The short form of the Workplace Affective Commitment Multidimensional Questionnaire (WACMQ-S): A bifactor-ESEM approach among healthcare professionals

Although it has long been recognized that employees' workplace affective commitment can be directed at a variety of foci, theory and research on this multifocal perspective remain underdeveloped, possibly due to the lack of a short, yet comprehensive measure. The purpose of the present study was to assess the psychometric properties of a newly developed short (24-item) version of the Workplace Affective Commitment Multidimensional Questionnaire (WACMQ-S), covering affective commitment directed at the organization, supervisor, coworkers, customers, tasks, profession, work, and career. Using two independent samples of English - (N = 676, including 648 females) and French - (N = 733, including 593 females) speaking healthcare professionals and the newly developed bifactor-ESEM framework, the present study supported the factor validity, composite reliability, test-retest reliability, linguistic invariance, and criterion-related validity (in relation to turnover intentions, in-role performance, and organizational citizenship behaviors) of the WACMQ-S ratings. The results also demonstrated the superiority of a bifactor-ESEM representation of WACMQ-S ratings, confirming the importance of taking into account employees' global levels of commitment to their work life. Finally, the results also proved to be fully generalizable to subsamples of hospital and community healthcare professionals, as well as of nurses and beneficiary attendants

HTLV-1 propels thymic human T cell development in “human immune system” Rag2-/- gamma c-/- Mice

Alteration of early haematopoietic development is thought to be responsible for the onset of immature leukemias and lymphomas. We have previously demonstrated that TaxHTLV-1 interferes with ß- selection, an important checkpoint of early thymopoiesis, indicating that human T-cell leukemia virus type 1 (HTLV-1) infection has the potential to perturb thymic human αβ T-cell development. To verify that inference and to clarify the impact of HTLV-1 infection on human T-cell development, we investigated the in vivo effects of HTLV-1 infection in a “Human Immune System” (HIS) Rag2-/-γc-/- mouse model. These mice were infected with HTLV-1, at a time when the three main subpopulations of human thymocytes have been detected. In all but two inoculated mice, the HTLV-1 provirus was found integrated in thymocytes; the proviral load increased with the length of the infection period. In the HTLV-1-infected mice we observed alterations in human T-cell development, the extent of which correlated with the proviral load. Thus, in the thymus of HTLV-1-infected HIS Rag2-/-γc-/- mice, mature single-positive (SP) CD4+ and CD8+ cells were most numerous, at the expense of immature and double-positive (DP) thymocytes. These SP cells also accumulated in the spleen. Human lymphocytes from thymus and spleen were activated, as shown by the expression of CD25: this activation was correlated with the presence of tax mRNA and with increased expression of NF-kB dependent genes such as bfl-1, an anti-apoptotic gene, in thymocytes. Finally, hepato-splenomegaly, lymphadenopathy and lymphoma/thymoma, in which Tax was detected, were observed in HTLV-1-infected mice, several months after HTLV-1 infection. These results demonstrate the potential of the HIS Rag2-/-γc-/- animal model to elucidate the initial steps of the leukemogenic process induced by HTLV-1

HTLV-1 clonality during chronic infection and BLV clonality during primary infection

peer reviewedaudience: researcherHTLV-1 clonality during chronic infection and BLV clonality during primary infection Nicolas A Gillet1,2*, Carol Hlela1, Tine Verdonck3, Eduardo Gotuzzo3, Daniel Clark3, Sabrina Rodriguez2, Nirav Malani4, Anat Melamed1, Niall Gormley5, Richard Carter5, David Bentley5, Charles Berry6, Frederic D Bushman4, Graham P Taylor7, Luc Willems2, Charles R M Bangham1 1Department of Immunology, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. 2Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liège (ULg), Liège, 4000, Belgium. 3Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. 4Department of Microbiology, University of Pennsylvania School of Medicine, Pennsylvania, Philadelphia, PA, 19104, USA. 5Illumina, Chesterford Research Park, Essex, Little Chesterford, CB10 1XL, UK. 6University of California, California, La Jolla San Diego, CA, 92093-0901, USA. 7Department of Genitourinary Medicine and Communicable Diseases, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. HTLV-1 persists by driving clonal proliferation of infected T-lymphocytes. A high proviral load predisposes to the inflammatory and malignant diseases associated with HTLV-1. Yet the reasons for the remarkable variation within and between individuals in the abundance of HTLV-1-infected clones remain unknown. We demonstrate that negative selection dominates during chronic infection, favouring establishment of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. We postulated that this selection occurred mainly during the primary infection. We are testing this hypothesis in an animal model by studying the BLV clonality during the primary infection in cows. By measuring the proviral load, the anti-BLV immune response and the BLV clonality we aim to quantify the impact of the immune response on the rate of infectious spread and on the selection of proviruses inserted in a particular genomic environment. Co-infection with Strongyloides stercoralis or Staphylococcus appears to be another risk factor for the development of HTLV-1 associated diseases. We observed that HTLV-1 clonality is altered by co-infection with these pathogens with an increase of both the number and the abundance of the infected T-cell clones. The genomic characteristics of the proviral integration sites in the most abundant clones differ significantly between co-infected individuals and those with HTLV-1 alone, implying the existence of different selection forces in co-infected patients. The rate of appearance of new clones in patients co-infected with Strongyloides stercoralis is higher than in patients with HTLV-1 alone. By comparing skin lesions and blood samples from patients with Infective Dermatitis associated with HTLV-1 (IDH), we observed a significant proportion of distinct infected clones between the two compartments. The skin lesions seem to be a site for HTLV-1 infectious spread

HTLV-1 propels thymic human T cell development in “human immune system” Rag2-/- IL-2R γc-/- Mice

Alteration of early haematopoietic development is thought to be responsible for the onset of immature leukemias and lymphomas. We have previously demonstrated that TaxHTLV-1 interferes with ß-selection, an important checkpoint of early thymopoiesis, indicating that human T-cell leukemia virus type 1 (HTLV-1) infection has the potential to perturb thymic human αβ T-cell development. To verify that inference and to clarify the impact of HTLV-1 infection on human T-cell development, we investigated the in vivo effects of HTLV-1 infection in a “Human Immune System” (HIS) Rag2-/-γc-/- mouse model. These mice were infected with HTLV-1, at a time when the three main subpopulations of human thymocytes have been detected. In all but two inoculated mice, the HTLV-1 provirus was found integrated in thymocytes; the proviral load increased with the length of the infection period. In the HTLV-1-infected mice we observed alterations in human T-cell development, the extent of which correlated with the proviral load. Thus, in the thymus of HTLV-1-infected HIS Rag2-/-γc-/- mice, mature single-positive (SP) CD4+ and CD8+ cells were most numerous, at the expense of immature and double-positive (DP) thymocytes. These SP cells also accumulated in the spleen. Human lymphocytes from thymus and spleen were activated, as shown by the expression of CD25: this activation was correlated with the presence of tax mRNA and with increased expression of NF-kB dependent genes such as bfl-1, an anti-apoptotic gene, in thymocytes. Finally, hepato-splenomegaly, lymphadenopathy and lymphoma/thymoma, in which Tax was detected, were observed in HTLV-1-infected mice, several months after HTLV-1 infection. These results demonstrate the potential of the HIS Rag2-/-γc-/- animal model to elucidate the initial steps of the leukemogenic process induced by HTLV-1

Whispering to the Deaf: Communication by a Frog without External Vocal Sac or Tympanum in Noisy Environments

Atelopus franciscus is a diurnal bufonid frog that lives in South-American tropical rain forests. As in many other frogs, males produce calls to defend their territories and attract females. However, this species is a so-called “earless” frog lacking an external tympanum and is thus anatomically deaf. Moreover, A. franciscus has no external vocal sac and lives in a sound constraining environment along river banks where it competes with other calling frogs. Despite these constraints, male A. franciscus reply acoustically to the calls of conspecifics in the field. To resolve this apparent paradox, we studied the vocal apparatus and middle-ear, analysed signal content of the calls, examined sound and signal content propagation in its natural habitat, and performed playback experiments. We show that A. franciscus males can produce only low intensity calls that propagate a short distance (<8 m) as a result of the lack of an external vocal sac. The species-specific coding of the signal is based on the pulse duration, providing a simple coding that is efficient as it allows discrimination from calls of sympatric frogs. Moreover, the signal is redundant and consequently adapted to noisy environments. As such a coding system can be efficient only at short-range, territory holders established themselves at short distances from each other. Finally, we show that the middle-ear of A. franciscus does not present any particular adaptations to compensate for the lack of an external tympanum, suggesting the existence of extra-tympanic pathways for sound propagation

PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1

The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that DDB2 facilitated poly(ADP-ribosyl)ation of UV-damaged chromatin through the activity of PARP1, resulting in the recruitment of the chromatin-remodeling enzyme ALC1. Depletion of ALC1 rendered cells sensitive to UV and impaired repair of UV-induced DNA lesions. Additionally, DDB2 itself was targeted by poly(ADP-ribosyl)ation, resulting in increased protein stability and a prolonged chromatin retention time. Our in vitro and in vivo data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of NER through DDB2 stabilization and recruitment of the chromatin remodeler ALC1