Identification of differentially expressed genes in breast cancer tissues and cells

Breast cancer, is the second leading cause of cancer related deaths among women in developed countries, and the incidence of morbidity and mortality is rising in developing countries. The purpose of this project was to utilize the differential display technique to identify genetic changes in normal versus malignant breast tissue. It was also used in a defined cell culture system having differential cellular characteristics, to identify genes that may be responsible for different biological behavior of these cell lines. Messenger RNA from normal, breast cancer tissues, and breast tissues from reduction mamoplasty yielded fifty-nine differentially expressed bands representing differentially expressed genes. Northern hybridization analysis proved negative, suggesting that these genes may represent low abundant message. mRNA from two clones; one tumorigenic, and the other non-tumorigenic in nude mice; obtained by stable transfection of galectin-3 gene in a non-tumorigenic BT 549 breast cell line, was analyzed by differential display. Galectin-3, a calcium independent carbohydrate binding protein has been shown to be involved in many biological processes, but its exact function is still unclear. A 607 bp fragment was differentially expressed by the tumorigenic clone, and DNA sequence of which revealed a 93% homology with the human Line 1 retrotransposon (Ll). Ll is a poly-A mobile element, and its insertion into functional genes has been implicated in human diseases, including breast cancer, however its role in breast cancer is not clear. To determine the locale and expression of galectin-3 and L1 in normal versus tumor tissues, immunohistochemical analysis of breast carcinoma specimens, fibrocystic, normal breast tissues, and the tumorigenic clone of BT 549, 11-9-1-4, was performed. L1 and galectin-3 was found to be co-localized, and the imrnuno-staining was most intense in tumor tissue, and was minimal in normal tissue. Staining was significantly correlated with disease progression and tumor recurrence, suggesting that the expression of galectin-3 and L1 may represent a new mechanism by which breast tumor cells acquire aggressive phenotype. However, the interaction of L1 and galectin-3, if any, and their influence on tumor development and progression remains to be determined

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Learning the Rules of the Game – How Health and Social Care Students Learn to Learn

This document is the Accepted Manuscript version of a Published Work that appeared in final form in [British Journal of Nursing], copyright © MA Education, after peer review and technical editing by the publisher. To access the final edited and published work see [https://www.magonlinelibrary.com/doi/full/10.12968/bjon.2023.32.9.404].Learning the rules of the game: how health and social care students learn to learn - commentar

Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

10.1016/j.ajhg.2013.01.002American Journal of Human Genetics924489-503AJHG

A genomic catalog of Earth’s microbiomes

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes.</p