Quantitative analysis of ruminal methanogenic microbial populations in beef cattle divergent in phenotypic residual feed intake (RFI) offered contrasting diets

peer-reviewedBackground Methane (CH4) emissions in cattle are an undesirable end product of rumen methanogenic fermentative activity as they are associated not only with negative environmental impacts but also with reduced host feed efficiency. The aim of this study was to quantify total and specific rumen microbial methanogenic populations in beef cattle divergently selected for residual feed intake (RFI) while offered (i) a low energy high forage (HF) diet followed by (ii) a high energy low forage (LF) diet. Ruminal fluid was collected from 14 high (H) and 14 low (L) RFI animals across both dietary periods. Quantitative real time PCR (qRT-PCR) analysis was conducted to quantify the abundance of total and specific rumen methanogenic microbes. Spearman correlation analysis was used to investigate the association between the relative abundance of methanogens and animal performance, rumen fermentation variables and diet digestibility. Results Abundance of methanogens, did not differ between RFI phenotypes. However, relative abundance of total and specific methanogen species was affected (P < 0.05) by diet type, with greater abundance observed while animals were offered the LF compared to the HF diet. Conclusions These findings suggest that differences in abundance of specific rumen methanogen species may not contribute to variation in CH4 emissions between efficient and inefficient animals, however dietary manipulation can influence the abundance of total and specific methanogen species.Funding for the development and main work of this research was provided under the National Development Plan, through the Research Stimulus Fund, administered by the Department of Agriculture, Fisheries & Food, Ireland RSF 05 224

An identity-based perspective on proactivity: Future work selves and beyond

An identity-based perspective on proactivity: Future work selves and beyon

Business-driven social change:a systematic review of the evidence

How can companies help change people's behaviour in order to benefit society? Organizations have the resources and market influence to effect positive change. Through product labeling, supply chain management, cause marketing, corporate philanthropy, employee volunteerism and NGO (non-government organization) partnerships, companies are helping society get active, eat healthy foods, dispose of products properly, use less energy and generally live more sustainable lives. This report reveals the three conditions necessary for changing people's behaviour that create benefits for society. The report also includes 19 mechanisms companies can use to motivate people to change and to create the capabilities and opportunities for change

Development of Nano- and Microparticle Technologies for Targeted Gene Silencing through RNA Interference Manipulation of the Immune Response in Inflammatory Lung Disease

RNA Interference (RNAi) allows specific and potent knockdown of target genes and interest now lies beyond its use as a molecular biology tool and in its potential as a therapeutic to mediate gene silencing in diseased cells. Targeted local delivery of small interfering RNA (siRNA) to the lungs via inhalation offers a unique opportunity to treat a range of previously unbeatable or poorly controlled respiratory conditions. Alveolar macrophages are the first line of defence against inhaled toxins and pathogens and are essential for the initiation of the inflammatory response. Targeting these cells provides a means of manipulating the immune response of the lungs for the treatment of diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and asthma. However, macrophages are a difficult cell type to transfect. Consequently a delivery system that will enhance uptake as well as specifically target alveolar macrophages would be beneficial for the treatment of respiratory inflammatory conditions and has received notable attention in recent years. Herein we have developed targeted liposomes and microparticles (MP) suitable for inhalation for optimal siRNA delivery to alveolar macrophages. Anionic and mannosylated liposomes and uncoated and gelatin coated poly(lactic-co-glycolic acid) (PLGA) microparticles targeted macrophages via scavenger receptors (SRs), mannose receptors (MRs) and size and charge related phagocytosis, respectively. Mannosylated cholesterol analogues Mann-C2-Chol, Mann-C4-Chol and Mann-C6-Chol, differing in linker lengths, were synthesised and incorporated into neutral liposomes. Formulations of liposomes and microparticles were optimised for efficient siRNA encapsulation and screened for uptake, toxicity and immunogenicity in vitro using high content cell analysis (HCA) methods that were specifically developed. HCA determined uptake of targeted anionic 1,2-dioleoyl-sn-glycero-3- phospho-L-serine (DOPS) and mannosylated (Mann-C6-Chol) composed liposomes between 200 and 400nm and uncoated PLGA microparticles to be optimal in macrophage cells. Significant knockdown of tumour necrosis factor-alpha (TNFa) in lipopolysaccharide (LPS) stimulated cells was mediated via DOPS liposomes and uncoated PLGA microparticles. Additionally, mannosylated liposomes appeared to activate macrophage mannose receptors in a concentration and linker dependent manner and reduce inflammation. In general liposomes and microparticles were non-toxic and non-immunogenic compared to positive controls. However exceptions included high doses of DOPS liposomes which significantly reduced cell viability in RAW 264.7 cells, significantly increased nuclear factor kappa B (NFkB) activity and induced pro-inflammatory cytokines in differentiated THP-1 cells after 24 hours. However, mannosylated liposomes induced a potent inflammatory response in vivo but effects were localised to the lungs, in vivo reductions of TNFa in bronchoalveolar lavage fluid (BALF) following LPS challenge were observed in mice treated with TNFa targeted naked siRNA and encapsulated in mannosylated liposomes

Targeted Liposomal Drug Delivery to Monocytes and Macrophages

As the role of monocytes and macrophages in a range of diseases is better understood, strategies to target these cell types are of growing importance both scientifically and therapeutically. As particulate carriers, liposomes naturally target cells of the mononuclear phagocytic system (MPS), particularly macrophages. Loading drugs into liposomes can therefore offer an efficient means of drug targeting to MPS cells. Physicochemical properties including size, charge and lipid composition can have a very significant effect on the efficiency with which liposomes target MPS cells. MPS cells express a range of receptors including scavenger receptors, integrins, mannose receptors and Fc-receptors that can be targeted by the addition of ligands to liposome surfaces. These ligands include peptides, antibodies and lectins and have the advantages of increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. The goal for targeting monocytes/macrophages using liposomes includes not only drug delivery but also potentially a role in cell ablation and cell activation for the treatment of conditions including cancer, atherosclerosis, HIV, and chronic inflammation

Organizations driving positive social change:a review and an integrative framework of change processes

Academic and practitioner interest in how market-based organizations can drive positive social change (PSC) is steadily growing. This paper helps to recast how organizations relate to society. It integrates research on projects stimulating PSC – the transformational processes to advance societal well-being – which is fragmented across different streams of research in management and related disciplines. Focusing on the mechanisms at play in how organizations and their projects affect change in targets outside of organizational boundaries, we 1) clarify the nature of PSC as a process, 2) develop an integrative framework that specifies two distinct PSC strategies, 3) take stock of and offer a categorization scheme for change mechanisms and enabling organizational practices, and 4) outline opportunities for future research. Our conceptual framework differentiates between surface- and deep-level PSC strategies understood as distinct combinations of change mechanisms and enabling organizational practices. These strategies differ in the nature and speed of transformation experienced by the targets of change projects and the resulting quality (pervasiveness and durability), timing, and reach of social impact. Our findings provide a solid base for integrating and advancing knowledge across the largely disparate streams of management research on Corporate Social Responsibility, Social Entrepreneurship, and Base of the Pyramid, and open up important new avenues for future research on organizing for PSC and on unpacking PSC processes

Pre-Existing Social Conditions: A Call to Prevent the Perpetuation of Gender Inequalities in Research Production during COVID-19

The global COVID-19 pandemic has increased the demand for systematic studies on our changing society and medical students are responding accordingly. However, emerging evidence indicates that there are changing patterns in research production since the initial COVID-19 outbreak in early 2020, with an exponential increase in the number of manuscripts submitted to academic journals for peer review, but with women producing significantly less research compared to men. In an effort to contemplate what academic journals’ responsibilities are to counteract these trends among medical students, we consider three “pre-existing social conditions” that have the potential to negatively affect female medical students’ careers long-term: 1) the unequal division of labor both at home and work; 2) women’s lower well-being compared to men’s; and 3) men’s greater representation in science, technology, engineering, and mathematics (STEM) fields. As a society, we need to offset these trends that threaten women’s careers, as we are at risk of reversing the diligent work achieved to improve gender equality in the fields of science and medicine. While “pre-existing conditions”—the social, economic, political, and historical forces discussed here— have led to, and exacerbated, gender disparities in research production during the pandemic, The International Journal of Medical Students (IJMS) is committed to acknowledging these gender inequalities and preventing their perpetuation among the next generation of future doctors and physician-scientists

Relation between physical activity and oxygen uptake efficiency in men with CVD

Purpose: The oxygen uptake efficiency slope (OUES) represents the rate of increase in V̇O2 in response to a given V̇E during incremental exercise, indicating how effectively oxygen is taken in by the lungs, transported and used in the periphery. OUES, calculated using only submaximal exercise data is identical to the OUES calculated over the entire duration of a cardiopulmonary exercise test (CEPT) , and both maximal and submaximal OUE are significantly related to cardiorespiratory fitness (CRF) measured as V̇O2peak. Currently, little research has been published on how physical activity (PA) assessed by accelerometers is related to submaximal and maximal OUES. The purpose of this study was to determine the relation light (LIPA), moderate (MIPA) and vigorous (VIPA) intensity physical activity and maximal and submaximal OUES in men with cardiovascular disease (CVD). Methods: A total of 56 men (mean ( SD): age of 59.3 ± 9.2 yr., V̇O2 peak (L/min) 2.0 0.50, V̇O2 peak (mL/kg/min) 23.6 5.8, were recruited during an induction to a community-based exercise referral program following completion of phase 2 cardiac rehabilitation program. Participants underwent a graded exercise test on a cycle ergometer with breath by breath open circuit spirometry after which they wore a wrist worn accelerometer (Actigraph) for 7 d. Absolute and relative submaximal and maximal OUES were calculated by plotting V̇O2 in mL/min on the x axis, and the log transformed VE on the y axis (V̇O2 = a log 10 VE + b). Exercise data up to the ventilatory anaerobic threshold and maximal exercise were used to calculate submaximal and maximal OUE, respectively. Results: Participants performed 584.49 73.87 min of daily LIPA, 145.45 60.85 min of MIPA and no daily min of VIPA. There was a significant relation between absolute submaximal OUES (r=0.386; p<0.01), submaximal OUES/Kg (r=0.296; p<0.05) and LIPA. There was a significant relation between maximal OUES (r=0.286; p<0.05), maximal OUES/Kg (r=0.279; p<0.05) and MIPA. Conclusion: Submaximal and maximal OUE are related to levels of LIPA and MIPA, respectively. Submaximal OUES can potentially be used as an objective, effort independent test to estimate LIPA levels among men with CVD

Physical activity patterns and cardiorespiratory fitness in men with cardiovascular disease

Purpose: Cardiorespiratory fitness (CRF) is generally regarded as an objective and reproducible measure of recent habitual physical activity (PA). Considering that the majority of daily PA is performed at light intensity, it is likely that CRF benefits will be detected at submaximal rather than maximal exercise. The purpose of this study was to evaluate daily minutes of light (LIPA), moderate (MIPA) and vigorous (VIPA) intensity physical activity among men with cardiovascular disease (CVD), and to determine the relation between PA and submaximal (oxygen uptake efficiency slope (OUES)) and maximal (V̇O2 peak) indices of CRF. Methods: A total 32 male participants (mean ( SD): age of 60.0 ± 8.7 yr, V̇O2 peak (L/min) 2.0 0.45, V̇O2 peak (mL/kg/min) 23.3 5.7, were recruited during an induction to a community based exercise referral program following completion of phase 2 cardiac rehabilitation. Participants underwent a graded exercise test on a cycle ergometer with breath by breath open circuit spirometry after which they wore a wrist worn accelerometer (Actigraph) for 7 d. Absolute and relative submaximal OUES were calculated by plotting V̇O2 in mL/min on the x axis, and the log transformed VE on the y axis (V̇O2 = a log 10 VE + b). Exercise data up to the ventilatory anaerobic threshold was included in the analysis. Results: Participants performed 589.05 69.41 min of daily LIPA, 161.38 66.16 min of MIPA and no daily min of VIPA. There was no significant relation between peak V̇O2 and either LIPA or MIPA. There was a significant correlation between submaximal OUES (r=0.44; p<0.01) and LIPA. The relation between submaximal OUES/kg and LIPA min almost reached statistical significance (r=0.33; p<0.07). There was no significant relation between MIPA and OUES or OUES/kg. Conclusion: Men with CVD spend the majority (78%) of their day performing LIPA. OUES, a submaximal measure of CRF was related LIPA whereas no relation was found between V̇O2 peak and LIPA