HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef's influence on in vivo recirculation of T lymphocytes, we assessed lymph-node homing of Nef-expressing primary murine lymphocytes and found a drastic impairment in homing to peripheral lymph nodes. Intravital imaging and 3D immunofluorescence reconstruction of lymph nodes revealed that Nef potently impaired T-lymphocyte extravasation through high endothelial venules and reduced subsequent parenchymal motility. Ex vivo analyses of transendothelial migration revealed that Nef disrupted T-lymphocyte polarization and interfered with diapedesis and migration in the narrow subendothelial space. Consistently, Nef specifically affected T-lymphocyte motility modes used in dense environments that pose high physical barriers to migration. Mechanistically, inhibition of lymph node homing, subendothelial migration and cell polarization, but not diapedesis, depended on Nef's ability to inhibit host cell actin remodeling. Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor.

Extracorporeal membrane oxygenation as a bridge to diagnosis in a 20-month old girl with pulmonary hypertension and right ventricular failure

A 20-month old girl with severe pulmonary hypertension and cardiomegaly was admitted to the paediatric intensive care unit with right ventricular failure of unknown origin. Only after decompression of the heart chambers under extracorporeal membrane oxygenation (ECMO), did the pathognomonic membrane of Cor triatriatum become visible on echocardiography. The patient underwent successful surgical correction and subsequently cardiac function recovered completely. Cor triatriatum remains a rare congenital cardiac disorder with a variable presentation, often including recurrent respiratory infections before right-sided heart failure occurs. This case illustrates that ECMO can serve not only as a bridge to diagnosis, but can also facilitate correct diagnosis. Given the excellent outcome after surgical treatment, it is crucial that cardiologists rule out the possibility of cor triatriatum when assessing a child with unexplained pulmonary hypertension.

Direct Quantitative Assessment of the Peripheral Artery Collateral Circulation in Patients Undergoing Angiography

Despite the fact that numerous studies pursued the strategy of improving collateral function in patients with peripheral artery disease (PAD), there is currently no method available to quantify collateral arterial function of the lower limb.

Hemodynamic Modeling of the Intrarenal Circulation

Three dimensional, time dependent numerical simulations of healthy and pathological conditions in a model kidney were performed. Blood flow in a kidney is not commonly investigated by computational approach, in contrast for example, to the flow in a heart. The flow in a kidney is characterized by relatively small Reynolds number (100 < Re < 0.01-laminar regime). The presented results give insight into the structure of such flow, which is hard to measure in vivo. The simulations have suggested that venous thrombosis is more likely than arterial thrombosis-higher shear rate observed. The obtained maximum velocity, as a result of the simulations, agrees with the observed in vivo measurements. The time dependent simulations show separation regimes present in the vicinity of the maximum pressure value. The pathological constriction introduced to the arterial geometry leads to the changes in separation structures. The constriction of a single vessel affects flow in the whole kidney. Pathology results in different flow rate values in healthy and affected branches, as well as, different pulsate cycle characteristic for the whole system.

Simulated winter circulation types in the North Atlantic and European region for preindustrial and glacial conditions

[1] Winter circulation types under preindustrial and glacial conditions are investigated and used to quantify their impact on precipitation. The analysis is based on daily mean sea level pressure fields of a highly resolved atmospheric general circulation model and focuses on the North Atlantic and European region. We find that glacial circulation types are dominated by patterns with an east-west pressure gradient, which clearly differs from the predominantly zonal patterns for the recent past. This is also evident in the frequency of occurrence of circulation types when projecting preindustrial circulation types onto the glacial simulations. The elevation of the Laurentide ice sheet is identified as a major cause for these differences. In areas of strong precipitation signals in glacial times, the changes in the frequencies of occurrence of the circulation types explain up to 60% of the total difference between preindustrial and glacial simulations.

On the relationship between Nd isotopic composition and ocean overturning circulation in idealized freshwater discharge events

Using a cost-efficient climate model, the effect of changes in overturning circulation on neodymium isotopic composition,ϵNd, is systematically examined for the first time. Idealized sequences of abrupt climate changes are induced by the application of periodic freshwater fluxes to the North Atlantic (NA) and the Southern Ocean (SO), thus mainly affecting either the formation of North Atlantic Deep Water (NADW) or Antarctic Bottom Water (AABW). Variations in ϵNd reflect weakening and strengthening of the formation of NADW and AABW, changes in ϵNdof end-members are relatively small. Relationships betweenϵNd and the strength of NADW or AABW are more pronounced for AABW than for NADW. Atlantic patterns of variations in ϵNd systematically differ between NA and SO experiments. Additionally, the signature of changes in ϵNd in the Atlantic and the Pacific is alike in NA but opposite in SO experiments. Discrimination between NA and SO experiments is therefore possible based on the Atlantic pattern of variations in ϵNd and the contrariwise behavior of ϵNd in the Atlantic and the Pacific. In further experiments we examined the effect of variations in magnitudes of particle export fluxes. Within the examined range, and although settling particles represent the only sink of Nd, their effects on ϵNd are relatively small. Our results confirm the large potential of ϵNd as a paleocirculation tracer but also indicate its limitations of quantitative reconstructions of changes in the Atlantic Meridional Ocean Circulation.

Histomorphologic evaluation of extracorporeal shock wave therapy of the fourth metatarsal bone and the origin of the suspensory ligament in horses without lameness

OBJECTIVE: To determine via histologic examination and scintigraphy the effect of focused extracorporeal shock wave therapy (ESWT) on normal bone and the bone-ligament interface in horses. ANIMALS: 6 horses without lameness. PROCEDURE: Origins of the suspensory ligament at the metacarpus (35-mm probe depth) and fourth metatarsal bone (5-mm probe depth) were treated twice (days 0 and 16) with 2,000 shocks (energy flux density, 0.15 mJ/mm2). One forelimb and 1 hind limb were randomly treated, and the contralateral limbs served as nontreated controls. Bone scans were performed on days -1 (before ESWT), 3, 16, and 19. Histomorphologic studies of control and treated tissues were performed on day 30. RESULTS: ESWT significantly increased the number of osteoblasts but caused no damage to associated soft tissue structures and did not induce cortical microfractures. A significant correlation between osteoblast numbers and radiopharmaceutical uptake was noticed on lateral views of the hind limb on days 3 and 16 and on caudal views of the forelimb on day 3. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ESWT has the potential to increase osteoblast numbers in horses. The correlation between increased osteoblast numbers and radio-pharmaceutical uptake 3 days and 16 days after the first ESWT suggested that stimulation of osteogenesis occurred soon after ESWT. No damage to bone or the bone-ligament interface should occur at the settings used in this study, and ESWT can therefore be administered safely in horses.