress Tolerance Traits in Chickpea

DNA replication, repair, and recombination (DRRR) are the fundamental processes required for faithful transmission of genetic information within and between generations. The DRRR genes protect the cells from potential mutations and damage during the developmental phases and stress conditions. Thus, these genes indirectly regulate diverse important agronomic traits in a crop plant. A genome-wide survey of six DRRR pathway genes, namely, DNA replication, Base Excision Repair, Nucleotide Excision Repair, Homologous Recombination, Mismatch Excision Repair, and Non-Homologous End-Joining, identified 157 DRRR genes in chickpea. Phylogenetic analysis of these genes within the legume clades and model plant Arabidopsis identified 42 conserved DRRR genes exhibiting clade-specific evolutionary patterns. Integrating the gene-based association mapping with differential expression profiling identified the natural alleles of the potential DRRR genes, primarily regulating flowering and maturation time and involved in drought tolerance of chickpea. Identifying and understanding DRRR genes’ roles in regulating yield and stress tolerance traits in a vital grain legume like chickpea is requisite for its future crop improvement endeavors. Manipulation of promising functionally relevant DRRR genes will pave the way for simultaneous improvement in multiple beneficial agronomic traits in chickpea.

     

„Cellules de thyroïdectomie“ et „cellules de castration“ chez la Caille japonaise,Coturnix coturnix japonica

Résumé On compare l'ultrastructure et la localisation des phosphatases acides au niveau des cellules hypophysaires delta et beta, chez des Cailles mâles thyroïdectomisées et maintenues en photopériode courte ou bien castrées, puis placées en photopériode longue. On étudie en outre, dans ces deux cas, les effets d'injections de doses croissantes de thyroxine.La thyroïdectomie provoque la transformation des cellules delta en cellules de thyroïdectomie groupées en îlots à la périphérie du lobe céphalique. Ces cellules sont pauvres en phosphatases acides. La thyroxine (10 g/j pendant 2 jours) provoque la régression de ces cellules et l'apparition de lysosomes. Les cellules beta ne sont pas modifiées par la thyroïdectomie.La castration-photostimulation stimule les cellules beta localisées dans le lobe céphalique. Elle provoque dans les deux lobes de la glande l'hypertrophie et la vacuolisation des cellules delta qui se distinguent des cellules de thyroïdectomie par la présence de nombreux lysosomes. La thyroxine freine simultanément l'activation des cellules delta et des cellules beta, en provoquant la formation de lysosomes, mais la dose efficace chez le mâle photostimulé (20 g et 60 g/j pendant 5 jours) est sans effet chez le castrat photostimulé (dose efficace 180 g/j).Pour interpréter ces faits, on admet que les cellules delta, thyréotropes et les cellules beta, gonadotropes, seraient simultanément soumises à un contrôle freinateur des hormones thyroïdiennes et des stéroïdes mâles.

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Thyroidectomy cells and castration cells in the Japanese quail, Coturnix coturnix japonica Ultrastructure and cytoenzymology

Summary The ultrastructure and the localization of acid-phosphatase activity are compared in beta and delta pituitary cells of male Japanese quail, either thyroidectomized and maintained in short days, or castrated then put in long days. Moreover, in these two cases, the effects of brief treatments with increasing doses of thyroxine are studied.Thyroidectomy induces transformation of delta cells into thyroidectomy cells arranged in clumps at the periphery of the cephalic lobe. The acid-phosphatase activity of such cells is low. Thyroxine (10 g per day for two days) causes regression of these cells and the appearance of numerous lysosomes. Beta cells are not modified by thyroidectomy.Castration and exposure to long days stimulate beta cells, localized in the cephalic lobe. It induces, also, in both pituitary lobes, hypertrophy and vacuolization of delta cells which differ from thyroidectomy cells by the presence of numerous lysosomes.Thyroxine in photostimulated quail inhibits both delta- and beta-cell stimulation and increases the frequency of lysosomes but the effective doses on males (20 g or 60 g per day for five days) are inactive on castrates, the response of which is obtained with 180 g per day.In order to explain these data, a hypothesis is suggested: Thyrotropic delta cells and gonadotropic beta cells are both subject to a double inhibiting control by thyroid hormones and male steroids.

Nous remercions très vivement pour leur excellente collaboration technique Mme Renée Picart (préparation des tissus pour la microscopie électronique) et M. Claude Pennarun (photographe).     

Escherichia coli biofilm: development and therapeutic strategies

Escherichia coli biofilm consists of a bacterial colony embedded in a matrix of extracellular polymeric substances (EPS) which protects the microbes from adverse environmental conditions and results in infection. Besides being the major causative agent for recurrent urinary tract infections, E. coli biofilm is also responsible for indwelling medical device‐related infectivity. The cell‐to‐cell communication within the biofilm occurs due to quorum sensors that can modulate the key biochemical players enabling the bacteria to proliferate and intensify the resultant infections. The diversity in structural components of biofilm gets compounded due to the development of antibiotic resistance, hampering its eradication. Conventionally used antimicrobial agents have a restricted range of cellular targets and limited efficacy on biofilms. This emphasizes the need to explore the alternate therapeuticals like anti‐adhesion compounds, phytochemicals, nanomaterials for effective drug delivery to restrict the growth of biofilm. The current review focuses on various aspects of E. coli biofilm development and the possible therapeutic approaches for prevention and treatment of biofilm‐related infections.     

Modification of Rifamycin Polyketide Backbone Leads to Improved Drug Activity against Rifampicin-resistant Mycobacterium tuberculosis

Rifamycin B, a product of Amycolatopsis mediterranei S699, is the precursor of clinically used antibiotics that are effective against tuberculosis, leprosy, and AIDS-related mycobacterial infections. However, prolonged usage of these antibiotics has resulted in the emergence of rifamycin-resistant strains of Mycobacterium tuberculosis. As part of our effort to generate better analogs of rifamycin, we substituted the acyltransferase domain of module 6 of rifamycin polyketide synthase with that of module 2 of rapamycin polyketide synthase. The resulting mutants (rifAT6::rapAT2) of A. mediterranei S699 produced new rifamycin analogs, 24-desmethylrifamycin B and 24-desmethylrifamycin SV, which contained modification in the polyketide backbone. 24-Desmethylrifamycin B was then converted to 24-desmethylrifamycin S, whose structure was confirmed by MS, NMR, and X-ray crystallography. Subsequently, 24-desmethylrifamycin S was converted to 24-desmethylrifampicin, which showed excellent antibacterial activity against several rifampicin-resistant M. tuberculosis strains.     

Genome Sequence of Acinetobacter sp. Strain HA, Isolated from the Gut of the Polyphagous Insect Pest Helicoverpa armigera

In this study, Acinetobacter sp. strain HA was isolated from the midgut of a fifth-instar larva of Helicoverpa armigera. Here, we report the draft genome sequence (3,125,085 bp) of this strain that consists of 102 contigs, 2,911 predicted coding sequences, and a G+C content of 41%.     

Higher Prevalence of Human Papillomavirus Infection in Adolescent and Young Adult Girls Belonging to Different Indian Tribes with Varied Socio-Sexual Lifestyle

BackgroundDespite high prevalence of human papillomavirus (HPV) infection and cervical cancer in Indian women, no study has been done in tribal populations whose socio-sexual lifestyle is different. Therefore, HPV screening has been carried out in pre-adolescent, adolescent and young adult tribal girls using self-collected urine samples.Methods20–35 ml self-collected midstream urine samples were obtained from a total of 2278 healthy tribal girls (9–25 years) comprising pre-adolescent, adolescent and young adults from three Indian states: Madhya Pradesh, Jharkhand and Chhattisgarh. β-globin positive 2034 samples were employed for HPV detection and genotyping.ResultsThe overall prevalence of HPV infection in tribal girls was 12.9% (262/2034). More than 65% (172/262) of them were infected with HR-HPV types of which HPV16 was the most predominant type (54%). Young adult girls aged 18–25 years showed a significantly higher prevalence of HPV infection (19.2%; OR = 3.36; 95% CI 2.97–6.34, P<0.001) as compared to that in adolescent (11.4%; OR = 1.82; 95% CI 1.20–2.76, P<0.01) or pre-adolescent girls (6.6%).ConclusionThis is a first study showing significantly a very high prevalence of HPV infection in adolescent and young adult tribal girls possibly due to different socio-sexual behavior, indicating a serious health concern for Indian tribal women.     

CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration

Age related macular degeneration (AMD) is a progressive, neurodegenerative disorder that leads to the severe loss of central vision in elderlies. The health of retinal pigment epithelial (RPE) cells is critical for the onset of AMD. Chronic oxidative stress along with loss of lysosomal activity is a major cause for RPE cell death during AMD. Hence, development of a molecule for targeted lysosomal delivery of therapeutic protein/drugs in RPE cells is important to prevent RPE cell death during AMD. Using human RPE cell line (ARPE-19 cells) as a study model, we confirmed that hydrogen peroxide (H₂O₂) induced oxidative stress results in CD44 cell surface receptor overexpression in RPE cells; hence, an important target for specific delivery to RPE cells during oxidative stress. We also demonstrate that the known nucleic acid CD44 aptamer - conjugated with a fluorescent probe (FITC) - is delivered into the lysosomes of CD44 expressing ARPE-19 cells. Hence, as a proof of concept, we demonstrate that CD44 aptamer may be used for lysosomal delivery of cargo to RPE cells under oxidative stress, similar to AMD condition. Since oxidative stress may induce wet and dry AMD, both, along with proliferative vitreoretinopathy, CD44 aptamer may be applicable as a carrier for targeted lysosomal delivery of therapeutic cargoes in ocular diseases showing oxidative stress in RPE cells.