The Early Activation of Toll-Like Receptor (TLR)-3 Initiates Kidney Injury after Ischemia and Reperfusion

Acute kidney injury (AKI) is one of the most important complications in hospitalized patients and its pathomechanisms are not completely elucidated. We hypothesize that signaling via toll-like receptor (TLR)-3, a receptor that is activated upon binding of double-stranded nucleotides, might play a crucial role in the pathogenesis of AKI following ischemia and reperfusion (IR). Male adult C57Bl6 wild-type (wt) mice and TLR-3 knock-out (-/-) mice were subjected to 30 minutes bilateral selective clamping of the renal artery followed by reperfusion for 30 min 2.5h and 23.5 hours or subjected to sham procedures. TLR-3 down-stream signaling was activated already within 3 h of ischemia and reperfusion in post-ischemic kidneys of wt mice lead to impaired blood perfusion followed by a strong pro-inflammatory response with significant neutrophil invasion. In contrast, this effect was absent in TLR-3-/- mice. Moreover, the quick TLR-3 activation resulted in kidney damage that was histomorphologically associated with significantly increased apoptosis and necrosis rates in renal tubules of wt mice. This finding was confirmed by increased kidney injury marker NGAL in wt mice and a better preserved renal perfusion after IR in TLR-3-/- mice than wt mice. Overall, the absence of TLR-3 is associated with lower cumulative kidney damage and maintained renal blood perfusion within the first 24 hours of reperfusion. Thus, we conclude that TLR-3 seems to participate in the pathogenesis of early acute kidney injury.     

The discovery of new deep-sea hydrothermal vent communities in the southern ocean and implications for biogeography

Since the first discovery of deep-sea hydrothermal vents along the Galápagos Rift in 1977, numerous vent sites and endemic faunal assemblages have been found along mid-ocean ridges and back-arc basins at low to mid latitudes. These discoveries have suggested the existence of separate biogeographic provinces in the Atlantic and the North West Pacific, the existence of a province including the South West Pacific and Indian Ocean, and a separation of the North East Pacific, North East Pacific Rise, and South East Pacific Rise. The Southern Ocean is known to be a region of high deep-sea species diversity and centre of origin for the global deep-sea fauna. It has also been proposed as a gateway connecting hydrothermal vents in different oceans but is little explored because of extreme conditions. Since 2009 we have explored two segments of the East Scotia Ridge (ESR) in the Southern Ocean using a remotely operated vehicle. In each segment we located deep-sea hydrothermal vents hosting high-temperature black smokers up to 382.8°C and diffuse venting. The chemosynthetic ecosystems hosted by these vents are dominated by a new yeti crab (Kiwa n. sp.), stalked barnacles, limpets, peltospiroid gastropods, anemones, and a predatory sea star. Taxa abundant in vent ecosystems in other oceans, including polychaete worms (Siboglinidae), bathymodiolid mussels, and alvinocaridid shrimps, are absent from the ESR vents. These groups, except the Siboglinidae, possess planktotrophic larvae, rare in Antarctic marine invertebrates, suggesting that the environmental conditions of the Southern Ocean may act as a dispersal filter for vent taxa. Evidence from the distinctive fauna, the unique community structure, and multivariate analyses suggest that the Antarctic vent ecosystems represent a new vent biogeographic province. However, multivariate analyses of species present at the ESR and at other deep-sea hydrothermal vents globally indicate that vent biogeography is more complex than previously recognised.     

Hermit crabs and their symbionts: Reactions to artificially induced anoxia on a sublittoral sediment bottom

Hermit crabs play an important role in the Northern Adriatic Sea due to their abundance, wide range of symbionts, and function in structuring the benthic community. Small-scale (0.25?m(2)) hypoxia and anoxia were experimentally generated on a sublittoral soft bottom in 24?m depth in the Gulf of Trieste. This approach successfully simulates the seasonal low dissolved oxygen (DO) events here and enabled studying the behaviour and mortality of the hermit crab Paguristes eremita. The crabs exhibited a sequence of predictable stress responses and ultimately mortality, which was correlated with five oxygen thresholds. Among the crustaceans, which are a sensitive group to oxygen depletion, P. eremita is relatively tolerant. Initially, at mild hypoxia (2.0 to 1.0?ml?l(-?1) DO), hermit crabs showed avoidance by moving onto better oxygenated, elevated substrata. This was accompanied by a series of responses including decreased locomotory activity, increased body movements and extension from the shell. During a moribund phase at severe hypoxia (0.5 to 0.01?ml?l(-?1) DO), crabs were mostly immobile in overturned shells and body movements decreased. Anoxia triggered emergence from the shell, with a brief locomotion spurt of shell-less crabs. The activity pattern of normally day-active crabs was altered during hypoxia and anoxia. Atypical interspecific interactions occurred: the crab Pisidia longimana increasingly aggregated on hermit crab shells, and a hermit crab used the emerged infaunal sea urchin Schizaster canaliferus as an elevated substrate. Response patterns varied somewhat according to shell size or symbiont type (the sponge Suberites domuncula). Mortality occurred after extended anoxia (~?1.5?d) and increased hydrogen sulphide levels (H(2)S ~?128?μmol). The relative tolerance of crabs and certain symbionts (e.g. the sea anemone Calliactis parasitica) - as potential survivors and recolonizers of affected areas - may influence and promote community recovery after oxygen crises.     

Key physiological parameters dictate triggering of activity-dependent bulk endocytosis in hippocampal synapses

To maintain neurotransmission in central neurons, several mechanisms are employed to retrieve synaptically exocytosed membrane. The two major modes of synaptic vesicle (SV) retrieval are clathrin-mediated endocytosis and activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mode during intense stimulation, however the precise physiological conditions that trigger this mode are not resolved. To determine these parameters we manipulated rat hippocampal neurons using a wide spectrum of stimuli by varying both the pattern and duration of stimulation. Using live-cell fluorescence imaging and electron microscopy approaches, we established that stimulation frequency, rather than the stimulation load, was critical in the triggering of ADBE. Thus two hundred action potentials, when delivered at high frequency, were sufficient to induce near maximal bulk formation. Furthermore we observed a strong correlation between SV pool size and ability to perform ADBE. We also identified that inhibitory nerve terminals were more likely to utilize ADBE and had a larger SV recycling pool. Thus ADBE in hippocampal synaptic terminals is tightly coupled to stimulation frequency and is more likely to occur in terminals with large SV pools. These results implicate ADBE as a key modulator of both hippocampal neurotransmission and plasticity.     

Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid

ABSTRACT: BACKGROUND: Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. METHODS: Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GROalpha, MIP1alpha, MIP1beta, histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. RESULTS: None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender and age of the mothers. Significant differences were found in IL-4, IL-10, IL-12 TNF- alpha and MIP1-beta with respect to gestational age. CONCLUSIONS: Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender or maternal age, but may vary with respect to gestational age.     

Coexistence of two Cyclotella diatom species in the plankton of Lake Baikal

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The removal of stickies with modified starch and chitosan-Highly cationic and hydrophobic types compared with unmodified ones

The removal of dissolved and colloidal substances (DCS) in paper cycling water, so called stickies, with tailored natural polymers, having cationic as well as hydrophobic groups, was investigated using model suspensions made by the recycling of paper. The sticky content, characterized by the turbidity, the anionic charge, and the total organic carbon content (TOC) was increased by the addition of latex. The dynamic surface tension was established as useful tool for the characterization of the sticky content. The sticky removal using the starch derivatives (with benzyl- as well as ethyl-substituents), from very low up to high cationic charge and N-(benzyl)chitosan was compared. Depending on the properties of the derivatives two possible mechanisms can be found: "charge dominated removal" or "removal dominated by hydrophobicity." It seems that turbidity and TOC are lowered especially due to charge interaction whereas the increase of the surface tension is mainly caused by the hydrophobic character of the modified natural polymers.     

Altered Ca2+ signaling in skeletal muscle fibers of the R6/2 mouse,a model of Huntington’s disease

Huntington’s disease (HD) is caused by an expanded CAG trinucleotide repeat within the gene encoding the protein huntingtin. The resulting elongated glutamine (poly-Q) sequence of mutant huntingtin (mhtt) affects both central neurons and skeletal muscle. Recent reports suggest that ryanodine receptor–based Ca²⁺ signaling, which is crucial for skeletal muscle excitation–contraction coupling (ECC), is changed by mhtt in HD neurons. Consequently, we searched for alterations of ECC in muscle fibers of the R6/2 mouse, a mouse model of HD. We performed fluorometric recordings of action potentials (APs) and cellular Ca²⁺ transients on intact isolated toe muscle fibers (musculi interossei), and measured L-type Ca²⁺ inward currents on internally dialyzed fibers under voltage-clamp conditions. Both APs and AP-triggered Ca²⁺ transients showed slower kinetics in R6/2 fibers than in fibers from wild-type mice. Ca²⁺ removal from the myoplasm and Ca²⁺ release flux from the sarcoplasmic reticulum were characterized using a Ca²⁺ binding and transport model, which indicated a significant reduction in slow Ca²⁺ removal activity and Ca²⁺ release flux both after APs and under voltage-clamp conditions. In addition, the voltage-clamp experiments showed a highly significant decrease in L-type Ca²⁺ channel conductance. These results indicate profound changes of Ca²⁺ turnover in skeletal muscle of R6/2 mice and suggest that these changes may be associated with muscle pathology in HD.     

Randomized,Double-Blind,Placebo-Controlled Study on Decolonization Procedures for Methicillin-Resistant Staphylococcus aureus (MRSA) among HIV-Infected Adults

BackgroundHIV-infected persons have increased risk of MRSA colonization and skin and soft-tissue infections (SSTI). However, no large clinical trial has examined the utility of decolonization procedures in reducing MRSA colonization or infection among community-dwelling HIV-infected persons.Methods550 HIV-infected adults at four geographically diverse US military HIV clinics were prospectively screened for MRSA colonization at five body locations every 6 months during a 2-year period. Those colonized were randomized in a double-blind fashion to nasal mupirocin (Bactroban) twice daily and hexachlorophene (pHisoHex) soaps daily for 7 days compared to placeboes similar in appearance but without specific antibacterial activity. The primary endpoint was MRSA colonization at 6-months post-randomization; secondary endpoints were time to MRSA clearance, subsequent MRSA infections/SSTI, and predictors for MRSA clearance at the 6-month time point.ResultsForty-nine (9%) HIV-infected persons were MRSA colonized and randomized. Among those with 6-month colonization data (80% of those randomized), 67% were negative for MRSA colonization in both groups (p = 1.0). Analyses accounting for missing 6-month data showed no significant differences could have been achieved. In the multivariate adjusted models, randomization group was not associated with 6-month MRSA clearance. The median time to MRSA clearance was similar in the treatment vs. placebo groups (1.4 vs. 1.8 months, p = 0.35). There was no difference on subsequent development of MRSA infections/SSTI (p = 0.89). In a multivariable model, treatment group, demographics, and HIV-specific factors were not predictive of MRSA clearance at the 6-month time point.ConclusionA one-week decolonization procedure had no effect on MRSA colonization at the 6-month time point or subsequent infection rates among community-dwelling HIV-infected persons. More aggressive or novel interventions may be needed to reduce the burden of MRSA in this population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00631566","term_id":"NCT00631566"}}NCT00631566     

East Weddell Sea echinoids from the JR275 expedition

Information regarding the echinoids in this dataset is based on the Agassiz Trawl (AGT) and epibenthic sledge (EBS) samples collected during the British Antarctic Survey cruise JR275 on the RRS James Clark Ross in the austral summer 2012. A total of 56 (1 at the South Orkneys and 55 in the Eastern Weddell Sea) Agassiz Trawl and 18 (2 at the South Orkneys and 16 in the Eastern Weddell Sea) epibenthic sledge deployments were performed at depths ranging from ~280 to ~2060 m. This presents a unique collection for the Antarctic benthic biodiversity assessment of an important group of benthic invertebrates. In total 487 specimens belonging to six families, 15 genera, and 22 morphospecies were collected. The species richness per station varied between one and six. Total species richness represents 27% of the 82 echinoid species ever recorded in the Southern Ocean (David et al. 2005b, Pierrat et al. 2012, Saucède et al. 2014). The Cidaridae (sub-family Ctenocidarinae) and Schizasteridae are the two most speciose families in the dataset. They comprise seven and nine species respectively. This is illustrative of the overall pattern of echinoid diversity in the Southern Ocean where 65% of Antarctic species belong to the families Schizasteridae and Cidaridae (Pierrat et al. 2012).