372 research outputs found

    Making sense of a mess: “doing” resilience in the vortex of a crisis

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    Purpose The purpose of the paper is to investigate how human resource professionals (HRPs), in a variety of organizations, responded to the crisis brought about by the event of COVID-19. In particular, it aims to show how organizations, across all sectors, in Western Australia responded with urgency and flexibility to the crisis and showed “resilience in practice”. Design/methodology/approach The study is based on 136 questionnaire responses, 32 interviews and 25 managerial narratives. The mixed qualitative methodology was designed to enable an investigation of the impact of COVID-19 and the response of HRPs. Findings HRPs have responded with agility and flexibility to the impact of COVID-19. They have done so through extensive trial and error, sometimes succeeding, sometimes failing. They have not simply activated a preconceived continuity plan. Research limitations/implications The research indicates that resilience is an ongoing accomplishment of organizations and the people in them. The objective was description rather than prescription, and the research does not offer solutions to future pandemic-like situations. Practical implications The research suggests that, given the impact of COVID-19 on organizations, HR practices, processes and policies will need to be thoroughly reconsidered for relevance in the post-COVID world. Possible future directions are highlighted. Originality/value The research considers the actions of HRPs as they responded to a global crisis as the crisis unfolded

    Mature T Cells Depend on Signaling through the IKK Complex

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    AbstractThe transcription factor NF-κB is implicated in various aspects of T cell development and function. The IκB kinase (IKK) complex, consisting of two kinases, IKK1/α and IKK2/β, and the NEMO/IKKγ regulatory subunit, mediates NF-κB activation by most known stimuli. Adoptive transfer experiments had demonstrated that IKK1 and IKK2 are dispensable for T cell development. We show here that T lineage-specific deletion of IKK2 allows survival of naive peripheral T cells but interferes with the generation of regulatory and memory T cells. T cell-specific ablation of NEMO or replacement of IKK2 with a kinase-dead mutant prevent development of peripheral T cells altogether. Thus, IKK-induced NF-κB activation, mediated by either IKK1 or IKK2, is essential for the generation and survival of mature T cells, and IKK2 has an additional role in regulatory and memory T cell development

    The impact of Covid-19 on human resource management: avoiding generalisations

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    Many organisations are using remote working for the first time. HR professionals are having to improvise daily, write Eileen Aitken-Fox, Jane Coffey, Kantha Dayaram, Scott Fitzgerald, Chahat Gupta, Steve McKenna, and Amy Wei Tia

    TRPC4 and GIRK channels underlie neuronal coding of firing patterns that reflect Gq/11-Gi/o coincidence signals of variable strengths

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    Transient receptor potential canonical 4 (TRPC4) is a receptor-operated cation channel codependent on both the Gq/11-phospholipase C signaling pathway and Gi/o proteins for activation. This makes TRPC4 an excellent coincidence sensor of neurotransmission through Gq/11- and Gi/o-coupled receptors. In whole-cell slice recordings of lateral septal neurons, TRPC4 mediates a strong depolarizing plateau that shuts down action potential firing, which may or may not be followed by a hyperpolarization that extends the firing pause to varying durations depending on the strength of Gi/o stimulation. We show that the depolarizing plateau is codependent on Gq/11-coupled group I metabotropic glutamate receptors and on Gi/o-coupled γ-aminobutyric acid type B receptors. The hyperpolarization is mediated by Gi/o activation of G protein-activated inwardly rectifying K+ (GIRK) channels. Moreover, the firing patterns, elicited by either electrical stimulation or receptor agonists, encode information about the relative strengths of Gq/11 and Gi/o inputs in the following fashion. Pure Gq/11 input produces weak depolarization accompanied by firing acceleration, whereas pure Gi/o input causes hyperpolarization that pauses firing. Although coincident Gq/11-Gi/o inputs also pause firing, the pause is preceded by a burst, and both the pause duration and firing recovery patterns reflect the relative strengths of Gq/11 versus Gi/o inputs. Computer simulations demonstrate that different combinations of TRPC4 and GIRK conductances are sufficient to produce the range of firing patterns observed experimentally. Thus, concurrent neurotransmission through the Gq/11 and Gi/o pathways is converted to discernible electrical responses by the joint actions of TRPC4 and GIRK for communication to downstream neurons.Fil: Tian, Jin Bin. University of Texas; Estados UnidosFil: Yang, Jane. University Of Toronto. Hospital For Sick Children; CanadáFil: Joslin, William C.. University of Texas; Estados UnidosFil: Flockerzi, Veit. Universitat Saarland; AlemaniaFil: Prescott, Steven A.. University Of Toronto. Hospital For Sick Children; CanadáFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Zhu, Michael X.. University of Texas; Estados Unido

    Air temperature equation derived from sonic temperature and water vapor mixing ratio for air flow sampled through closed-path eddy-covariance flux systems

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    Air temperar (T) plays a fundamental role in many aspects of the flux exchanges between the atmosphere and ecosystems. Additionally, it is critical to know where (in relation to other essential measurements) and at what frequency T must be measured to accurately describe such exchanges. In closed-path eddy-covariance (CPEC) flux systems, T can be computed from the sonic temperature (Ts) and water vapor mixing ratio that are measured by the fast-response senosrs of three-dimensional sonic anemometer and infrared gas analyzer, respectively. T then is computed by use of either T = Ts( 1+0.51 q), where q is specific humidity, or T = Ts( 1 + 0.32e∕ P) − 1 , where e is water vapor pressure and P is atmospheric pressure. Converting q and e/P into the same water vapor mixing ratio analytically reveals the difference between these two equations. This difference in a CPEC system could reach ±0.18 K, bringing an uncertainty into the accuracy of T from both equations and raises the question of which equation is better. To clarify the uncertainty and to answer this question, the derivation of T equations in terms of Ts and H2O-related variables is thoroughly studied. The two equations above were developed with approximations. Therefore, neither of their accuracies were evaluated, nor was the question answered. Based on the first principles, this study derives the T equation in terms of Ts and water vapor molar mixing ratio (c H2O) without any assumption and approximation. Thus, this equation itself does not have any error and the accuracy in T from this equation (equation-computed T) depends solely on the measurement accuracies of Ts and c H2O . Based on current specifications for Ts and c H2O in the CPEC300 series and given their maximized measurement uncertainties, the accuracy in equation-computed T is specified within ±1.01 K. This accuracy uncertainty is propagated mainly (±1.00K) from the uncertainty in Ts measurements and little (±0.03K) from the uncertainty in c H2O measurements. Apparently, the improvement on measurement technologies particularly for Ts would be a key to narrow this accuracy range. Under normal sensor and weather conditions, the specified accuracy is overestimated and actual accuracy is better. Equation-computed T has frequency response equivalent to high-frequency Ts and is insensitive to solar contamination during measurements. As synchronized at a temporal scale of measurement frequency and matched at a spatial scale of measurement volume with all aerodynamic and thermodynamic variables, this T has its advanced merits in boundary-layer meteorology and applied meteorology

    CC Chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo

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    El copyright pertenece a The Rockefeller University PressIsolated peripheral blood CD4 cells from allergic individuals express CC chemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, human T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond preferentially to the ligands eotaxin and monocyte-derived chemokine (MDC). However, controversy arises when the in vivo significance of this distinct expression is discussed. To address the functional role of CCR3/eotaxin and CCR4/MDC during the in vivo recruitment of Th2 cells, we have transferred effector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both CCR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these receptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin pathway is confined to early stages of the response in vivo, whereas repeated antigen stimulation results in the predominant use of the CCR4/MDC pathway. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4/MDC pathways initially, but that a progressive increase in CCR4-positive cells results in the predomipredominance of the CCR4/MDC axis in the long-term recruitment of Th2 cells in vivo.Peer reviewe

    Effects of AgRP Inhibition on Energy Balance and Metabolism in Rodent Models

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    Activation of brain melanocortin-4 receptors (MC4-R) by α-melanocyte-stimulating hormone (MSH) or inhibition by agouti-related protein (AgRP) regulates food intake and energy expenditure and can modulate neuroendocrine responses to changes in energy balance. To examine the effects of AgRP inhibition on energy balance, a small molecule, non-peptide compound, TTP2515, developed by TransTech Pharma, Inc., was studied in vitro and in rodent models in vivo. TTP2515 prevented AgRP from antagonizing α-MSH-induced increases in cAMP in HEK 293 cells overexpressing the human MC4-R. When administered to rats by oral gavage TTP2515 blocked icv AgRP-induced increases in food intake, weight gain and adiposity and suppression of T4 levels. In both diet-induced obese (DIO) and leptin-deficient mice, TTP2515 decreased food intake, weight gain, adiposity and respiratory quotient. TTP2515 potently suppressed food intake and weight gain in lean mice immediately after initiation of a high fat diet (HFD) but had no effect on these parameters in lean chow-fed mice. However, when tested in AgRP KO mice, TTP2515 also suppressed food intake and weight gain during HFD feeding. In several studies TTP2515 increased T4 but not T3 levels, however this was also observed in AgRP KO mice. TTP2515 also attenuated refeeding and weight gain after fasting, an effect not evident in AgRP KO mice when administered at moderate doses. This study shows that TTP2515 exerts many effects consistent with AgRP inhibition however experiments in AgRP KO mice indicate some off-target effects of this drug. TTP2515 was particularly effective during fasting and in mice with leptin deficiency, conditions in which AgRP is elevated, as well as during acute and chronic HFD feeding. Thus the usefulness of this drug in treating obesity deserves further exploration, to define the AgRP dependent and independent mechanisms by which TTP2515 exerts its effects on energy balance
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