Segregated anatomical input to sub-regions of the rodent superior colliculus associated with approach and defense

The superior colliculus (SC) is responsible for sensorimotor transformations required to direct gaze toward or away from unexpected, biologically salient events. Significant changes in the external world are signaled to SC through primary multisensory afferents, spatially organized according to a retinotopic topography. For animals, where an unexpected event could indicate the presence of either predator or prey, early decisions to approach or avoid are particularly important. Rodents’ ecology dictates predators are most often detected initially as movements in upper visual field (mapped in medial SC), while appetitive stimuli are normally found in lower visual field (mapped in lateral SC). Our purpose was to exploit this functional segregation to reveal neural sites that can bias or modulate initial approach or avoidance responses. Small injections of Fluoro-Gold were made into medial or lateral sub-regions of intermediate and deep layers of SC (SCm/SCl). A remarkable segregation of input to these two functionally defined areas was found. (i) There were structures that projected only to SCm (e.g., specific cortical areas, lateral geniculate and suprageniculate thalamic nuclei, ventromedial and premammillary hypothalamic nuclei, and several brainstem areas) or SCl (e.g., primary somatosensory cortex representing upper body parts and vibrissae and parvicellular reticular nucleus in the brainstem). (ii) Other structures projected to both SCm and SCl but from topographically segregated populations of neurons (e.g., zona incerta and substantia nigra pars reticulata). (iii) There were a few brainstem areas in which retrogradely labeled neurons were spatially overlapping (e.g., pedunculopontine nucleus and locus coeruleus). These results indicate significantly more structures across the rat neuraxis are in a position to modulate defense responses evoked from SCm, and that neural mechanisms modulating SC-mediated defense or appetitive behavior are almost entirely segregated

THE IMPACT OF THE NEW ITALIAN EARLY WARNING SYSTEM PROVIDED BY THE IC-CODE ON FAMILY SMES GOVERNANCE

The Early Warning System is intended as an instrument aimed at driving the companies in the identification of the very first signs of crisis. Monitoring the occurring of the crisis is no longer a responsibility of the sole entrepreneur or of the board of directors but other legitimized subjects are identified. The IC-Code sets up new corporate governance rules for a huge number of Italian Family SMEs pretending the introduction of independent control bodies, Board of Statutory Auditors, and/or External Auditor. Some of the suggestions coming from the family business framework seems then to be enforced by law in the Italian context

Alloantigen-induced human lymphocytes rendered nonresponsive by a combination of anti-CD80 monoclonal antibodies and Cyclosporin-A suppress mixed lymphocyte reaction in vitro

Induction of a state of long-term, alloantigen-specific T cell nonresponsiveness has significant implications for human transplantation. It has been previously described that alloantigen-specific anergy may be induced by addition of cyclosporin-A together with anti-CD80(B7-1) mAb to a MLR. In this study we endeavored to verify whether alloantigen-induced PBL rendered anergic by the addition of a combination of anti-B7 mAb and cyclosporin-A during a MLR had a suppressive effect when added to autologous lymphocytes activated in MLR. We found that: 1) the addition of cells rendered anergic by this procedure to a MLR suppress both proliferative and cytotoxic response of autologous responsive PBL to either the same or third-party stimulator cells; 2) the suppressive effect is limited to alloantigen-induced T cell activation, as addition of anergic cells does not influence mitogen- or antigen-induced proliferation of autologous responsive T cells; 3) nonresponsiveness of suppressed cells cannot be reversed by either subsequent restimulation with allogeneic cells or addition of exogenous IL-2 to the cultures; 4) the suppressive effect is apparently not due to secretion of anergic cell-derived soluble factors, but it seems to be dependent on cell-cell contact between anergic, responsive, and stimulator cells. These data suggest that: 1) the delivery of a direct signal mediated by anergic lymphocytes through a cell-cell contact is likely to be the mechanism responsible for the suppressive effect here described; 2) anergic cells may propagate alloantigen-specific tolerance to potentially responsive autologous lymphocytes. Preliminary experiments indicate that anti-CD86(B7-2) mAb may play a similar role in the generation of alloantigen-induced nonresponsiveness

Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies

Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan–Meier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q−) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q−) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30–1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d−); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d−) years; HR 0.38; 95% CI 0.15–0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction

T Cell Therapy for Nasopharyngeal Carcinoma

Among the novel biologic therapeutics that will increase our ability to cure human cancer in the years to come, T cell therapy is one of the most promising approaches. However, with the possible exception of tumor-infiltrating lymphocytes therapy for melanoma, clinical trials of adoptive T-cell therapy for solid tumors have so far provided only clear proofs-of-principle to build on with further development. Epstein-Barr virus (EBV)-associated malignancies offer a unique model to develop T cell-based immune therapies, targeting viral antigens expressed on tumor cells. In the last two decades, EBV-specific cytotoxic T-lymphocytes (CTL) have been successfully employed for the prophylaxis and treatment of EBV-related lymphoproliferative disorders in immunocompromised hosts. More recently, this therapeutic approach has been applied to the setting of EBV-related solid tumors, such as nasopharyngeal carcinoma. The results are encouraging, although further improvements to the clinical protocols are clearly necessary to increase anti-tumor activity. Promising implementations are underway, including harnessing the therapeutic potential of CTLs specific for subdominant EBV latent cycle epitopes, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells

How Ethical Behavior Is Considered in Different Contexts: A Bibliometric Analysis of Global Research Trends

In the past, sustainable development was considered a guideline for all human activities, but the world has gradually changed. The criteria for action today must not only ensure sustainability but also meet appropriate ethical standards in diverse contexts. As a result, the topic of ethical behavior has been studied more extensively in recent studies. Accordingly, through bibliometric approaches, this study seeks to generalize the issues of ethical behavior explored in a variety of contexts from 1991 to 2022. A total of 1409 articles were found and extracted from the Web of Science using the keywords "ethical behavior" and "context"; they were then decoded using VOSviewer software (version 1.6). Three techniques, including bibliographic coupling, co-citation, and co-occurrence were conducted to identify the six most influential contexts in ethical behavior. The results demonstrate that the six most influential contexts in ethical behavior are consumption, leadership, business, organization, medical, and education. The results further revealed that leading countries such as the USA and UK have a larger number of studies on ethical behavior in many different contexts, such as organization, business, education, health, consumption, and politics. The Journal of Business Ethics leads the way in research into ethical behavior, followed by the Journal of Applied Psychology