In homeostasis, cellular processes are in a dynamic equilibrium. Perturbation of homeostasis causes stress. In this review I summarize how perturbation of three major functions of the endoplasmic ...reticulum (ER) in eukaryotic cells-protein folding, lipid and sterol biosynthesis, and storing intracellular Ca²⁺ - causes ER stress and activates signaling pathways collectively termed the unfolded protein response (UPR). I discuss how the UPR reestablishes homeostasis, and summarize our current understanding of how the transition from protective to apoptotic UPR signaling is controlled, and how the UPR induces inflammatory signaling.
The Weddell Gyre (WG) is one of the main oceanographic features of the Southern Ocean south of the Antarctic Circumpolar Current which plays an influential role in global ocean circulation as well as ...gas exchange with the atmosphere. We review the state‐of‐the art knowledge concerning the WG from an interdisciplinary perspective, uncovering critical aspects needed to understand this system's role in shaping the future evolution of oceanic heat and carbon uptake over the next decades. The main limitations in our knowledge are related to the conditions in this extreme and remote environment, where the polar night, very low air temperatures, and presence of sea ice year‐round hamper field and remotely sensed measurements. We highlight the importance of winter and under‐ice conditions in the southern WG, the role that new technology will play to overcome present‐day sampling limitations, the importance of the WG connectivity to the low‐latitude oceans and atmosphere, and the expected intensification of the WG circulation as the westerly winds intensify. Greater international cooperation is needed to define key sampling locations that can be visited by any research vessel in the region. Existing transects sampled since the 1980s along the Prime Meridian and along an East‐West section at ~62°S should be maintained with regularity to provide answers to the relevant questions. This approach will provide long‐term data to determine trends and will improve representation of processes for regional, Antarctic‐wide, and global modeling efforts—thereby enhancing predictions of the WG in global ocean circulation and climate.
Plain Language Summary
The Weddell Gyre is one of the main oceanographic features in the ocean surrounding Antarctica, the Southern Ocean. Although located far from other continents, this polar region affects the planet through the exchange of gases between frigid ocean waters and the atmosphere, regulating oxygen and carbon dioxide farther north. Studying the Weddell Gyre is challenging, as sea ice covers the ocean surface year around, restricting access by research ships and sensing of ocean surface from satellites. New technology is now available to avoid past limitations, autonomous underwater vehicles, instruments flown by planes, and floats instrumented with sea‐ice detection. Only through international collaboration can we obtain adequate data to populate environmental models and study key areas in the gyre or hot spots. In this review we identify the missing links in our knowledge of the gyre, proposing research to address those questions. Three aspects are critical to understanding the processes that drive the gyre's oceanography, ice, geology, chemistry, and biology: winter and under‐ice conditions that set the stage for the evolution of physics, ice, and biogeochemistry; exchange of water, material, and energy (or heat) with lower latitudes; and intensification of the clockwise circulation of the gyre with changes in winds.
Key Points
Major research priorities to advance understanding of the Weddell Gyre are identified and justified against current knowledge
Interdisciplinary approaches are needed to support system science research of the Weddell Gyre and promote collaborative projects
Winter conditions, connectivity to lower latitudes, and intensification of the gyre are the main interdisciplinary priorities
The Weddell Sea plays an important role for the global oceans and climate by being one of the biggest production and export areas of Antarctic Bottom Water (AABW). Circumpolar Deep Water (CDW) enters ...the Weddell Gyre (WG) at its eastern boundary. Then called Warm Deep Water (WDW), it is a major contributor to the formation of deep and bottom waters due to ocean-ice shelf interactions in the southern and soutwestern Weddell Sea. Hydrographic data collected between 0 and 30°E on the RV Polarstern cruise ANT XX/2 reveals a two-core structure for the eastern inflow of warm water at roughly 20°E but not further downstream at the Greenwich meridian (GM). Model results and climatological fields suggest that the two cores represent two separate modes of warm inflow. One mode is driven by eddy mixing in the northeastern corner of the WG and the other one is an advective mode, forming the southern branch of the inflow which extends beyond 30°E before turning westward. Both pathways are likely to carry waters from different origins within the Antarctic Circumpolar Current ACC, where more ventilated CDW is found at the Southern Boundary SB compared to the centre. The southern route shows considerable interannual variability in the model. A variable inflow of two types of CDW together with admixed recirculated and cooler waters from the Weddell Sea can potentially contribute to the observed variability and warming trend of WDW over the last decade at the GM.
•Hydrographic data reveals two warm cores at eastern inflow region of Weddell Gyre.•One advective and one eddy driven pathway as suggested in previous literature.•Interannual variability of advective pathway seems to be related to SAM index.•Inflow could originate from different regions within the ACC.•WDW at GM is mixture of different inflows from ACC and recirculated WDW.
Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high ...glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity.
Background Sweat is a major aggravating factor of atopic dermatitis (AD) and approximately 80% of patients with AD show type I hypersensitivity against sweat. Objective To identify and characterize ...an antigen in sweat that induces histamine release from basophils of patients with AD. Methods Basophil histamine-releasing activity in sweat was purified by a combination of chromatographies, and proteins were analyzed with mass spectrometry. Recombinant proteins of the sweat antigen were generated, and their biological characteristics were studied by immunoblots, histamine release tests, and neutralization assays. Results We identified a fungal protein, MGL_1304, derived from Malassezia globosa ( M globosa ) in the purified sweat antigen. Recombinant MGL_1304 induced histamine release from basophils of most of the patients with AD, in accordance with the semi-purified sweat antigen. Moreover, recombinant MGL_1304 abolished the binding of serum IgE of patients with AD to the semi-purified sweat antigen, or vice versa in immunoblot analysis, and attenuated the sensitization of RBL-48 mast cells expressing human FcɛRI by serum IgE. Studies of truncated mutants of MGL_1304 indicated that IgE of patients with AD recognized the conformational structure of MGL_1304 rather than short peptide sequences. Western blot analysis of the whole lysate, the culture supernatant of M globosa , and the semi-purified sweat antigen showed that MGL_1304 was produced as a minor immunological antigen of M globosa with posttranslational modification, cleaved, and secreted as a 17-kDa major histamine-releasing sweat antigen. Conclusion MGL_1304 is a major allergen in human sweat and could cause type I allergy in patients with AD.
Background
The currently mainly used techniques of primary ventral hernia repair have specific disadvantages and risks.
Methods
To minimize complications of the existing open and laparoscopic ...techniques of ventral hernia repair, the endoscopic-assisted or endoscopic Mini- or Less-Open Sublay (E/MILOS) concept was developed. This paper reports on our experience with the E/MILOS concept for the management of primary umbilical and epigastric hernias. All E/MILOS operations were prospectively documented in the German hernia registry “Herniamed”. For 1 year follow-up, all patients and their general practitioners received a questionnaire.
Results
Five hundred and twenty primary umbilical and 554 epigastric E/MILOS operations with complete 1-year follow-up were included. Concomitant RD were treated in 18.3% and 14.1% of the umbilical and epigastric hernia cohort, respectively. Total perioperative complication rates and reoperation rates were 1.2% and 0.9% for both umbilical and epigastric hernias, respectively. Infection rates were 0.0% and 0.2% after umbilical and epigastric hernia operations, respectively. Recurrence rates 1 year after E/MILOS umbilical and epigastric hernia were 0.0% and 0.5%, respectively. One year rates of chronic pain at rest, chronic pain during physical activities, and chronic pain requiring treatment after umbilical and epigastric hernia repair were 1.5% and 2.7%, 2.1% and 4.2%, and 0.6% and 1.8%; respectively.
Conclusion
The E/MILOS concept allows the endoscopically assisted (MILOS) or endoscopic (EMILOS) transhernial minimal invasive sublay mesh repair of primary umbilical and epigastric hernias with or without rectus diastasis with low complication, recurrence, and chronic pain rates.
Abstract Background The efficacy of bright light therapy is well established for winter depression but its status in depression without seasonal pattern is unclear. Methods We systematically ...evaluated available data on the efficacy of light therapy in nonseasonal depression. Results We identified 62 reports among which 15 met our predefined selection criteria. The available data show evidence for the efficacy of light therapy as an adjuvant treatment to antidepressants. Trials that evaluated light therapy alone (without antidepressants) in nonseasonal depression yielded inconsistent results. Limitations Most of the studies extracted poorly controlled the issue of blindness and were limited by small sample sizes. Publication bias may have distorted our estimation of the effect of light therapy. Conclusions Overall, bright light therapy is an excellent candidate for inclusion into the therapeutic inventory available for the treatment of nonseasonal depression today, as adjuvant therapy to antidepressant medication. Future clinical trials of light therapy should distinguish homogenous subgroups of depressed patients in order to evaluate whether light therapy may eventually be considered as stand-alone treatment for specific subgroups of patients with nonseasonal depression.
Tetraploid plants were produced by inducing chromosome doubling using colchicine in in vitro shoot tips of poplar and black locust clones. Many of the plants treated with colchicine showed modified ...morphological characteristics like stunted growth, thicker leaves and modified leaf morphology. The counting of chloroplast number in the epidermal guard cells of stomata was used for the rapid screening of tetraploids. The differences in mean chloroplast numbers between diploid and tetraploid plants were highly significant. For all plants tested, the tetraploid genotype had almost double the number of chloroplasts per guard cell compared to the diploid origin. Some plants were further analysed by flow cytometry to verify their ploidy status that was determined by chloroplast numbers. The results of this study demonstrated for the first time that chloroplast counting in poplar and black locust could be an effective and reliable method for pre-screening large numbers of plants for their ploidy level. The protocol might be applicable in a wide scope of breeding programs.
Human skin is permanently exposed to microorganisms, but rarely infected. One reason for this natural resistance might be the existence of a 'chemical barrier' consisting in constitutively and ...inducibly produced antimicrobial peptides and proteins (AMPs). Many of these AMPs can be induced in vitro by proinflammatory cytokines or bacteria. Apart from being expressed in vivo in inflammatory lesions, some AMPs are also focally expressed in skin in the absence of inflammation. This suggests that non-inflammatory stimuli of endogenous and/or exogenous origin can also stimulate AMP synthesis without inflammation. Such mediators might be ideal 'immune stimulants' to induce only the innate antimicrobial skin effector molecules without causing inflammation.
Autism Spectrum Disorder (ASD) diagnosis is relatively consensual in typical forms. The margins of the spectrum and their degree of extension, however, are controversial. This has far-reaching ...implications, which extend beyond theoretical considerations: first, peripheral forms of autism are more prevalent than central forms; second, we do not know how relevant typical-targeted recommendations are for atypical forms. In DSM-IV-TR, these margins of autism were studied within the category of Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). In spite of its low reliability, this former diagnosis was of particular interest to shed light on the gray area of margins. The aim of this systematic is therefore to investigate the clinical characteristics of PDD-NOS in comparison with Autistic Disorder.
A stepwise systematic PRISMA literature review was conducted by searching PubMed and Web Of Science databases to select corresponding studies.
The systematic review included 81 studies comprising 6,644 children with PDD-NOS. Cross-sectional and longitudinal studies comparing PDD-NOS and AD showed that PDD-NOS corresponds to milder form of autism with less impact and less associated disorder, with the exception of schizophrenia and mood disorder.
Our review challenges initial views of PDD-NOS, and shows the clinical relevance of this diagnosis when dealing with the margins of autism, and the
diversity included in the spectrum. However, in view of the many limitations of PDD-NOS (low reliability, instability through time, low acceptability), we suggest taxonomic changes in DSM-5: we introduce a new category based on three main dimensions related to socialization impairment, emotional lability and psychotic symptoms.
Our review argues for a distinction between AD and PDD-NOS on clinical characteristics and thus highlights the need to study the margins of autism. While the limitations of the PDD-NOS category made it irrelevant to investigate these margins from a research perspective, we believe that a multidimensional approach for mental health professionals taping socialization, emotion lability and psychotic symptoms would be interesting. Our review therefore encourage future studies to test relevant criteria for a new category and possibly identify developmental trajectories, specific interventions and treatments.
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