Chaperone-Mediated Autophagy Markers LAMP2A and HSPA8 in Advanced Non-Small Cell Lung Cancer after Neoadjuvant Therapy.

In recent years autophagy has attracted the attention of researchers from many medical fields, including cancer research, and certain anti-macroautophagy drugs in combination with cytotoxic or targeted therapies have entered clinical trials. In the present study, we focused on a less explored subtype of autophagy, i.e., chaperone-mediated autophagy (CMA), with the key proteins LAMP2A and HSPA8 (HSC70), and their immunohistochemical evaluation with previously extensively validated antibodies. We were interested in whether the marker expression is influenced by the antecedent therapy, and its correlation with survival on a cohort of patients with non-small cell lung cancer (NSCLC) after neoadjuvant therapy and matched primary resected tumors. In concordance with our previous study, we did not find any intratumoral heterogeneity, nor correlation between the two parameters, nor correlation between the markers and any included pathological parameters. Surprisingly, the expression of both markers was also independent to tumor response or administered neoadjuvant treatment. In the survival analysis, the results were only significant for LAMP2A, where higher levels were associated with longer 5-year overall survival and disease-free survival for the mixed group of adenocarcinomas and squamous cell carcinomas (p < 0.0001 and p = 0.0019 respectively) as well as the squamous cell carcinoma subgroup (p = 0.0001 and p = 0.0001 respectively). LAMP2A was also an independent prognostic marker in univariate and multivariate analysis

Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia

The p73 protein shares structural and functional similarities with the tumour-suppressor p53, but its role in neoplastic transformation is unknown. Alternative splicing leads to the expression of at least nine p73 C-terminal mRNA splice variants (α β γ δ ε ξ η ηl θ). In this survey, we analyse the expression of p73 by real-time quantitative RT-PCR, its known C-terminal variants with an RT-PCR-Southern tech nique and by Western blot in samples of 51 patients with B-CLL, normal B lymphocytes from eight individuals, and five haematopoetic cell lines. p73α protein expression positively correlated with higher risk B-CLL stages (P=0.046). Total p73 mRNA expression was higher (P= 0.01) and p73α protein more frequently detected (P=0.008) in B-CLL compared with normal CD19+—B-lymphocytes. p73 C-terminal mRNA variants were expressed both in B-CLL and in normal B-lymphocytes, but their expression was biased since the γ (P=0.041), the θ (P ≪ 0.001), and the η variant (P=0.033) prevailed in normal B-lymphocytes. In summary, we conclude that the accumulation of p73, the expression pattern of particular p73 variants and its link to progression may play a distinct role in the molecular pathology B-CL

Hands-on time during cardiopulmonary resuscitation is affected by the process of teambuilding: a prospective randomised simulator-based trial

BACKGROUND: Cardiac arrests are handled by teams rather than by individual health-care workers. Recent investigations demonstrate that adherence to CPR guidelines can be less than optimal, that deviations from treatment algorithms are associated with lower survival rates, and that deficits in performance are associated with shortcomings in the process of team-building. The aim of this study was to explore and quantify the effects of ad-hoc team-building on the adherence to the algorithms of CPR among two types of physicians that play an important role as first responders during CPR: general practitioners and hospital physicians. METHODS: To unmask team-building this prospective randomised study compared the performance of preformed teams, i.e. teams that had undergone their process of team-building prior to the onset of a cardiac arrest, with that of teams that had to form ad-hoc during the cardiac arrest. 50 teams consisting of three general practitioners each and 50 teams consisting of three hospital physicians each, were randomised to two different versions of a simulated witnessed cardiac arrest: the arrest occurred either in the presence of only one physician while the remaining two physicians were summoned to help ("ad-hoc"), or it occurred in the presence of all three physicians ("preformed"). All scenarios were videotaped and performance was analysed post-hoc by two independent observers. RESULTS: Compared to preformed teams, ad-hoc forming teams had less hands-on time during the first 180 seconds of the arrest (93 +/- 37 vs. 124 +/- 33 sec, P > 0.0001), delayed their first defibrillation (67 +/- 42 vs. 107 +/- 46 sec, P > 0.0001), and made less leadership statements (15 +/- 5 vs. 21 +/- 6, P > 0.0001). CONCLUSION: Hands-on time and time to defibrillation, two performance markers of CPR with a proven relevance for medical outcome, are negatively affected by shortcomings in the process of ad-hoc team-building and particularly deficits in leadership. Team-building has thus to be regarded as an additional task imposed on teams forming ad-hoc during CPR. All physicians should be aware that early structuring of the own team is a prerequisite for timely and effective execution of CPR

Emerging technologies revolutionise insect ecology and monitoring

Insects are the most diverse group of animals on Earth, but their small size and high diversity have always made them challenging to study. Recent technologi- cal advances have the potential to revolutionise insect ecology and monitoring. We describe the state of the art of four technologies (computer vision, acoustic monitoring, radar, and molecular methods), and assess their advantages, current limitations, and future potential. We discuss how these technologies can adhere to modern standards of data curation and transparency, their implications for citizen science, and their potential for integration among different monitoring programmes and technologies. We argue that they provide unprecedented possibilities for insect ecology and monitoring, but it will be important to foster international standards via collaborationpublishedVersio

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Towards a multisensor station for automated biodiversity monitoring

Rapid changes of the biosphere observed in recent years are caused by both small and large scale drivers, like shifts in temperature, transformations in land-use, or changes in the energy budget of systems. While the latter processes are easily quantifiable, documentation of the loss of biodiversity and community structure is more difficult. Changes in organismal abundance and diversity are barely documented. Censuses of species are usually fragmentary and inferred by often spatially, temporally and ecologically unsatisfactory simple species lists for individual study sites. Thus, detrimental global processes and their drivers often remain unrevealed. A major impediment to monitoring species diversity is the lack of human taxonomic expertise that is implicitly required for large-scale and fine-grained assessments. Another is the large amount of personnel and associated costs needed to cover large scales, or the inaccessibility of remote but nonetheless affected areas. To overcome these limitations we propose a network of Automated Multisensor stations for Monitoring of species Diversity (AMMODs) to pave the way for a new generation of biodiversity assessment centers. This network combines cutting-edge technologies with biodiversity informatics and expert systems that conserve expert knowledge. Each AMMOD station combines autonomous samplers for insects, pollen and spores, audio recorders for vocalizing animals, sensors for volatile organic compounds emitted by plants (pVOCs) and camera traps for mammals and small invertebrates. AMMODs are largely self-containing and have the ability to pre-process data (e.g. for noise filtering) prior to transmission to receiver stations for storage, integration and analyses. Installation on sites that are difficult to access require a sophisticated and challenging system design with optimum balance between power requirements, bandwidth for data transmission, required service, and operation under all environmental conditions for years. An important prerequisite for automated species identification are databases of DNA barcodes, animal sounds, for pVOCs, and images used as training data for automated species identification. AMMOD stations thus become a key component to advance the field of biodiversity monitoring for research and policy by delivering biodiversity data at an unprecedented spatial and temporal resolution. (C) 2022 Published by Elsevier GmbH on behalf of Gesellschaft fur Okologie

The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis

T cell development results in the generation of both mature αβ and γδ T cells. While αβ T cells predominate in secondary lymphoid organs, γδ T cells are more abundant in mucosal tissues. PU.1, an Ets family transcription factor, also identified as the spleen focus forming virus proviral integration site-1 (Sfpi1) is essential for early stages of T cell development, but is down regulated during the DN T-cell stage.In this study, we show that in mice specifically lacking PU.1 in T cells using an lck-Cre transgene with a conditional Sfpi1 allele (Sfpi1(lck-/-)) there are increased numbers of γδ T cells in spleen, thymus and in the intestine when compared to wild-type mice. The increase in γδ T cell numbers in PU.1-deficient mice is consistent in γδ T cell subsets identified by TCR variable regions. PU.1-deficient γδ T cells demonstrate greater proliferation in vivo and in vitro.The increase of γδ T cell numbers in Lck-Cre deleter strains, where deletion occurs after PU.1 expression is diminished, as well as the observation that PU.1-deficient γδ T cells have greater proliferative responses than wild type cells, suggests that PU.1 effects are not developmental but rather at the level of homeostasis. Thus, our data shows that PU.1 has a negative influence on γδ T cell expansion

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques

Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation

We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN