Participatory Process for Implementing a Colorectal Cancer Screening Intervention: an Action Plan for Local Sustainability

Background: Rigid protocols can hamper translation of evidence-based interventions from research to real-world settings. This investigation aimed to develop procedures for modifying the study protocol of a community-based participatory research (CBPR) project and to analyze the theoretical constructs that underlie this process. Methods: The research project is a dissemination and implementation study of the Educational Program to Increase Colorectal Cancer Screening (EPICS), an evidence-based intervention targeting African Americans in the United States. The study is being conducted in a partnership with community coalitions in 15 different cities. Each site initially presented unique issues that required modification of the study protocol. Results: In order to honor underlying CBPR theory, it was necessary to negotiate protocol changes with the community coalition at each site, while insuring preservation of the core elements of the intervention. Conclusions: We discuss the ways in which this represents a narrowing of the gap between CBPR and traditional research approaches

Sheep Updates 2005 - Part 2

This session covers seven papers from different authors: CONCURRENT SESSIONS - STRATEGIC MANAGEMENT 1.Finishing Pastoral Lambs, Peter Tozer, Patricia Harper, Janette Drew, Department of Agriculture Western Australia 2. Coating Improves Wool Quality under Mixed Farming Conditions, KE Kemper, ML Hebart, FD Brien, KS Grimson, DH Smith AMM Ramsay, South Australian Research and Development Institute 3. J. S. Richards, K.D. Atkins, T. Thompson, W. K. Murray, Australian Sheep Industry Co-operative Research Centre and NSW Department of Primary Industries, Orange Agricultural Institute, Forest Rd. Orange 4. Strategic Risk Management in the Sheep Industry, J.R.L. Hall, ICON Agriculture (JRL Hall & Co) 5. Joining Prime Lambs for the Northern End of the Market - a Systems Approach, Chris Carter, Peter Tozer, Department of Agriculture Western Australia 6. Lifetime Wool - Dry feed budgeting tool, Mike Hyder, department of Agriculture Western Australia, John Young, Farming Systems Analysis Service, Kojonup, Western Australia 7. Influence of ultrafine wool fibre curvature and blending with cashmere on attributes of knitwear, B. A. McGregor, Primary Industries Research Victoria, Department of Primary Industries, Victori

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Proprioceptive Movement Illusions Due to Prolonged Stimulation: Reversals and Aftereffects

Background. Adaptation to constant stimulation has often been used to investigate the mechanisms of perceptual coding, but the adaptive processes within the proprioceptive channels that encode body movement have not been well described. We investigated them using vibration as a stimulus because vibration of muscle tendons results in a powerful illusion of movement. Methodology/Principal Findings. We applied sustained 90 Hz vibratory stimulation to biceps brachii, an elbow flexor and induced the expected illusion of elbow extension (in 12 participants). There was clear evidence of adaptation to the movement signal both during the 6-min long vibration and on its cessation. During vibration, the strong initial illusion of extension waxed and waned, with diminishing duration of periods of illusory movement and occasional reversals in the direction of the illusion. After vibration there was an aftereffect in which the stationary elbow seemed to move into flexion. Muscle activity shows no consistent relationship with the variations in perceived movement. Conclusion. We interpret the observed effects as adaptive changes in the central mechanisms that code movement in direction-selective opponent channels

Alpha-Linolenic Acid: Is It Essential to Cardiovascular Health?

There is a large body of scientific evidence that has been confirmed in randomized controlled trials indicating a cardioprotective effect for omega-3 fatty acids from fish. For alpha-linolenic acid (ALA), which is the omega-3 fatty acid from plants, the relation to cardiovascular health is less clear. We reviewed the recent literature on dietary ALA intake, ALA tissue concentrations, and cardiovascular health in humans. Short-term trials (6–12 weeks) in generally healthy participants mostly showed no or inconsistent effects of ALA intake (1.2–3.6 g/d) on blood lipids, low-density lipoprotein oxidation, lipoprotein(a), and apolipoproteins A-I and B. Studies of ALA in relation to inflammatory markers and glucose metabolism yielded conflicting results. With regard to clinical cardiovascular outcomes, there is observational evidence for a protective effect against nonfatal myocardial infarction. However, no protective associations were observed between ALA status and risk of heart failure, atrial fibrillation, and sudden death. Findings from long-term trials of ALA supplementation are awaited to answer the question whether food-based or higher doses of ALA could be important for cardiovascular health in cardiac patients and the general population

Artemisone and artemiside - potent pan-reactive antimalarial agents that also synergize redox imbalance in P. falciparum transmissible gametocyte stages

The emergence of resistance towards artemisinin combination therapies (ACTs) by the malaria parasite Plasmodium falciparum has the potential to severely compromise malaria control. Therefore, development of new artemisinins in combination with new drugs that impart activities towards both intraerythrocytic proliferative asexual and transmissible gametocyte stages, in particular those of resistant parasites, are urgently required. We define artemisinins as oxidant drugs through their ability to oxidize reduced flavin cofactors of flavin disulfide reductases critical for maintaining redox-homeostasis in the malaria parasite. Here we compare the activities of 10-amino artemisinin derivatives towards the asexual and gametocyte stages of P. falciparum parasites. Of these, artemisone and artemiside inhibited asexual and gametocyte stages, particularly stage V gametocytes in the low nM range. Further, treatment of both early and late gametocyte stages with artemisone or artemiside combined with the pro-oxidant redox partner methylene blue displays notable synergism. These data suggest that modulation of redox-homeostasis likely is an important druggable process, particularly in gametocytes, and thereby enhances the prospect of using combinations of oxidant and redox drugs for malaria control.The South African Medical Research Council (MRC) Flagship Project MALTB-Redox with funds from the National Treasury under its Economic Competitiveness and Support Package to Richard K. Haynes; a South African MRC Strategic Health Innovation Partnership (SHIP) grant, a South African MRC Collaborative Centre for Malaria Research grant, and a South African National Research Foundation grant (UID 84627) to Lyn-Marie Birkholtz; and South African National Research Foundation grants to Richard K. Haynes (UIDs 90682 and 98934). Donatella Taramelli and Sarah D'Alessandro acknowledge the support from the Global Health Program of the Bill & Melinda Gates Foundation (grant OPP1040394 to Donatella Taramelli, Pietro Alano coordinator, and COST Action CM1307).http://aac.asm.org2019-02-01hj2018Biochemistr

Ectopic T Cell Receptor-α Locus Control Region Activity in B Cells Is Suppressed by Direct Linkage to Two Flanking Genes at Once

The molecular mechanisms regulating the activity of the TCRα gene are required for the production of the circulating T cell repertoire. Elements of the mouse TCRα locus control region (LCR) play a role in these processes. We previously reported that TCRα LCR DNA supports a gene expression pattern that mimics proper thymus-stage, TCRα gene-like developmental regulation. It also produces transcription of linked reporter genes in peripheral T cells. However, TCRα LCR-driven transgenes display ectopic transcription in B cells in multiple reporter gene systems. The reasons for this important deviation from the normal TCRα gene regulation pattern are unclear. In its natural locus, two genes flank the TCRα LCR, TCRα (upstream) and Dad1 (downstream). We investigated the significance of this gene arrangement to TCRα LCR activity by examining transgenic mice bearing a construct where the LCR was flanked by two separate reporter genes. Surprisingly, the presence of a second, distinct, reporter gene downstream of the LCR virtually eliminated the ectopic B cell expression of the upstream reporter observed in earlier studies. Downstream reporter gene activity was unaffected by the presence of a second gene upstream of the LCR. Our findings indicate that a gene arrangement in which the TCRα LCR is flanked by two distinct transcription units helps to restrict its activity, selectively, on its 5′-flanking gene, the natural TCRα gene position with respect to the LCR. Consistent with these findings, a TCRα/Dad1 locus bacterial artificial chromosome dual-reporter construct did not display the ectopic upstream (TCRα) reporter expression in B cells previously reported for single TCRα transgenes

Omega-6 Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of Individual-Level Data for 39 740 Adults from 20 Prospective Cohort Studies

Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods: We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings: Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m(2), who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72,

Creating Indigenous Discourse: History, Power, and Imperialism in Academia, Palestinian Case

This article examines the impossibilities of implementing decolonizing research for indigenous scholars. In addition, it articulates the relationship between a decolonizing research approach and the historical and current forms of academic imperialism; a prototype of the Palestinian legacy is presented. The author argues that the current indigenous discourse is a remnant of oppression. The existing indigenous discourse is not due to the original quest but instead, it is in response to oppression. Also, the author explains the struggles of some indigenous scholars in complying with the reporting and ownership of knowledge that is required by Cartesian principles.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Legionella pneumophila Secretes a Mitochondrial Carrier Protein during Infection

The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionella nucleotide carrier Protein (LncP), encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms