The Effect of COVID-19 on Independent African Churches (IACs) in Johannesburg, South Africa

This paper explores the effect of the COVID-19 pandemic on the religious tourism activities of the four most prominent Independent Apostolic Churches (IAC) operating in Johannesburg, South Africa. This is an interpretive qualitative research study based on data from 15 telephone-based semi-structured interviews with congregants and church leaders of the Zion Christian Church, Zimbabwe (ZCC Mutendi), The Apostolic Church of Johane Marange, The Apostolic Church of Johane Masowe and Apostolic Faith Church, Mugodhi. Thematic content analysis was used for data analysis. The COVID-19 pandemic has negatively impacted the religious tourism activities of all four IACs in the study as they accepted and implemented various aspects of the lockdown regulations. The cancellation of their main annual events and weekly and monthly activities combined with a considerable reduction in contribution from their members resulted in churches’ inability to finance their main activities, i.e. their healing camps. It is evident that the ripple effects of reduced IAC activities in and around Johannesburg has negatively affected the city’s income from churches’ religious tourism activities. This is the first study to explore the activities of IACs in Johannesburg (and Africa) before and during the pandemic, pointing to churches’ significant contribution to religious tourism in the city

Patient Perspective on the Value of Genetic Counselling for Familial Pancreas Cancer

<p>Abstract</p> <p>Purpose</p> <p>To assess patient views regarding the value of genetic counselling for familial pancreas cancer in the absence of predictive genetic testing.</p> <p>Patients and methods</p> <p>At-risk adults with three or more relatives with pancreas cancer received genetic counselling prior to research screening via endoscopic ultrasound. Questionnaires were mailed after the visit to assess perceived value of the counselling session.</p> <p>Results</p> <p>Ninety-three percent of respondents felt genetic counselling for pancreas cancer was helpful despite the lack of a causative gene, while only 7% felt that it should not be offered until such a gene is discovered. Over half of respondents believed the pancreas cancer in their family was caused by a gene mutation, and 42% thought they had inherited the mutation. The average perceived lifetime risk of developing pancreas cancer was 51%, and 87% of respondents would ultimately seek predictive genetic testing. When more information is gained, 89% would be interested in another genetic counselling session, and 82% would recommend current genetic counselling for pancreas cancer to a friend or relative with a family history of the disease.</p> <p>Conclusion</p> <p>Despite the lack of an identified major causative gene for pancreas cancer, respondents found genetic counselling for this malignancy to be helpful. These patients perceive their personal cancer risk to be high, and would seek predictive genetic testing if it were available. Referral for genetic counselling should be offered to appropriate individuals.</p

The human aquaporin-CHIP gene. Structure, organization, and chromosomal localization

Aquaporin-CHIP is the first known molecular water channel. Originally identified in red cells and renal tubules, transcripts and proteins related to AQP-CHIP are also expressed in diverse epithelia with distinct developmental patterns. Northern analyses of RNA from several tissues revealed transcripts of 3.1 kilobases and other sizes. The nucleotide sequences of human kidney AQP-CHIP cDNAs are identical to the human bone marrow AQP-CHIP cDNA. The 17-kilobase human AQP-CHIP structural gene was isolated, and restriction maps were constructed and partially sequenced. The TATA consensus sequence is located 87 bp 5' to the translation initiation site, and sequences surrounding the polyadenylation consensus were determined. Four exons were identified corresponding to amino acids 1-128, 129-183, 184-210, and 211-269, separated by introns of 9.6, 0.43, and 0.80 kilobases. Genomic Southern analyses indicated the existence of a single AQP-CHIP gene which was located at human chromosome 7p14 by in situ hybridization. Sequence comparisons of AQP-CHIP and cDNAs of similar proteins from diverse species suggested a common evolutionary origin. At least three of these proteins are now known to function as membrane water pores and are referred to as the "Aquaporins." These genomic AQP-CHIP DNA sequences should permit molecular characterization of the complex patterns of AQP-CHIP expression

The human Aquaporin-5 gene. Molecular characterization and chromosomal localization.

The cDNA for the fifth mammalian aquaporin (AQP5) was isolated from rat, and expression was demonstrated in rat salivary and lacrimal glands, cornea, and lung (Raina, S., Preston, G. M., Guggino, W. B., and Agre, P. (1995) J. Biol. Chem. 270, 1908-1912). Here we report the isolation and characterization of the human AQP5 cDNA and gene. The AQP5 cDNA from a human submaxillary gland library contains a 795-base pair open reading frame encoding a 265-amino acid protein. The deduced amino acid sequences of human and rat AQP5 are 91% identical with 6 substitutions in the 22-amino acid COOH-terminal domain. Expression of human AQP5 in Xenopus oocytes conferred mercurial-sensitive osmotic water permeability (Pf) equivalent to other aquaporins. The human AQP5 structural gene resides within a 7. 4-kilobase SalI-EcoRI fragment with four exons corresponding to amino acids 1-121, 122-176, 177-204, and 205-265 separated by introns of 1.2, 0.5, and 0.9 kilobases. A transcription initiation site was identified 518 base pairs upstream of the initiating methionine. Genomic Southern analysis indicated that AQP5 is a single copy gene which localized to human chromosome 12q13; this coincides with the chromosomal locations of the homologous human genes MIP and AQP2, thus confirming 12q13 as the site of an aquaporin gene cluster. The mouse gene localized to distal chromosome 15. This information may permit molecular characterization of AQP5 expression during normal development and in clinical disorders

Protected Areas and Nature Recovery: Achieving the goal to protect 30% of UK land and seas for nature by 2030

This report from the British Ecological Society (published 22 April 2022) examines the Prime Minister’s pledge to protect 30% of UK land and seas by 2030 to support nature recovery

Activating mutation in MET oncogene in familial colorectal cancer

<p>Abstract</p> <p>Background</p> <p>In developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The <it>MET </it>proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility.</p> <p>Methods</p> <p><it>MET </it>exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies). Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C <b>></b>T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors.</p> <p>Results</p> <p>Here we report a germline non-synonymous change in the <it>MET </it>proto-oncogene at amino acid position T992I (also reported as <it>MET </it>p.T1010I) in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in <1% in the general population. The threonine at amino acid position 992 lies in the tyrosine kinase domain of MET and a change to isoleucine at this position has been shown to promote metastatic behavior in cell-based models. The average age of CRC diagnosis in patients in this study is 63 years in mutation carriers, which is 8 years earlier than the general population average for CRC.</p> <p>Conclusions</p> <p>Although the <it>MET </it>p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this <it>MET </it>genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will be an important extension of this work to define the clinical significance.</p

Long-term risk of medical conditions associated with breast cancer treatment

Early and late effects of cancer treatment are of increasing concern with growing survivor populations, but relevant data are sparse. We sought to determine the prevalence and hazard ratio of such effects in breast cancer cases

Clinically Relevant Changes in Family History of Cancer Over Time

Knowledge of family cancer history is important for assessing cancer risk and guiding screening recommendations

GATA6 Activates Wnt Signaling in Pancreatic Cancer by Negatively Regulating the Wnt Antagonist Dickkopf-1

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease characterized by late diagnosis and treatment resistance. Recurrent genetic alterations in defined genes in association with perturbations of developmental cell signaling pathways have been associated with PDAC development and progression. Here, we show that GATA6 contributes to pancreatic carcinogenesis during the temporal progression of pancreatic intraepithelial neoplasia by virtue of Wnt pathway activation. GATA6 is recurrently amplified by both quantitative-PCR and fluorescent in-situ hybridization in human pancreatic intraepithelial neoplasia and in PDAC tissues, and GATA6 copy number is significantly correlated with overall patient survival. Forced overexpression of GATA6 in cancer cell lines enhanced cell proliferation and colony formation in soft agar in vitro and growth in vivo, as well as increased Wnt signaling. By contrast siRNA mediated knockdown of GATA6 led to corresponding decreases in these same parameters. The effects of GATA6 were found to be due to its ability to bind DNA, as forced overexpression of a DNA-binding mutant of GATA6 had no effects on cell growth in vitro or in vivo, nor did they affect Wnt signaling levels in these same cells. A microarray analysis revealed the Wnt antagonist Dickopf-1 (DKK1) as a dysregulated gene in association with GATA6 knockdown, and direct binding of GATA6 to the DKK1 promoter was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assays. Transient transfection of GATA6, but not mutant GATA6, into cancer cell lines led to decreased DKK1 mRNA expression and secretion of DKK1 protein into culture media. Forced overexpression of DKK1 antagonized the effects of GATA6 on Wnt signaling in pancreatic cancer cells. These findings illustrate that one mechanism by which GATA6 promotes pancreatic carcinogenesis is by virtue of its activation of canonical Wnt signaling via regulation of DKK1

Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis

Present investigations suggest that approximately 30% of colorectal cancer (CRC) cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with CRC. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high grade dysplasia were enrolled. Known familial CRC syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE's 1100 short tandem repeat marker set at an average 4 cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with MERLIN analysis package. Linkage analysis revealed three genetic regions with NPL LOD scores ≥ 2.0: Ch. 3q29, LOD 2.61 (p=0.0003); Ch. 4q31.3, LOD 2.13 (p=0.0009); and Ch. 7q31.31, LOD 3.08 (p=0.00008). Affected siblings with increased sharing at the 7q31 locus have an 3.8 year (±3.5) earlier age of CRC onset although this is not statistically significant (p=0.11). No significant linkage was found near genes causing known syndromes or, regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21-q24 region reported to be linked in CRC relative pairs, is supported by our study, albeit a minor peak (LOD 0.9, p=0.02). No known familial cancer genes reside in the 7q31 locus, thus the identified region may contain a novel susceptibility gene responsible for common familial CRC