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Mutations in this gene have been reported in patients with poikiloderma and neutropenia, with a few reported cases in association with skin fragility, a condition distinct from the KEB phenotype. Transcriptome analysis revealed that several genes, expressed in the cutaneous basement membrane zone and previously associated with different subtypes of EB, were differentially downregulated at the mRNA level. EB-associated mRNA downregulation was confirmed at protein levels by skin immunofluorescence. These observations provide a novel mechanism for blistering and erosions in the skin as a result reduced presence of adhesion complexes critical for stable association of epidermis and dermis at the level of cutaneous basement membrane zone.Benthic animals inhabiting the edges of marine oxygen minimum zones (OMZ) are exposed to unpredictable large fluctuations of oxygen levels. SKF38393 Sessile organisms including bivalves must depend on physiological adaptations to withstand these conditions. However, as habitats are rather inaccessible, physiological adaptations of the OMZ margin inhabitants to oxygen fluctuations are not well understood. We therefore investigated the transcriptional responses of selected key genes involved in energy metabolism and stress protection in a dominant benthic species of the northern edge of the Namibian OMZ, the nuculanid clam Lembulus bicuspidatus,. We exposed clams to normoxia (~5.8 ml O2 l-1), severe hypoxia (36 h at ~0.01 ml O2 l-1) and post-hypoxic recovery (24 h of normoxia following 36 h of severe hypoxia). Using newly identified gene sequences, we determined the transcriptional responses to hypoxia and reoxygenation of the mitochondrial aerobic energy metabolism (pyruvate dehydrogenase E1 complex, cytochrome c oxidaquality control mechanisms in responses to oxygen fluctuations of the OMZ bivalve L.bicuspidatus. The reaction of L.bicuspidatus to oxygen fluctuations implies parallels to that of other hypoxia-tolerant bivalves, such as intertidal species.Cone photoreceptors are the first neurons along the visual pathway that exhibit center-surround antagonistic receptive fields, the basic building blocks for spatial information processing in the visual system. The surround responses in cones are mediated by the horizontal cells (HCs) via multiple feedback synaptic mechanisms. It has been controversial on which mechanisms are responsible for the surround-elicited depolarizing responses in cones (ΔVCone(s)), and whether the surround responses of various types of cones are mediated by the same HC feedback mechanisms. In this report, we studied ΔVCone(s)) of four types of cones in the salamander retina, and found that they are mediated by feedback synapses from A-type, B-type or A- and B-type HCs. ΔVCone(s) are observable in the presence of concomitant center light spots, and surround + center light stimuli of various intensity, size and wavelength differentially activate the feedback synapses from A- and B-type HCs to cones. We found that ΔVCone(s) of the L-cones are mediated by both A- and B-type HCs, those of the P- and S-cones by B-type HCs, and those of the A-cones by the A-type HCs. Moreover, our results suggest that B-type HCs mediate ΔVCone(s) through both GABAergic and GluT-ClC feedback synaptic mechanisms, and A-type HCs mediate ΔVCone(s) via the GluT-ClC feedback mechanism. Feedback synaptic mechanisms that increase calcium influx in cone synaptic terminals play important roles in mediating the antagonistic surround responses in the postsynaptic bipolar cells, but they may not generate enough current to depolarize the cones and significantly contribute to ΔVCone(s).The regulations of endothelial permeability and vascular tone by sphingosine 1-phosphate (S1P) have been well-studied independently. Little is known about whether the effects of S1P on endothelial permeability can directly influence vascular tone in resistance arteries, which impact blood flow. The endothelium forms a partial barrier that regulates access of circulating agonists to underlying vascular smooth muscle cells (VSMCs). We hypothesized that physiological concentrations of circulating S1P simultaneously control endothelial barrier function and vascular tone through endothelial production of nitric oxide (NO). We adapted the pressure myograph system to simultaneously measure both functions in pressurized mesenteric compared to uterine resistance arteries from wild-type and eNOS KO mice. We established that 1) S1P interacting directly with the endothelium inside pressurized arteries generates NO that limits endothelial permeability; 2) an intact endothelium forms a partial physical barrier that regulates access of intraluminal S1P to the underlying VSMCs and 3) S1P infused lumenally also generates NO through eNOS that counterbalances the constriction induced by S1P that is able to access VSMCs and this is critical to control vascular tone. We conclude that targeting the S1P signaling system, particularly the capacity to produce NO could be clinically important in the treatment of vascular diseases.Prior research has shown that Open Label Placebos (OLPs; that is, placebos described honestly as inactive pills) are effective for a variety of clinical conditions, including pain. However, little is known about patient attitudes towards OLPs. We conducted qualitative interviews with n = 11 patients (73% female) who recently had hand or wrist surgery and took ≥ 1 opioid pill. Interview topics included pain management, the placebo effect, and in particular, attitudes towards OLPs. Interviews were analyzed inductively and content-coded. Five themes were identified 1) Role of the mind in pain and illness, 2) Shortcomings of opioids are the strengths of OLPs, 3) Perceptions of OLP effectiveness, 4) Relational aspects of OLP administration, and 5) Practical considerations for OLP implementation. Most patients agreed that, because of their transparency, OLPs are ethical. Participants indicated some degree of reluctance about using OLPs, but the majority said they would take OLPs if prescribed by a doctor. Patients noted that the primary disadvantage of opioids is their potency, which can lead to addiction or side-effects; by contrast, the primary advantage of placebos is their inertness. Results suggest that OLPs appear to be well received as a postoperative pain treatment among the patients in this study. PERSPECTIVE This qualitative study examines how hand surgery patients view OLPs, which are placebos described honestly as inactive pills. OLPs were generally well received by patients as a treatment for pain after surgery and could be considered as an adjunctive treatment to potentially reduce reliance on prescription opioids.
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