The supporting role of the teres major muscle, an additional component in glenohumeral stability? An anatomical and radiological study

Muscle coordination plays an important role in glenohumeral stability. The rotator cuff and the long head of the biceps are considered the primary dynamic stabilizers muscles. However, the fact that a subgroup of patients with a massive tear in the rotator cuff were able to keep a normal function, should make us question this traditional view. We hypothesize that the teres major which is also a monoarticular scapulohumeral muscle, although it is not part of the conjoined tendon of the rotator cuff, can play a role in glenohumeral stability by a direct support of the humeral head generated by the particular posteroanterior location of this muscle under the humeral head and which, as far as we know, has not been written up previously. This particular effect could appear while the arm is being lifted and the humeral head could be leaning on against the teres major muscle belly underneath it. An anatomical a radiological study was carried out to substantiate our hypothesis. Two cadaver specimens were used for the anatomical study. Frist body was studied through conventional dissection. The second body was analysed through sectional anatomy. Then a radiological study was carried out using magnetic resonance imaging in a healthy male volunteer. Both anatomically and radiologically, the anteroinferior surface of the humeral head was showed firmly resting against the muscle belly of the teres major, to the point of misshaping it from 110 degrees of arm elevation with external rotation. The specific contribution of this effect to the glenohumeral stability needs to be confirmed by further studies and can help us to prevent the high incidence of glenohumeral dislocations

Frozen ground and snow cover monitoring in Livingston and Deception islands, Antarctica: preliminary results of the 2015-2019 PERMASNOW project

Since 2006, our research team has been establishing in the islands of Livingston and Deception, (South Shetland archipelago, Antarctica) several monitoring stations of the active layer thickness within the international network Circumpolar Active Layer Monitoring (CALM), and the ground thermal regime for the Ground Terrestrial Network-Permafrost (GTN-P). Both networks were developed within the International Permafrost Association (IPA). In the GTN-P stations, in addition to the temperature of the air, soil, and terrain at different depths, the snow thickness is also monitored by snow poles. Since 2006, a delay in the disappearance of the snow layer has been observed, which could explain the variations we observed in the active layer thickness and permafrost temperatures. Therefore, in late 2015 our research group started the PERMASNOW project (2015-2019) to pay attention to the effect of snow cover on ground thermal This project had two different ways to study the snow cover. On the first hand, in early 2017 we deployed new instrumentation, including new time lapse cameras, snow poles with high number of sensors and a complete and complex set of instruments and sensors to configure a snow pack analyzer station providing 32 environmental and snow parameters. We used the data acquired along 2017 and 2018 years with the new instruments, together with the available from all our already existing sensors, to study in detail the snow cover. On the other hand, remote sensing data were used to try to map the snow cover, not only at our monitoring stations but the entire islands in order to map and study the snow cover distribution, as well as to start the way for future permafrost mapping in the entire islands. MODIS-derived surface temperatures and albedo products were used to detect the snow cover and to test the surface temperature. Since cloud presence limited the acquisition of valid observations of MODIS sensor, we also analyzed Terrasar X data to overcome this limitation. Remote sensing data validation required the acquirement of in situ ground-true data, consisting on data from our permanent instruments, as well as ad hoc measurements in the field (snow cover mapping, snow pits, albedo characterization, etc.). Although the project is finished, the data analysis is still ongoing. We present here the different research tasks we are developing as well as the most important results we already obtained about the snow cover. These results confirm how the snow cover duration has been changing in the last years, affecting the ground thermal behavior.info:eu-repo/semantics/publishedVersio

Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles

A set of new pyrimido[5,4-b]indole derivatives that are structurally related to some non-nucleside HIV-1 reverse transcriptase inhibitors were synthesized and biologically evaluated for their activity as inhibitors of wild and mutant HIV-1 RT types in an 'in vitro' recombinant HIV-1 RT screening assay, as well as anti-infectives in HLT4lacZ-1IIIB cells. Preliminary structure-activity relationships suggest that activity is promoted by simultaneous substitution in positions 2 and 4, especially when chains of alkyldiamine type are present, and by electron-releasing substituents (methoxy) in positions 7 and 8. The inactivity or the very low activity of title derivatives does not suggest interest in AIDS therapy

Functional bold MRI: advantages of the 3 T vs. the 1.5 T

We quantitatively evaluate the benefits of a higher field strength for functional brain MRI (fMRI) based on the blood oxygenation level-dependent contrast. The 3-T fMRI shows a higher sensitivity for the motor and somatosensory stimulation and more specific localization in the grey substance. The 3-T fMRI detects additional areas of activation with the motor paradigm

Characterization of an immunologically conserved epitope from hepatitis C virus E2 glycoprotein recognized by HLA-A2 restricted cytotoxic T lymphocytes

BACKGROUND/AIMS: Identification of epitopes recognized by cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) proteins is of importance because they can be used for vaccination, treatment of infection or monitoring of immune responses. Our purpose was to characterize new CTL epitopes in HCV structural proteins. METHODS: Peptides were synthesized and tested in HLA-A2 binding assays. Binder peptides were used to stimulate peripheral blood mononuclear cells from HCV+ patients and controls, and activity measured in chromium release and ELISPOT assays. RESULTS: Twenty binder peptides were found, and stimulation of HCV+ patient cells with nine peptides showing high binding ability led to the growth of CD8+ CTL recognizing peptide E2(614-622) in association with HLA-A2. Peptide E2(614-622) was recognized by 30% of HLA-A2+ patients with chronic HCV infection, but no responses were observed in control groups. Five peptides derived from region E2(614-622) from 26 different viral isolates bound to HLA-A2 molecules, and all of them but one, containing Phe at position 622, were recognized by E2(614-622) specific CTL. CONCLUSIONS: These results show that peptide E2(614-622) belongs to a highly conserved region of HCV E2, and might be a good candidate to induce anti-HCV CTL responses in HLA-A2+ subjects

CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination

CD25(+) regulatory T (T reg) cells suppress the activation/proliferation of other CD4(+) or CD8(+) T cells in vitro. Also, down-regulation of CD25(+) T reg cells enhance antitumor immune responses. In this study, we show that depletion of CD25(+) T reg cells allows the host to induce both CD4(+) and CD8(+) antitumoral responses following tumor challenge. Simultaneous depletion of CD25(+) and CD8(+) cells, as well as adoptive transfer experiments, revealed that tumor-specific CD4(+) T cells, which emerged in the absence of CD25(+) T reg cells, were able to reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral effect mediated by CD4(+) T cells was dependent on IFN-gamma production, which exerted a potent antiangiogenic activity. The capacity of the host to mount this antitumor response is lost once the number of CD25(+) T reg cells is restored over time. However, CD25(+) T reg cell depletion before immunization with AH1 (a cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a long-lasting antitumoral immune response, not observed if immunization is conducted in the presence of regulatory cells. A study of the effect of different levels of depletion of CD25(+) T reg cells before immunization with the peptide AH1 alone, or in combination with a Th determinant, unraveled that Th cells play an important role in overcoming the suppressive effect of CD25(+) T reg on the induction of long-lasting cellular immune responses

Immunization with a tumor-associated CTL epitope plus a tumor-related or unrelated Th1 helper peptide elicits protective CTL immunity

Immunization with cytotoxic T cell epitope SPSYVYHQF (AH1), derived from MuLV gp70 envelope protein expressed by CT26 tumor cells, does not protect BALB/c mice against challenge with CT26 tumor cells. By contrast, immunization with AH1 plus T helper peptides OVA(323-337) or SWM(106-118) eliciting Th1 and Th0 profiles, protected 83% and 33% of mice, respectively. Interestingly, immunization with AH1 plus both helper peptides reverted the efficacy to 33%. We identified the endogenous T helper peptide p(320-333) from gp70 which elicits a Th1 profile and is naturally processed. As for OVA(323-337), immunization with p(320-333) alone did not protect against tumor challenge. However, p(320-333) plus AH1 protected 89% of mice at day 10 after vaccination. Only 20% of mice vaccinated with AH1 + OVA(323-337) or AH1 + p(320-333) were protected when challenged 80 days after immunization. Treatment with OVA(323-337) or with p(320-333) around established tumors delayed tumor growth. Our results show that tumor-related as well as tumor-unrelated but strong Th1 peptides may be useful for inducing CTL responses in tumor immunotherapy

Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses against Hepatocellular Carcinoma

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased upon combination with ICPI. Therefore, CIRP-based vaccines may generate anti-tumor immunity to enhance ICPI efficacy in HCC, although blockade of additional checkpoint molecules and immunosuppressive targets should be also considered

A first-principles approach to electrical transport in atomic-scale nanostructures

We present a first-principles numerical implementation of Landauer formalism for electrical transport in nanostructures characterized down to the atomic level. The novelty and interest of our method lies essentially on two facts. First of all, it makes use of the versatile Gaussian98 code, which is widely used within the quantum chemistry community. Secondly, it incorporates the semi-infinite electrodes in a very generic and efficient way by means of Bethe lattices. We name this method the Gaussian Embedded Cluster Method (GECM). In order to make contact with other proposed implementations, we illustrate our technique by calculating the conductance in some well-studied systems such as metallic (Al and Au) nanocontacts and C-atom chains connected to metallic (Al and Au) electrodes. In the case of Al nanocontacts the conductance turns out to be quite dependent on the detailed atomic arrangement. On the contrary, the conductance in Au nanocontacts presents quite universal features. In the case of C chains, where the self-consistency guarantees the local charge transfer and the correct alignment of the molecular and electrode levels, we find that the conductance oscillates with the number of atoms in the chain regardless of the type of electrode. However, for short chains and Al electrodes the even-odd periodicity is reversed at equilibrium bond distances.Comment: 14 pages, two-column format, submitted to PR