Electromechanical delay of the knee extensor muscles is not altered after harvesting the patellar tendon as a graft for ACL reconstruction: implications for sports performance

Although the scar tissue, which heals the donor site defect, has different elasticity from the neighbouring patellar tissue, it remains unclear if this scar tissue can lead to the changes of the electromechanical delay (EMD) of the knee extensor muscles. If such changes do exist, they can possibly affect both the utilization of the stored energy in the series elastic component, as well as the optimal performance of the knee joint movement. The purpose of this study was to investigate the influence of harvesting the patellar tendon during anterior cruciate ligament (ACL) reconstruction and the associated patellar tendon scar tissue development on the EMD of the rectus femoris (RF) and vastus medialis (VM) muscles. Seventeen patients who underwent an ACL reconstruction using the medial third of the patellar tendon were divided in two groups based upon their postoperative time interval. Maximal voluntary contraction from the knee extensors, surface EMG activity, and ultrasonographic measurements of the patellar tendon cross-section area were obtained from both knees. Our results revealed that no significant changes for the maximal voluntary contraction of the knee extensors and for the EMD of the RF and the VM muscles due to patellar scar tissue development after harvesting the tendon for ACL reconstruction. The EMD, as a component of the stretch reflex, is important for the utilization of the stored energy in the series elastic component and thus, optimal sports performance. However, from our results, it can be implied that the ACL reconstruction using a patellar tendon graft would not impair sports performance as far as EMD is concerned

537Microparticles and exosomes differentially impact on endothelial cell function in coronary artery disease

Background and Purpose: Microparticles (MPs) and exosomes are released by cells using different mechanisms. Thus, quantitative as well as qualitative changes of both particle populations, MPs and exosomes, in patients with coronary artery disease (CAD) might reflect an altered activation status of the endothelium, platelets and leukocytes. Moreover, they might exert differential effects on the target organs, such as the endothelium. Yet, alterations in both populations have not been studied side-by-side so far. The aim of the study was to compare the impact of MPs and exosomes from healthy subjects and CAD patients on endothelial cell (EC) functional characteristics. Methods: MPs and exosomes were isolated by stepwise filtration and ultracentrifugation from citrate-plasma and verified by electron microscopy and dynamic light scattering. MP and exosome fractions, as well as the vehicle (PBS), were added to human arterial ECs and EC apoptosis, number, size, capacity for in vitro-reendothelialisation after scratching, expression of adhesion molecules ICAM-1 and VCAM-1 were assessed. In parallel, platelet-, endothelial- and leukocyte-derived MPs were quantified. In a separate sub-study, the same parameters were assessed in plasma of CAD patients undergoing standard medical rehabilitation or an exercise-based cardiac rehabilitation programme. Results: MPs of healthy, but not of CAD patients supported in vitro re-endothelialisation, while exosomes had no influence. Exercise, but not standard rehabilitation improved CAD MP capacity to support in vitro rehabilitation. This was negatively correlated to the number of leukocyte- and endothelial-derived MPs, but not total or platelet MPs. EC number was negatively affected by exposure to CAD MPs. ANCOVA analysis identified disease, but not the particle type as influencing factor. Instead, apoptotic cell death was influenced by particle type, but not by the disease, and was not altered in rehabilitation. Similarly, ICAM-1 and VCAM-1 expression were enhanced on ECs after incubation with exosomes, but not with MPs, with no effect of disease or rehabilitation. Conclusion: MPs and exosomes differentially affect endothelial cell function and underlie differential modulation in disease and rehabilitation. Those findings might in the future help to optimize and monitor cardiovascular therap

Late Maastrichtian carbon isotope stratigraphy and cyclostratigraphy of the Newfoundland Margin (Site U1403, IODP Expedition 342)

Earth’s climate during the Maastrichtian (latest Cretaceous) was punctuated by brief warming and cooling episodes, accompanied by perturbations of the global carbon cycle. Superimposed on a long-term cooling trend, the middle Maastrichtian is characterized by deep-sea warming and relatively high values of stable carbon-isotope ratios, followed by strong climatic variability towards the end of the Cretaceous. A lack of knowledge on the timing of climatic change inhibits our understanding of underlying causal mechanisms. We present an integrated stratigraphy from Integrated Ocean Drilling Program (IODP) Site U1403, providing an expanded deep ocean record from the North Atlantic (Expedition 342, Newfoundland Margin). Distinct sedimentary cyclicity suggests that orbital forcing played a major role in depositional processes, which is confirmed by statistical analyses of high resolution elemental data obtained by X-ray fluorescence (XRF) core scanning. Astronomical calibration reveals that the investigated interval encompasses seven 405-kyr cycles (Ma4051 to Ma4057) and spans the 2.8 Myr directly preceding the Cretaceous/Paleocene (K/Pg) boundary. A high-resolution carbon-isotope record from bulk carbonates allows us to identify global trends in the late Maastrichtian carbon cycle. Low-amplitude variations (up to 0.4‰) in carbon isotopes at Site U1403 match similar scale variability in records from Tethyan and Pacific open-ocean sites. Comparison between Site U1403 and the hemipelagic restricted basin of the Zumaia section (northern Spain), with its own well-established independent cyclostratigraphic framework, is more complex. Whereas the pre-K/Pg oscillations and the negative values of the Mid-Maastrichtian Event (MME) can be readily discerned in both the Zumaia and U1403 records, patterns diverge during a ~ 1 Myr period in the late Maastrichtian (67.8–66.8 Ma), with Site U1403 more reliably reflecting global carbon cycling. Our new carbon isotope record and cyclostratigraphy offer promise for Site U1403 to serve as a future reference section for high-resolution studies of late Maastrichtian paleoclimatic change

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

Survival of adult neurons lacking cholesterol synthesis in vivo

BACKGROUND: Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. RESULTS: Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. CONCLUSION: We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system

Atlantic Salmon Reovirus Infection Causes a CD8 T Cell Myocarditis in Atlantic Salmon (Salmo salar L.)

Heart and skeletal inflammation (HSMI) of farmed Atlantic salmon (Salmo salar L.) is a disease characterized by a chronic myocarditis involving the epicardium and the compact and spongious part of the heart ventricle. Chronic myositis of the red skeletal muscle is also a typical finding of HSMI. Piscine reovirus (PRV) has been detected by real-time PCR from farmed and wild salmon with and without typical changes of HSMI and thus the causal relationship between presence of virus and the disease has not been fully determined [1]. In this study we show that the Atlantic salmon reovirus (ASRV), identical to PRV, can be passaged in GF-1 cells and experimental challenge of naïve Atlantic salmon with cell culture passaged reovirus results in cardiac and skeletal muscle pathology typical of HSMI with onset of pathology from 6 weeks, peaking by 9 weeks post challenge. ASRV replicates in heart tissue and the peak level of virus replication coincides with peak of heart lesions. We further demonstrate mRNA transcript assessment and in situ characterization that challenged fish develop a CD8+ T cell myocarditis

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays

Background Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma. Methods After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features. Results CD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013). Conclusions This study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma

On impact and volcanism across the Cretaceous-Paleogene boundary

The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism