Synthesis of novel indole substituted heterocyclics

51-59Herein is reported the synthesis of a series (21 number) of novel hybrid molecules composed of an indole-3-carbaldehyde attached to triazole/ isoxazole/ isoxazoline moieties having various aromatic/benzylic/aliphatic substitutions via 1,3-dipolar cycloaddition between azide/ nitrile oxide (dipole) and indole substituted alkyne/ alkene (dipolarophile) based on the importance of indole, 1,2,3-triazole, isoxazole and isoxazoline containing pharmacophores

Political branding: sense of identity or identity crisis? An investigation of the transfer potential of the brand identity prism to the UK Conservative Party

Brands are strategic assets and key to achieving a competitive advantage. Brands can be seen as a heuristic device, encapsulating a series of values that enable the consumer to make quick and efficient choices. More recently, the notion of a political brand and the rhetoric of branding have been widely adopted by many political parties as they seek to differentiate themselves, and this has led to an emerging interest in the idea of the political brand. Therefore, this paper examines the UK Conservative Party brand under David Cameron’s leadership and examines the applicability of Kapferer’s brand identity prism to political branding. This paper extends and operationalises the brand identity prism into a ‘political brand identity network’ which identifies the inter-relatedness of the components of the corporate political brand and the candidate political brand. Crucial for practitioners, this model can demonstrate how the brand is presented and communicated to the electorate and serves as a useful mechanism to identify consistency within the corporate and candidate political brands

A novel HSF4 gene mutation (p.R405X) causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan

<p>Abstract</p> <p>Background</p> <p>Hereditary cataracts are most frequently inherited as autosomal dominant traits, but can also be inherited in an autosomal recessive or X-linked fashion. To date, 12 loci for autosomal recessive cataracts have been mapped including a locus on chromosome 16q22 containing the disease-causing gene <it>HSF4 </it>(Genbank accession number <ext-link ext-link-id="NM_001040667" ext-link-type="gen">NM_001040667</ext-link>). Here, we describe a family from Pakistan with the first nonsense mutation in <it>HSF4 </it>thus expanding the mutational spectrum of this heat shock transcription factor gene.</p> <p>Methods</p> <p>A large consanguineous Pakistani family with autosomal recessive cataracts was collected from Quetta. Genetic linkage analysis was performed for the common known autosomal recessive cataracts loci and linkage to a locus containing <it>HSF4 </it>(OMIM 602438) was found. All exons and adjacent splice sites of the heat shock transcription factor 4 gene (<it>HSF4</it>) were sequenced. A mutation-specific restriction enzyme digest (H<it>ph</it>I) was performed for all family members and unrelated controls.</p> <p>Results</p> <p>The disease phenotype perfectly co-segregated with markers flanking the known cataract gene HSF4, whereas other autosomal recessive loci were excluded. A maximum two-point LOD score with a Zmax = 5.6 at θ = 0 was obtained for D16S421. Direct sequencing of HSF4 revealed the nucleotide exchange c.1213C > T in this family predicting an arginine to stop codon exchange (p.R405X).</p> <p>Conclusion</p> <p>We identified the first nonsense mutation (p.R405X) in exon 11 of <it>HSF4 </it>in a large consanguineous Pakistani family with autosomal recessive cataract.</p

Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

<p>Abstract</p> <p>Background</p> <p>To identify the genetic defect associated with autosomal recessive congenital cataract (ARCC), mental retardation (MR) and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families.</p> <p>Methods</p> <p>We screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes <it>PAX6</it>, <it>PITX3 </it>and <it>HSF4 </it>are expressed in human brain and one gene <it>LIM2 </it>encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development. All genes were screened by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly.</p> <p>Results</p> <p>We report no mutation in the four genes of congenital cataract and its flanking regions. Only variations that did not segregate with the studied phenotypes (ARCC associated to MR, ARCC associated with MR and microcephaly) are reported. We detected three intronic variations in <it>PAX6 </it>gene: IVS4 -274insG (intron 4), IVS12 -174G>A (intron12) in the four studied families and IVS4 -195G>A (intron 4) in two families. Two substitutions polymorphisms in <it>PITX3 </it>gene: c.439 C>T (exon 3) and c.930 C>A (exon4) in one family. One intronic variation in <it>HSF4 </it>gene: IVS7 +93C>T (intron 7) identified in one family. And three intronic substitutions in <it>LIM2 </it>gene identified in all four studied families: IVS2 -24A>G (intron 2), IVS4 +32C>T (intron 4) and c.*15A>C (3'-downstream sequence).</p> <p>Conclusion</p> <p>Although the role of the four studied genes: <it>PAX6</it>, <it>PITX3</it>, <it>HSF4 </it>and <it>LIM2 </it>in both ocular and central nervous system development, we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, MR and microcephaly.</p

Synthesis of novel indole substituted heterocyclics

Herein is reported the synthesis of a series (21 number) of novel hybrid molecules composed of an indole-3-carbaldehyde attached to triazole/ isoxazole/ isoxazoline moieties having various aromatic/benzylic/aliphatic substitutions via 1,3-dipolar cycloaddition between azide/ nitrile oxide (dipole) and indole substituted alkyne/ alkene (dipolarophile) based on the importance of indole, 1,2,3-triazole, isoxazole and isoxazoline containing pharmacophores

Grafting Bell Pepper onto Local Genotypes of <i>Capsicum</i> spp. as Rootstocks to Alleviate Bacterial Wilt and Root-Knot Nematodes under Protected Cultivation

In soil-based protected cultivation, the prevalence of certain diseases like bacterial wilt and nematodes in the bell pepper plant due to its successive cropping pose a threat for maximizing productivity. Considering the potential of grafting to alleviate various biotic and abiotic stresses, often relying on rootstock’s capability, we explored the potential of diverse local genotypes of Capsicum spp. to utilize as rootstocks. In this research, we assessed the performance of a commercial bell pepper cv. Massilia F1, grafted onto twenty-five rootstocks along with non-grafted and self-grafted Massilia plants under artificial inoculation conditions of bacterial wilt (Ralstonia solanacearum) and nematodes (Meloidogyne incognita) in a plastic greenhouse. The response of rootstock grafting was determined by assessing disease incidences and their effect on plants growth, yield, and physiology, as well as their efficiency in nutrient accumulation. The grafted plants exhibited varied responses to diseases depending on rootstock genotypes. Notably, Massilia grafted onto the CRS-8 and CRS-1 rootstocks exhibited high bacterial wilt resistance by showing lower percent disease incidence (PDI) (22.22 and 27.78 percent, respectively). Others, like CRS-11, CRS-12, CRS-13, CRS-21, and CRS-24, showed moderate resistance (PDI ranging from 33.33 to 38.89 percent, respectively). The self-grafted and non-grafted plants were highly susceptible and recorded complete mortality by the end of the experiment. All of the grafted plants exhibited promising resistance against nematode infestation compared to non-grafted and self-grafted plants with 26.17 and 8.67 percent root galls, respectively. The susceptible plants had lower shoot and root dry weights, while the resistant graft combinations had comparatively higher biomass. Importantly, grafting induced earliness in flowering and provided higher yields, especially in graft combinations involving the CRS-15, CRS-11, and CRS-8 rootstocks. These graft combinations exhibited significantly higher yields over the non-grafted and self-grafted plants. The plant yield was positively associated with plant height, number of leaves, fresh and dry weight of roots, number of fruits per plant, and average fruit weight, but negatively related to bacterial wilt and root-knot nematode incidences. The increased level of antioxidant enzymes such as polyphenol oxidase (PPO), phenylalanine ammonia lyase (PAL), and peroxidase (POD) and the higher total chlorophyll content in the resistant grafted plants indicates their better ability to cope with diseases at the cellular level. This study highlights the robust performance of certain rootstocks from Capsicum annuum (CRS-1, CRS-2, CRS-11, CRS-15) and Capsicum frutescens (CRS-8, CRS-13, CRS-22) species across multiple measured parameters. Grafting emerges as a sustainable solution for bell pepper production in bacterial wilt- and nematode-infested soil under plastic greenhouses