Learning in an Agile Setting: A Multilevel Study on the Evolution of Organizational Routines

Recognizing a serious lack of research on routinized individual actions and organizational adaptation in the stability-change paradox, we intend to provide an in-depth explanation of the way in which agile methods affect organizational learning in self-managed, team-based organizations, taking a multi-level evolutionary approach. We explore learning in agile organizations by breaking the analysis of organizational routines down into different levels \u2013 individual, team and organization \u2013 and describing the process of variation, selection and retention of routines at each level. Leveraging on multiple case studies, we discuss how team members learn and gain knowledge, from both direct and indirect experience, and analyze how teams develop conceptual frameworks and interpret those experiences. Finally, we discuss how organizational memory develops and how teams in agile organizations adapt simultaneously within an ecological structure that also comprises the changing environment. Our findings reveal substantial flaws in the capacity of agile methods to foster organizational learning

Yamanaka Factors in the Budding Tunicate Botryllus schlosseri Show a Shared Spatio-Temporal Expression Pattern in Chordates

In vertebrates, the four transcription factors Sox2, c-Myc, Pou5f1 and Klf4 are involved in the differentiation of several tissues during vertebrate embryogenesis; moreover, they are normally co-expressed in embryonic stem cells and play roles in pluripotency, self-renewal, and maintenance of the undifferentiated state in adult cells. The in vitro forced co-expression of these factors, named Yamanaka factors (YFs), induces pluripotency in human or mouse fibroblasts. Botryllus schlosseri is a colonial tunicate undergoing continuous stem cell-mediated asexual development, providing a valuable model system for the study of pluripotency in the closest living relatives of vertebrates. In this study, we identified B. schlosseri orthologs of human Sox2 and c-Myc genes, as well as the closest homologs of the vertebrate-specific Pou5f1 gene, through an in-depth evolutionary analysis of the YF gene families in tunicates and other deuterostomes. Then, we studied the expression of these genes during the asexual cycle of B. schlosseri using in situ hybridization in order to investigate their possible involvement in tissue differentiation and in pluripotency maintenance. Our results show a shared spatio-temporal expression pattern consistent with the reported functions of these genes in invertebrate and vertebrate embryogenesis. Moreover, Myc, SoxB1 and Pou3 were expressed in candidate stem cells residing in their niches, while Pou2 was found expressed exclusively in the immature previtellogenic oocytes, both in gonads and circulating in the colonial vascular system. Our data suggest that Myc, SoxB1 and Pou3 may be individually involved in the differentiation of the same territories seen in other chordates, and that, together, they may play a role in stemness even in this colonial ascidian

Granulocytic myeloid-derived suppressor cells increased in early phases of primary HIV infection depending on TRAIL plasma level

Background It has been demonstrated that Myeloid Derived Suppressor Cells (MDSC) are expanded in HIV-1 infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study we evaluated the frequency of MDSC in patients during primary HIV infection, and factors involved in MDSC control. Methods Patients with primary (PHI) and chronic (CHI) HIV infection were enrolled. PHI staging was performed according to Fiebig classification, and circulating MDSC frequency and function were evaluated by flow cytometry. Cytokine levels were evaluated by Luminex technology. Results We found that granulocytic MDSC (Gr-MDSC) frequency was higher in PHI compared to healthy donors, but lower than CHI. Interestingly, Gr-MDSC expansion was observed in the early phases of HIV infection (Fiebig II/III), but it was not associated to HIV viral load and CD4 T cell count. Interestingly, in PHI Gr-MDSC frequency was inversely correlated with plasmatic level of TRAIL, while a direct correlation was observed in CHI. Further, lower level of GMCSF was observed in PHI compared with CHI. In vitro experiments demonstrated that, differently from CHI, recombinant TRAIL induced apoptosis of Gr-MDSC from PHI, can effect that can be abrogated by GM-CSF. Conclusion We found that Gr-MDSC are expanded early during primary HIV infection and may be regulated by TRAIL and GM-CSF levels. These findings shed light on the fine mechanisms regulating the immune system during HIV infection, and open new perspectives for immune-based strategies

An integrated Italian research project on organic animal husbandry

In 2005, huge project of integrated re-search on organic animal husbandry was initiated in Italy. This research combines, for the first time in Italy, various disciplines in order to affront existing problems in the animal organic sector. The research will be conducted on 19 farms, located across South-ern, Central and Northern Italy, in order to fully rep-resent the climatic environments of the Italian penin-sula. The topics investigated range from a complete substitution of soy in animal feed to avoid GMOs, to the reduction of micotoxin contamination risks, to pasture improvement and to the use of animal breeds more adapted to organic production. The project duration will be 3 years, and is expected to provide Italian organic farm breeders the long-awaited an-swers to various questions

Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic hepatitis C virus infection

CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation (CIA). Here, we found that both apoptotic epitope (AE)-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper-1-like signature program in chronic (c)HCV infection. However, AE-specific CD8(+) T cells produced tumor necrosis factor (TNF)-α and interleukin-2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations acquiring high levels of programmed death-1 receptor expression. Contextually, only AE-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Taken together, these data suggest that AE-specific CD8(+) T cells can sustain CIA by their capacity to produce TNF-α and be resistant to inhibitory signals more than HCV-specific CD8(+) T cells in cHCV infection

Molecular epidemiology of Usher syndrome in Italy

Purpose: Usher syndrome is an autosomal recessive disorder characterized by hearing and vision loss. Usher syndrome is divided into three clinical subclasses (type 1, type 2, and type 3), which differ in terms of the severity and progression of hearing loss and the presence or absence of vestibular symptoms. Usher syndrome is defined by significant genetic heterogeneity, with at least 12 distinct loci described and 9 genes identified. This study aims to provide a molecular epidemiology report of Usher syndrome in Italy. Methods: Molecular data have been obtained on 75 unrelated Italian patients using the most up-to date technology available for the screening of Usher syndrome gene mutations, i.e., the genotyping microarray developed by Asper Biotech (Tartu, Estonia), which simultaneously investigates 612 different marker positions using the well established arrayed primer extension methodology (APEX). Results: Using this method, we found that 12% of cases (9 out of 75) harbored homozygous or compound heterozygous mutations in the gene positions analyzed, whereas 20% (15 out of 75) of the patients were characterized by the presence of only one mutated allele based on the positions analyzed. One patient was found to be compound heterozygous for mutations in two different genes and this represents an example of possible digenic inheritance in Usher syndrome. A total of 66.6% of cases (50 out of 75) were found to be completely negative for the presence of Usher syndrome gene mutations in the detected positions. Mutations detected by the array were confirmed by direct sequencing. Conclusions: These findings highlight the efficacy of the APEX-based genotyping approach in the molecular assessment of Usher patients, suggesting the presence of alleles not yet identified and/or the involvement of additional putative genes that may account for the pathogenesis of Usher syndrome

New Indole Tubulin Assembly Inhibitors Cause Stable Arrest of Mitotic Progression, Enhanced Stimulation of Natural Killer Cell Cytotoxic Activity, and Repression of Hedgehog-Dependent Cancer

We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression. Cell cycle arrest was followed by cell death. Indoles 33, 44, and 81 showed strong inhibition of the SAG-induced Hedgehog signaling activation in NIH3T3 Shh-Light II cells with IC50 values of 19, 72, and 38 nM, respectively. Compounds of this class potently inhibited tubulin polymerization and cancer cell growth, including stimulation of natural killer cell cytotoxic activity and repression of Hedgehog-dependent cancer

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management