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

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

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

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

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

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

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

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

Folding pathway of an Ig domain is conserved on and off the ribosome.

Proteins that fold cotranslationally may do so in a restricted configurational space, due to the volume occupied by the ribosome. How does this environment, coupled with the close proximity of the ribosome, affect the folding pathway of a protein? Previous studies have shown that the cotranslational folding process for many proteins, including small, single domains, is directly affected by the ribosome. Here, we investigate the cotranslational folding of an all-β Ig domain, titin I27. Using an arrest peptide-based assay and structural studies by cryo-EM, we show that I27 folds in the mouth of the ribosome exit tunnel. Simulations that use a kinetic model for the force dependence of escape from arrest accurately predict the fraction of folded protein as a function of length. We used these simulations to probe the folding pathway on and off the ribosome. Our simulations-which also reproduce experiments on mutant forms of I27-show that I27 folds, while still sequestered in the mouth of the ribosome exit tunnel, by essentially the same pathway as free I27, with only subtle shifts of critical contacts from the C to the N terminus

On the cosmic evolution of AGN obscuration and the X-ray luminosity function: XMM-Newton and Chandra spectral analysis of the 31.3 deg2^2 Stripe 82X

We present X-ray spectral analysis of XMM and Chandra observations in the 31.3 deg$^2$ Stripe-82X (S82X) field. Of the 6181 X-ray sources in this field, we analyze a sample of 2937 active galactic nuclei (AGN) with solid redshifts and sufficient counts determined by simulations. Our results show a population with median values of spectral index $\Gamma=1.94_{-0.39}^{+0.31}$, column density log$\,N_{\mathrm{H}}/\mathrm{cm}^{-2}=20.7_{-0.5}^{+1.2}$ and intrinsic, de-absorbed, 2-10 keV luminosity log$\,L_{\mathrm{X}}/\mathrm{erg\,s}^{-1}=44.0_{-1.0}^{+0.7}$, in the redshift range 0-4. We derive the intrinsic fraction of AGN that are obscured ($22\leq\mathrm{log}\,N_{\mathrm{H}}/\mathrm{cm}^{-2}<24$), finding a significant increase in the obscured AGN fraction with redshift and a decline with increasing luminosity. The average obscured AGN fraction is $57\pm4\%$ for log$\,L_{\mathrm{X}}/\mathrm{erg\,s}^{-1}>43$. This work constrains the AGN obscuration and spectral shape of the still uncertain high-luminosity and high-redshift regimes (log$\,L_{\mathrm{X}}/\mathrm{erg\,s}^{-1}>45.5$, $z>3$), where the obscured AGN fraction rises to $64\pm12\%$. We report a luminosity and density evolution of the X-ray luminosity function, with obscured AGN dominating at all luminosities at $z>2$ and unobscured sources prevailing at log$\,L_{\mathrm{X}}/\mathrm{erg\,s}^{-1}>45$ at lower redshifts. Our results agree with evolutionary models in which the bulk of AGN activity is triggered by gas-rich environments and in a downsizing scenario. Also, the black hole accretion density (BHAD) is found to evolve similarly to the star formation rate density, confirming the co-evolution between AGN and host-galaxy, but suggesting different time scales in their growing history. The derived BHAD evolution shows that Compton-thick AGN contribute to the accretion history of AGN as much as all other AGN populations combined.Comment: 31 pages, 35 figures, Accepted for publication in Ap