Flt3-ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)-4- and VLA-5-dependent mechanism

The adhesion of haematopoietic progenitor cells (HPC) to the bone marrow microenvironment is a process regulated by cytokines. In this study, we have shown that flt3-ligand (FL), a growth factor that controls early haematopoiesis, regulated the function and expression of the beta-1 integrins, very late antigen (VLA)-4 and VLA-5 on HPC. The modulation of the adhesiveness of HPC by FL was studied by adhesion assays on umbilical vein endothelial cells (HUVEC). Stimulation by FL induced two peaks of increased adhesiveness of HPC. The first peak was at around 30 min and was mechanistically related to an activation of the beta-1 integrins, mainly VLA-4 and VLA-5. The second peak was at around 12 h and was related to increased expression of VLA-4 and VLA-5. The control of HPC adhesiveness by FL is a previously unreported property of FL that may be important for the homing and the retention of flt3-expressing HPC within the bone marrow microenvironment.     

Lymphocytic hypophysitis with lachrymal, salivary and thyroid gland involvement

We report on hypophysitis associated with a prominent lymphoid infiltration of salivary and lachrymal glands in a 35-year-old woman with a dramatic response to steroids. Four years later, overt Graves' disease developed. To our knowledge, pseudotumoral lymphocytic infiltration of both lachrymal and salivary glands has never been described in association with hypophysitis. Benign lymphocytic hypophysitis may belong to a spectrum that extends from low-grade lymphoid proliferation to autoimmune disease. Such a process may follow a regional tissue distribution including pituitary, thyroid, lachrymal and salivary glands.     

Transient enriched housing before amyloidosis onset sustains cognitive improvement in Tg2576 mice

Levels of educational and occupational attainment, as components of cognitive reserve, may modify the relationship between the pathological hallmarks and cognition in Alzheimer's disease (AD). We examined whether exposure of a Tg2576 transgenic mouse model of AD to environmental enrichment (EE) at a specific period during the amyloidogenic process favored the establishment of a cognitive reserve. We found that exposure to EE during early adulthood of Tg2576 mice—before amyloidogenesis has started—reduced the severity of AD-related cognitive deficits more efficiently than exposure later in life, when the pathology is already present. Interestingly, early-life exposure to EE, while slightly reducing forebrain surface covered by amyloid plaques, did not significantly impact aberrant inhibitory remodeling in the hippocampus of Tg2576 mice. Thus, transient early-life exposure to EE exerts long-lasting protection against cognitive impairment during AD pathology. In addition, these data define the existence of a specific life time frame during which stimulatory activity most efficiently builds a cognitive reserve, limiting AD progression and favoring successful aging.     

Effect of a single, open-sea, air scuba dive on human micro- and macrovascular function

Purpose

Previous studies have shown that bubble formation induced endothelial damage on conduit arteries. We aim to evaluate the effect of diving on microvascular and macrovascular function.

Methods

Nine divers took part in a SCUBA dive at 30 msw (400 kPa), for 30 min of bottom time. Pre- and post-dive, they underwent an assessment of endothelial-dependent (acetylcholine) and endothelial-independent (sodium nitroprusside) microvascular function (laser Doppler flowmetry), as well as endothelial-dependent (flow-mediated dilation) and endothelial-independent (nitroglycerin-mediated dilation) function. Bubble grades were monitored with Doppler according to the Spencer grade.

Results

The mean KISS bubble score ranged from 21.10 ± 4.7 at rest to 55.03 ± 8.8 after knee flexion. The increase in cutaneous vascular conductance elicited by either acetylcholine (25.34 ± 6.71 to 7.63 ± 1.25 %, p = 0.021) or sodium nitroprusside (35.24 ± 8.75 to 7.61 ± 1.86 %, p = 0.017) was significantly reduced after diving. Similarly, both flow-mediated dilation (10.8 ± 0.9 to 5.4 ± 1.5 %, p = 0.002) and nitroglycerin-mediated dilation (15 ± 1.1 to 6.5 ± 1.6 %, p = 0.002) were also significantly decreased. There were no correlations between vascular parameters and bubble formation.

Conclusions

There appears to be a reduction in endothelium-dependent and endothelium-independent, macro- and microvascular function associated with diving. Our results suggest that in the process of vascular dysfunction during diving, functional changes in the vessel wall may not be limited to the endothelium and may be mediated by alterations in vascular smooth muscle.     

The Immediate Effects of Foam Rolling and Stretching on Iliotibial Band Stiffness: A Randomized Controlled Trial

BackgroundIliotibial Band Syndrome (ITBS) is a common clinical condition likely caused by abnormal compressive forces to the iliotibial band (ITB). Stretching interventions are common in ITBS treatment and may predominantly affect tensor fascia latae (TFL). Another ITBS treatment is foam rolling, which may more directly affect the ITB. Shear wave ultrasound elastography (SWUE) measures real-time soft tissue stiffness, allowing tissue changes to be measured and compared.PurposeTo examine effects of foam rolling and iliotibial complex stretching on ITB stiffness at 0˚ and 10˚ of hip adduction and hip adduction passive range of motion (PROM).Study DesignRandomized controlled trial.MethodsData from 11 males (age = 30.5 ± 9.0 years, Body Mass Index (BMI) = 27.8 ± 4.0) and 19 females (age = 23.5 ± 4.9, BMI = 23.2 ± 2.1) were analyzed for this study. Subjects were randomly assigned to one of three groups: control, stretching, and foam rolling. Shear wave ultrasound elastography measurements included ITB Young’s modulus at the mid-thigh, the distal femur and the TFL muscle belly. ITB-to-femur depth was measured at mid-thigh level. Hip adduction PROM was measured from digital images taken during the movement.ResultsNo significant interactions or main effects were found for group or time differences in ITB Young’s modulus at the three measured locations. The ITB stiffness at the mid-thigh and distal femur increased with 10° adduction, but TFL stiffness did not increase. A main effect for adduction PROM was observed, where PROM increased 0.8˚ post-treatment (p = 0.02).ConclusionA single episode of stretching and foam rolling does not affect short-term ITB stiffness. The lack of ITB stiffness changes may be from an inadequate intervention stimulus or indicate that the interventions have no impact on ITB stiffness.Levels of Evidence1b     

The domain structure of protoporphyrinogen oxidase, the molecular target of diphenyl ether-type herbicides

Protoporphyrinogen oxidase (EC 1–3-3–4), the 60-kDa membrane-bound flavoenzyme that catalyzes the final reaction of the common branch of the heme and chlorophyll biosynthesis pathways in plants, is the molecular target of diphenyl ether-type herbicides. It is highly resistant to proteases (trypsin, endoproteinase Glu-C, or carboxypeptidases A, B, and Y), because the protein is folded into an extremely compact form. Trypsin maps of the native purified and membrane-bound yeast protoporphyrinogen oxidase show that this basic enzyme (pI > 8.5) was cleaved at a single site under nondenaturing conditions, generating two peptides with relative molecular masses of 30,000 and 35,000. The endoproteinase Glu-C also cleaved the protein into two peptides with similar masses, and there was no additional cleavage site under mild denaturing conditions. N-terminal peptide sequence analysis of the proteolytic (trypsin and endoproteinase Glu-C) peptides showed that both cleavage sites were located in putative connecting loop between the N-terminal domain (25 kDa) with the βαβ ADP-binding fold and the C-terminal domain (35 kDa), which possibly is involved in the binding of the isoalloxazine moiety of the FAD cofactor. The peptides remained strongly associated and fully active with the K_m for protoporphyrinogen and the K_i for various inhibitors, diphenyl-ethers, or diphenyleneiodonium derivatives, identical to those measured for the native enzyme. However, the enzyme activity of the peptides was much more susceptible to thermal denaturation than that of the native protein. Only the C-terminal domain of protoporphyrinogen oxidase was labeled specifically in active site-directed photoaffinity-labeling experiments. Trypsin may have caused intramolecular transfer of the labeled group to reactive components of the N-terminal domain, resulting in nonspecific labeling. We suggest that the active site of protoporphyrinogen oxidase is in the C-terminal domain of the protein, at the interface between the C- and N-terminal domains.