The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration

Matrilins are adaptor proteins of the extracellular matrix involved in the formation of both collagen-dependent and collagen-independent filamentous networks. Although their molecular structure and binding partners have been characterized, the functional roles of the four matrilin family members in vivo are still largely unknown. Here, we show that matrilin 2, expressed in pre-myelinating Schwann cells during normal development, profoundly influences the behaviour of glial cells and neurons in vitro. When offered as a uniform substrate, matrilin 2 increased neurite outgrowth of dorsal root ganglia (DRG) neurons and enhanced the migration of both cell line- and embryonic DRG-derived Schwann cells. Vice versa, axonal outgrowth and cell migration were decreased in DRG cultures prepared from matrilin-2-deficient mice compared with wild-type (wt) cultures. In stripe assays, matrilin 2 alone was sufficient to guide axonal growth and, interestingly, axons favoured the combination of matrilin 2 and laminin over laminin alone. In vivo, matrilin 2 was strongly upregulated in injured peripheral nerves of adult wild-type mice and failure of protein upregulation in knockout mice resulted in delayed regrowth of regenerating axons and delayed time-course of functional recovery. Strikingly, the functional recovery 2 months after nerve injury was inferior in matrilin-2-deficient mice compared with wild-type littermates, although motoneuron survival, quality of axonal regeneration, estimated by analyses of axonal diameters and degrees of myelination, and Schwann cell proliferation were not influenced by the mutation. These results show that matrilin 2 is a permissive substrate for axonal growth and cell migration, and that it is required for successful nerve regeneratio

Update in the methodology of the chronic stress paradigm: internal control matters

To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals

Long-term monitoring of landfast sea ice extent and thickness in Kongsfjorden, and related applications (FastIce)

Landfast sea ice covers the inner parts of Kongsfjorden, Svalbard, for a limited time in winter and spring months, being an important feature for the physical and biological fjord systems. Systematic fast-ice monitoring for Kongsfjorden, as a part of a long-term project at the Norwegian Polar Institute (NPI) was started in 2003, with some more sporadic observations from 1997 to 2002. It includes the ice extent mapping and in situ measurements of ice and snow thickness, and freeboard at several sites in the fjord. The permanent presence of NPI personnel in Ny-Ålesund Research Station enables regular in situ fast-ice thickness measurements as long as the fast ice is accessible. Further, daily visits to the observatory on the mountain Zeppelinfjellet close to Ny-Ålesund, allow regular ice extent observations (weather, visibility, and daylight permitting). Data collected within this standardized monitoring programme have contributed to a number of studies. Monitoring of the sea-ice conditions in Kongsfjorden can be used to demonstrate and investigate phenomena related to climate change in the Arctic

Astrocytes promote progression of breast cancer metastases to the brain via a KISS1-mediated autophagy.

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level via induction of microRNA-345 (MIR345). Furthermore, we demonstrated that ectopic expression of KISS1 downregulates ATG5 and ATG7, 2 key modulators of autophagy, and works concurrently with autophagy inhibitors, thereby implicating autophagy in the mechanism of KISS1-mediated BrCa metastatic transformation. We also found that expression of KISS1 in human breast tumor specimens inversely correlates with that of MMP9 and IL8, implicated in the mechanism of metastatic invasion, thereby supporting the role of KISS1 as a potential regulator of BrCa metastatic invasion in the brain. This conclusion is further supported by the ability of KISS1, ectopically overexpressed from an adenoviral vector in MDA-MB-231Br cells with silenced expression of the endogenous gene, to revert invasive phenotype of those cells. Taken together, our results strongly suggest that human adult astrocytes can promote brain invasion of the brain-localized circulating breast cancer cells by upregulating autophagy signaling pathways via the CXCL12-MIR345- KISS1 axis

The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2.

BACKGROUND: A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. RESULTS: Administration of DS (25 mg/kg/day, intraperitoneal) in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. CONCLUSIONS: Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.journal articleresearch support, non-u.s. gov't2012 Sep 182012 09 18importe

A dataset of direct observations of sea ice drift and waves in ice

Variability in sea ice conditions, combined with strong couplings to the atmosphere and the ocean, lead to a broad range of complex sea ice dynamics. More in-situ measurements are needed to better identify the phenomena and mechanisms that govern sea ice growth, drift, and breakup. To this end, we have gathered a dataset of in-situ observations of sea ice drift and waves in ice. A total of 15 deployments were performed over a period of 5 years in both the Arctic and Antarctic, involving 72 instruments. These provide both GPS drift tracks, and measurements of waves in ice. The data can, in turn, be used for tuning sea ice drift models, investigating waves damping by sea ice, and helping calibrate other sea ice measurement techniques, such as satellite based observations

An International Study on Psychological Coping During COVID-19: Towards a Meaning-Centered Coping Style

Background/Objective This study examined the role of different psychological coping mechanisms in mental and physical health during the initial phases of the COVID-19 crisis with an emphasis on meaning-centered coping. Method A total of 11,227 people from 30 countries across all continents participated in the study and completed measures of psychological distress (depression, stress, and anxiety), loneliness, well-being, and physical health, together with measures of problem-focused and emotion-focused coping, and a measure called the Meaning-centered Coping Scale (MCCS) that was developed in the present study. Validation analyses of the MCCS were performed in all countries, and data were assessed by multilevel modeling (MLM). Results The MCCS showed a robust one-factor structure in 30 countries with good test-retest, concurrent and divergent validity results. MLM analyses showed mixed results regarding emotion and problem-focused coping strategies. However, the MCCS was the strongest positive predictor of physical and mental health among all coping strategies, independently of demographic characteristics and country-level variables. Conclusions The findings suggest that the MCCS is a valid measure to assess meaning-centered coping. The results also call for policies promoting effective coping to mitigate collective suffering during the pandemic

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Newly-formed sea ice distinction near the oil platform Prirazlomnaya in the Pechora Sea using polarimetric Radarsat-2 SAR observations

Source at https://www.vde-verlag.de/proceedings-de/455457112.html.A polarimetric approach developed to discriminate oil slicks and look-alikes was used to study the polarimetric properties of newly-formed ice (NFI) observed near the Prirazlomnaya oil platform. This approach is based on the multipolarization parameter called Resonant to Non-resonant signal Damping (RND), which is related to the ratio between the ice damping and the short wind waves and wave breakings. Fully-polarimetric Radarsat-2 images containing NFI were analyzed. The RND parameter indicates that in many cases the damping of the resonant and non-resonant electromagnetic signals in NFI is significantly different from oil slicks and that the RND parameter can distinguish them