HLA-G: expression in human keratinocytes in vitro and in human skin in vivo

Classical, polymorphic major histocompatibility complex class I molecules are expressed on most nucleated cells.They present peptides at the cell surface and, thus, enable the immune system to scan peptides for their antigenicity. The function of the other, nonclassical class I molecules in man is controversial. HLA-G which has been shown by transfection experiments to be expressed at the cell surface, is only transcribed in placental tissue and in the fetal eye.Therefore, a role of HLA-G in the control of rejection of the allogeneic fetus has been discussed. We found that HLA-G expression is induced in keratinocytes by culture in vitro. Three different alternative splicing products of HLA-G can be detected: a full length transcript, an mRNA lacking exon 3 and a transcript devoid of exon 3 and 4. Reverse transcription followed by polymerase chain reaction also revealed the presence of HLA-G mRNA in vivo in biopsies of either diseased or healthy skin

What has finite element analysis taught us about diabetic foot disease and its management?:a systematic review

Over the past two decades finite element (FE) analysis has become a popular tool for researchers seeking to simulate the biomechanics of the healthy and diabetic foot. The primary aims of these simulations have been to improve our understanding of the foot's complicated mechanical loading in health and disease and to inform interventions designed to prevent plantar ulceration, a major complication of diabetes. This article provides a systematic review and summary of the findings from FE analysis-based computational simulations of the diabetic foot.A systematic literature search was carried out and 31 relevant articles were identified covering three primary themes: methodological aspects relevant to modelling the diabetic foot; investigations of the pathomechanics of the diabetic foot; and simulation-based design of interventions to reduce ulceration risk.Methodological studies illustrated appropriate use of FE analysis for simulation of foot mechanics, incorporating nonlinear tissue mechanics, contact and rigid body movements. FE studies of pathomechanics have provided estimates of internal soft tissue stresses, and suggest that such stresses may often be considerably larger than those measured at the plantar surface and are proportionally greater in the diabetic foot compared to controls. FE analysis allowed evaluation of insole performance and development of new insole designs, footwear and corrective surgery to effectively provide intervention strategies. The technique also presents the opportunity to simulate the effect of changes associated with the diabetic foot on non-mechanical factors such as blood supply to local tissues.While significant advancement in diabetic foot research has been made possible by the use of FE analysis, translational utility of this powerful tool for routine clinical care at the patient level requires adoption of cost-effective (both in terms of labour and computation) and reliable approaches with clear clinical validity for decision making

Ongoing methane discharge at well site 22/4b (North Sea)and discovery of a spiral vortex bubble plume motion

Highlights • Mega ebullition of biogenic methane from an abandoned offshore gas well, North Sea. • Evidence for midwater bubble plume intrusion, fallback, and short-circuiting of the plume. • Effective trapping of seabed released methane underneath the thermocline. • First observation of a spiral vortex methane plume and marginal turbulences. • Megaplumes appear less efficient in terms of vertical methane transport than previously thought. Abstract First direct evidence for ongoing gas seepage activity on the abandoned well site 22/4b (Northern North Sea, 57°55′ N, 01°38′ E) and discovery of neighboring seepage activity is provided from observations since 2005. A manned submersible dive in 2006 discovered several extraordinary intense seepage sites within a 60 m wide and 20 m deep crater cut into the flat 96 m deep seafloor. Capture and (isotope) chemical analyses of the gas bubbles near the seafloor revealed in situ concentrations of methane between 88 and 90%Vol. with δ13C–CH4 values around −74‰ VPDB, indicating a biogenic origin. Bulk methane concentrations throughout the water column were assessed by 120 Niskin water samples showing up to 400.000 nM CH4 in the crater at depth. In contrast, concentrations above the thermocline were orders of magnitude lower, with a median value of 20 nM. A dye tracer injection into the gas seeps revealed upwelling bubble and water motion with gas plume rise velocities up to ∼1 ms−1 (determined near the seabed). However, the dissolved dye did not pass the thermocline, but returned down to the seabed. Measurements of direct bubble-mediated atmospheric flux revealed low values of 0.7 ± 0.3 kty−1, much less than current state-of-the-art bubble dissolution models would predict for such a strong and upwelling in situ gas bubble flux at shallow water depths (i.e. ∼100 m). Acoustic multibeam water column imaging data indicate a pronounced 200 m lateral intrusion at the thermocline together with high methane concentration at this layer. A partly downward-orientated bubble plume motion is also visible in the acoustic data with potential short-circuiting in accordance to the dye experiment. This observation could partly explain the observed trapping of most of the released gas below the well-established thermocline in the North Sea. Moreover, 3D analyses of the multibeam water column data reveal that the upwelling plume transforms into a spiral expanding vortex while rising through the water column. Such a spiral vortex motion has never been reported before for marine gas seepage and might represent an important process with strong implication on plume dynamics, dissolution behavior, gas escape to the atmosphere, and is considered very important for respective modeling approaches

Preventing foot ulceration in diabetes:systematic review and meta-analyses of RCT data

Aims/hypothesis: Foot ulceration is a serious complication for people with diabetes that results in high levels of morbidity for individuals and significant costs for health and social care systems. Nineteen systematic reviews of preventative interventions have been published, but none provides a reliable numerical summary of treatment effects. The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to make the best possible use of the currently available data. Methods: We conducted a systematic review and meta-analysis of RCTs of preventative interventions for foot ulceration. OVID MEDLINE and EMBASE were searched to February 2019 and the Cochrane Central Register of Controlled Trials to October 2018. RCTs of interventions to prevent foot ulcers in people with diabetes who were free from foot ulceration at trial entry were included. Two independent reviewers read the full-text articles and extracted data. The quality of trial reporting was assessed using the Cochrane Risk of Bias tool. The primary outcome of foot ulceration was summarised using pooled relative risks in meta-analyses. Results: Twenty-two RCTs of eight interventions were eligible for analysis. One trial of digital silicone devices (RR 0.07 [95% CI 0.01, 0.55]) and meta-analyses of dermal infrared thermometry (RR 0.41 [95% CI 0.19, 0.86]), complex interventions (RR 0.59 [95% CI 0.38, 0.90], and custom-made footwear and offloading insoles (RR 0.53 [95% CI 0.33, 0.85]) showed beneficial effects for these interventions. Conclusions/interpretation: Four interventions were identified as being effective in preventing foot ulcers in people with diabetes, but uncertainty remains about what works and who is most likely to benefit

Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112

Human cytomegalovirus (HCMV) UL141 induces protection against natural killer cell-mediated cytolysis by downregulating cell surface expression of CD155 (nectin-like molecule 5; poliovirus receptor), a ligand for the activating receptor DNAM-1 (CD226). However, DNAM-1 is also recognized to bind a second ligand, CD112 (nectin-2). We now show that HCMV targets CD112 for proteasome-mediated degradation by 48 h post-infection, thus removing both activating ligands for DNAM-1 from the cell surface during productive infection. Significantly, cell surface expression of both CD112 and CD155 was restored when UL141 was deleted from the HCMV genome. While gpUL141 alone is sufficient to mediate retention of CD155 in the endoplasmic reticulum, UL141 requires assistance from additional HCMV-encoded functions to suppress expression of CD112