Experimental and Theoretical Analysis of Non-linear Vibrational Relaxation of Polyatomic Molecules Strongly Excited by Resonant Laser Radiation

We present a very simple theoretical model aimed at the analysis of non-linear relaxation processes in molecular gases in the presence of partial molecular dissociation induced by vibrational–vibrational exchange between highly excited molecules. The model has a phenomenological character, since it analyzes the behavior of a system of anharmonic diatomic molecules, which is a very rough approximation of a polyatomic molecule such as SF6. Nonetheless, it provides an interesting key for the interpretation of a number of peculiar features characterizing our experimental observation, with which a comparison is made. In particular, the model takes realistic account of the influence of dissociation processes on the relaxation time

The imbalance between dynamic and stable microtubules underlies neurodegeneration induced by 2,5-hexanedione

Exposure to environmental toxins, including hydrocarbon solvents, increases the risk of developing Parkinson's disease. An emergent hypothesis considers microtubule dysfunction as one of the crucial events in triggering neuronal degeneration in Parkinson's disease. Here, we used 2,5-hexanedione (2,5-HD), the toxic metabolite of n-hexane, to analyse the early effects of toxin-induced neurodegeneration on the cytoskeleton in multiple model systems. In PC12 cells differentiated with nerve growth factor for 5 days, we found that 2,5-HD treatment affected all the cytoskeletal components. Moreover, we observed alterations in microtubule distribution and stability, in addition to the imbalance of post-translational modifications of \u3b1-tubulin. Similar defects were also found in vivo in 2,5-HD-intoxicated mice. Interestingly, we also found that 2,5-HD exposure induced significant changes in microtubule stability in human skin fibroblasts obtained from Parkinson's disease patients harbouring mutations in PRKN gene, whereas it was ineffective in healthy donor fibroblasts, suggesting that the genetic background may really make the difference in microtubule susceptibility to this environmental Parkinson's disease-related toxin. In conclusion, by showing the imbalance between dynamic and stable microtubules in hydrocarbon-induced parkinsonism, our data support the crucial role of microtubule defects in triggering neurodegeneration

Conceptual Challenges for Advancing the Socio-Technical Underpinnings of Health Informatics

This discussion paper considers the adoption of socio-technical perspectives and their theoretical and practical influence within the discipline of health informatics. The paper highlights the paucity of discussion of the philosophy, theory and concepts of socio-technical perspectives within health informatics. Instead of a solid theoretical base from which to describe, study and understand human-information technology interactions we continue to have fragmented, unelaborated understandings. This has resulted in a continuing focus on technical system performance and increasingly managerial outputs to the detriment of social and technical systems analysis. It has also limited critical analyses and the adaptation of socio-technical approaches beyond the immediate environment to the broader social systems of contemporary society, an expansion which is increasingly mandated in today’s complex health environment

Status of low-energy accelerator-based BNCT worldwide and in Argentina

Existing and active low-energy Accelerator-Based BNCT programs worldwide will be reviewed and compared. In particular, the program in Argentina will be discussed which consists of the development of an Electro-Static-Quadrupole (ESQ) Accelerator-Based treatment facility. The facility is conceived to operate with the deuteron-induced reactions 9Be(d,n)10B and 13C(d,n)14N at 1.45 MeV deuteron energy, as neutron sources. Neutron production target development status is specified. The present status of the construction of the new accelerator development laboratory and future BNCT centre is shown.Fil: Cartelli, Daniel Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Capoulat, Maria Eugenia. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baldo, M.. Comisión Nacional de Energía Atómica; ArgentinaFil: Suárez Sandín, J. C.. Comisión Nacional de Energía Atómica; ArgentinaFil: Igarzabal, M.. Comisión Nacional de Energía Atómica; ArgentinaFil: del Grosso, Mariela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Valda, A. A.. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Canepa, N.. Comisión Nacional de Energía Atómica; ArgentinaFil: Gun, M.. Comisión Nacional de Energía Atómica; ArgentinaFil: Minsky, Daniel Mauricio. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Conti, G.. Comisión Nacional de Energía Atómica; ArgentinaFil: Erhardt, J.. Comisión Nacional de Energía Atómica; ArgentinaFil: Somacal, Héctor Rubén. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Bertolo, A. A.. Comisión Nacional de Energía Atómica; ArgentinaFil: Bergueiro, J.. Comisión Nacional de Energía Atómica; ArgentinaFil: Gaviola, P. A.. Comisión Nacional de Energía Atómica; ArgentinaFil: Kreiner, Andres Juan. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Effects of Bariatric Surgery on COVID-19: a Multicentric Study from a High Incidence Area

Introduction: The favorable effects of bariatric surgery (BS) on overall pulmonary function and obesity-related comorbidities could influence SARS-CoV-2 clinical expression. This has been investigated comparing COVID-19 incidence and clinical course between a cohort of patients submitted to BS and a cohort of candidates for BS during the spring outbreak in Italy. Materials and Methods: From April to August 2020, 594 patients from 6 major bariatric centers in Emilia-Romagna were administered an 87-item telephonic questionnaire. Demographics, COVID-19 incidence, suggestive symptoms, and clinical outcome parameters of operated patients and candidates to BS were compared. The incidence of symptomatic COVID-19 was assessed including the clinical definition of probable case, according to World Health Organization criteria. Results: Three hundred fifty-three operated patients (Op) and 169 candidates for BS (C) were finally included in the statistical analysis. While COVID-19 incidence confirmed by laboratory tests was similar in the two groups (5.7% vs 5.9%), lower incidence of most of COVID-19-related symptoms, such as anosmia (p: 0.046), dysgeusia (p: 0.049), fever with rapid onset (p: 0.046) were recorded among Op patients, resulting in a lower rate of probable cases (14.4% vs 23.7%; p: 0.009). Hospitalization was more frequent in C patients (2.4% vs 0.3%, p: 0.02). One death in each group was reported (0.3% vs 0.6%). Previous pneumonia and malignancies resulted to be associated with symptomatic COVID-19 at univariate and multivariate analysis. Conclusion: Patients submitted to BS seem to develop less severe SARS-CoV-2 infection than subjects suffering from obesity

Microtubule alterations occur early in experimental Parkinsonism and the microtubule stabilizer epothilone D is neuroprotective

The role of microtubule (MT) dysfunction in Parkinson\u2019s disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl mice. MPTP induced a time- and dose-dependent increase in fibres with altered mitochondria distribution, and early changes in cytoskeletal proteins and MT stability. Indeed, we observed significant increases in neuron-specific betaIII tubulin and enrichment of deTyr tubulin in dopaminergic neurons. Finally, we showed that repeated daily administrations of the MT stabilizer Epothilone D rescued MT defects and attenuated nigrostriatal degeneration induced by MPTP. These data suggest that alteration of MTs is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism

Nerve growth factor induces neurite outgrowth of PC12 cells by promoting Gβγ-microtubule interaction

Background: Assembly and disassembly of microtubules (MTs) is critical for neurite outgrowth and differentiation. Evidence suggests that nerve growth factor (NGF) induces neurite outgrowth from PC12 cells by activating the receptor tyrosine kinase, TrkA. G protein-coupled receptors (GPCRs) as well as heterotrimeric G proteins are also involved in regulating neurite outgrowth. However, the possible connection between these pathways and how they might ultimately converge to regulate the assembly and organization of MTs during neurite outgrowth is not well understood. Results: Here, we report that Gβγ, an important component of the GPCR pathway, is critical for NGF-induced neuronal differentiation of PC12 cells. We have found that NGF promoted the interaction of Gβγ with MTs and stimulated MT assembly. While Gβγ-sequestering peptide GRK2i inhibited neurite formation, disrupted MTs, and induced neurite damage, the Gβγ activator mSIRK stimulated neurite outgrowth, which indicates the involvement of Gβγ in this process. Because we have shown earlier that prenylation and subsequent methylation/demethylation of γ subunits are required for the Gβγ-MTs interaction in vitro, small-molecule inhibitors (L-28 and L-23) targeting prenylated methylated protein methyl esterase (PMPMEase) were tested in the current study. We found that these inhibitors disrupted Gβγ and ΜΤ organization and affected cellular morphology and neurite outgrowth. In further support of a role of Gβγ-MT interaction in neuronal differentiation, it was observed that overexpression of Gβγ in PC12 cells induced neurite outgrowth in the absence of added NGF. Moreover, overexpressed Gβγ exhibited a pattern of association with MTs similar to that observed in NGF-differentiated cells. Conclusions: Altogether, our results demonstrate that βγ subunit of heterotrimeric G proteins play a critical role in neurite outgrowth and differentiation by interacting with MTs and modulating MT rearrangement. Electronic supplementary material The online version of this article (doi:10.1186/s12868-014-0132-4) contains supplementary material, which is available to authorized users

Mesenchymal Stromal Cells Primed with Paclitaxel Provide a New Approach for Cancer Therapy

BACKGROUND: Mesenchymal stromal cells may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that exposure of mouse bone marrow derived stromal cells to Doxorubicin led them to acquire anti-proliferative potential towards co-cultured haematopoietic stem cells (HSCs). We thus hypothesized whether freshly isolated human bone marrow Mesenchymal stem cells (hMSCs) and mature murine stromal cells (SR4987 line) primed in vitro with anti-cancer drugs and then localized near cancer cells, could inhibit proliferation. METHODS AND PRINCIPAL FINDINGS: Paclitaxel (PTX) was used to prime culture of hMSCs and SR4987. Incorporation of PTX into hMSCs was studied by using FICT-labelled-PTX and analyzed by FACS and confocal microscopy. Release of PTX in culture medium by PTX primed hMSCs (hMSCsPTX) was investigated by HPLC. Culture of Endothelial cells (ECs) and aorta ring assay were used to test the anti-angiogenic activity of hMSCsPTX and PTX primed SR4987(SR4987PTX), while anti-tumor activity was tested in vitro on the proliferation of different tumor cell lines and in vivo by co-transplanting hMSCsPTX and SR4987PTX with cancer cells in mice. Nevertheless, despite a loss of cells due to chemo-induced apoptosis, both hMSCs and SR4987 were able to rapidly incorporate PTX and could slowly release PTX in the culture medium in a time dependent manner. PTX primed cells acquired a potent anti-tumor and anti-angiogenic activity in vitro that was dose dependent, and demonstrable by using their conditioned medium or by co-culture assay. Finally, hMSCsPTX and SR4987PTX co-injected with human cancer cells (DU145 and U87MG) and mouse melanoma cells (B16) in immunodeficient and in syngenic mice significantly delayed tumor takes and reduced tumor growth. CONCLUSIONS: These data demonstrate, for the first time, that without any genetic manipulation, mesenchymal stromal cells can uptake and subsequently slowly release PTX. This may lead to potential new tools to increase efficacy of cancer therapy

Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

​Leucine-rich repeat kinase 2 (​LRRK2) mutations are the most common genetic cause of Parkinson’s disease. ​LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules. Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson’s disease, but whether ​LRRK2 mutations affect this process to mediate pathogenesis is not known. Here we find that ​LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo. In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase ​αTAT1 prevents association of mutant ​LRRK2 with microtubules, and the deacetylase inhibitor ​trichostatin A (​TSA) restores axonal transport. In vivo knockdown of the deacetylases ​HDAC6 and ​Sirt2, or administration of ​TSA rescues both axonal transport and locomotor behavior. Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson’s disease