CaMKIIalpha interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis

The success of acrosomal exocytosis, a complex process with a variety of inter-related steps, relies on the coordinated interaction of participating signaling molecules. Since the acrosome reaction resembles Ca(2+)-regulated exocytosis in neurons, we investigated whether cognate neuronal binding partners of the multi-PDZ domain protein MUPP1, which recruits molecules that control the initial tethering and/or docking between the acrosomal vesicle and the plasma membrane, are also expressed in spermatozoa, and whether they contribute to the regulation of acrosomal secretion. We observed that CaMKIIalpha colocalizes with MUPP1 in the acrosomal region of epididymal spermatozoa where the kinase selectively binds to a region encompassing PDZ domains 10-11 of MUPP1. Furthermore, we found that pre-treating mouse spermatozoa with a CaMKII inhibitor that directly blocks the catalytic region of the kinase, as well as a competitive displacement of CaMKIIalpha from PDZ domains 10-11, led to a significant increase in spontaneous acrosomal exocytosis. Since Ca(2+)-calmodulin releases CaMKIIalpha from the PDZ scaffolding protein, MUPP1 represents a central signaling platform to dynamically regulate the assembly and disassembly of binding partners pertinent to acrosomal secretion, thereby precisely adjusting an increase in Ca(2+) to synchronized fusion pore formation

Using an ecological land hierarchy to predict seasonal‐wetland abundance in upland forests

Abstract. Hierarchy theory, when applied to landscapes, predicts that broader-scale ecosystems constrain the development of finer-scale, nested ecosystems. This prediction finds application in hierarchical land classifications. Such classifications typically apply to physiognomically similar ecosystems, or ecological land units, e.g., a set of multi-scale forest ecosystems. We speculated that hierarchical constraint also controls the development of small, nested ecosystems that are structurally distinct from the constraining matrix. We tested this hypothesis using seasonal wetlands in upland forest. Specifically, we related seasonal-wetland abundance in upland forest stands to multi-scale terrestrial ecological units, as defined by hierarchical combinations of regional physiography, glacial landform, soils, and forest cover. Moreover, we determined the spatial scale of terrestrial ecological unit that is the best predictor of seasonal-wetland abundance. Our study area is mapped into a set of nested terrestrial ecological units, including two subsections (differing in physiography), four land-type associations (glacial landforms), and 11 land types (forest vegetation, soil). We used a geographic information system to determine seasonal wetland densities in 16-ha plots located within the nested terrestrial ecological units. Cumulative plot frequency distributions of wetland density did not differ between subsections; 50% of plots contained no wetlands, 38% contained 1-3 wetlands, and 12% contained Ն4 wetlands. Frequency distributions differed among land-type associations (LTA). Ninety percent of plots on a glacial lake plain contained no wetlands, compared to 63%, 42%, and 38% for outwash, end moraine, and ground moraine LTAs, respectively. Ten percent of plots on the lake plain contained 1-3 wetlands, compared to 32%, 48%, and 43% for the outwash, end moraine, and ground moraine, respectively. The remaining plots on the latter three LTAs contained Ͼ3 wetlands. Frequency distributions rarely differed among land types. Compared to occurrence, identity and scale of the ecological unit were poorer predictors of actual wetland densities. Regression tree analysis, while significant, explained only 11.6% of variation in wetland density among plots. Still, the leaves of the regression tree differed in densities primarily based on LTA. Our results demonstrate that identity of constraining upland forest ecosystem explains significant amounts of variation in seasonal wetland abundance. We identify glacial landform as the scale of ecological unit having the greatest control over seasonal wetland abundance. We focus on seasonal wetlands in forests, yet our approach should apply to other small, nested ecosystems. This approach may facilitate conservation management of small, nested ecosystems by providing likelihood estimates of occurrence within mapped terrestrial ecological units

Role of Chemosensory TRP Channels in Lung Cancer

Transient receptor potential (TRP) channels represent a large family of cation channels and many members of the TRP family have been shown to act as polymodal receptor molecules for irritative or potentially harmful substances. These chemosensory TRP channels have been extensively characterized in primary sensory and neuronal cells. However, in recent years the functional expression of these proteins in non-neuronal cells, e.g., in the epithelial lining of the respiratory tract has been confirmed. Notably, these proteins have also been described in a number of cancer types. As sensor molecules for noxious compounds, chemosensory TRP channels are involved in cell defense mechanisms and influence cell survival following exposure to toxic substances via the modulation of apoptotic signaling. Of note, a number of cytostatic drugs or drug metabolites can activate these TRP channels, which could affect the therapeutic efficacy of these cytostatics. Moreover, toxic inhalational substances with potential involvement in lung carcinogenesis are well established TRP activators. In this review, we present a synopsis of data on the expression of chemosensory TRP channels in lung cancer cells and describe TRP agonists and TRP-dependent signaling pathways with potential relevance to tumor biology. Furthermore, we discuss a possible role of TRP channels in the non-genomic, tumor-promoting effects of inhalational carcinogens such as cigarette smoke

Provision of artificial shelter on beaches is associated with improved shorebird fledging success

Artificial chick shelters might improve productivity of beach-nesting birds threatened by anthropogenic disturbance. We investigated the efficacy of three different chick shelter designs against four criteria: accessibility to chicks over time, thermal insulation, conspicuousness to beach-goers, and practicality (cost and ease of transport). One design (‘A-frame’) was selected because it offered the greatest thermal insulation, was the least conspicuous, most cost effective, and performed equally well in terms of accessibility. We deployed these artificial shelters on Hooded Plover Thinornis rubricollis territories where broods were present (n 5 11), and compared the behaviour and survival rate of chicks to that at control sites (n 5 10). We were unable to discern any difference in the behaviour of broods when artificial shelters were available. However, the survival rate of chicks to fledging was 71.8% higher where an artificial shelter was provided (n 5 21 broods). This was validated by analysing data from a larger sample of broods monitored as part of an active volunteer-based management programme; shelters conferred a 42.8%increase in survival to fledging (n 5 81 broods). Thus, artificial shelters have the potential to increase survival rates of threatened shorebird chicks, though the mechanisms through which survival is increased require further investigation

Elevated mitochondrial genome variation after 50 generations of radiation exposure in a wild rodent

Currently, the effects of chronic, continuous low dose environmental irradiation on the mitochondrial genome of resident small mammals are unknown. Using the bank vole (Myodes glareolus) as a model system, we tested the hypothesis that approximately 50 generations of exposure to the Chernobyl environment has significantly altered genetic diversity of the mitochondrial genome. Using deep sequencing, we compared mitochondrial genomes from 131 individuals from reference sites with radioactive contamination comparable to that present in northern Ukraine before the 26 April 1986 meltdown, to populations where substantial fallout was deposited following the nuclear accident. Population genetic variables revealed significant differences among populations from contaminated and uncontaminated localities. Therefore, we rejected the null hypothesis of no significant genetic effect from 50 generations of exposure to the environment created by the Chernobyl meltdown. Samples from contaminated localities exhibited significantly higher numbers of haplotypes and polymorphic loci, elevated genetic diversity, and a significantly higher average number of substitutions per site across mitochondrial gene regions. Observed genetic variation was dominated by synonymous mutations, which may indicate a history of purify selection against nonsynonymous or insertion/deletion mutations. These significant differences were not attributable to sample size artifacts. The observed increase in mitochondrial genomic diversity in voles from radioactive sites is consistent with the possibility that chronic, continuous irradiation resulting from the Chernobyl disaster has produced an accelerated mutation rate in this species over the last 25 years. Our results, being the first to demonstrate this phenomenon in a wild mammalian species, are important for understanding genetic consequences of exposure to low-dose radiation sources

Case report: Central venous catheter thrombosis complicated by chronic thromboembolic disease/pulmonary hypertension in two children requiring parenteral nutrition

Chronic thromboembolic pulmonary hypertension is a rare but life-threatening complication of long-term central venous catheters (CVC) in children. However, evidence in terms of potential treatment strategies and outcome data remains scarce. We describe two cases of CVC-related thrombosis (Hickman-catheter) complicated by recurrent pulmonary emboli. One patient experienced a complete thromboembolic obstruction of the right pulmonary artery with normal pulmonary pressures and the second patient suffered from a central thromboembolic obstruction of both pulmonary arteries associated with severe pulmonary hypertension. Both patients successfully underwent surgical thromboendarterectomy with deep hypothermic circulatory arrest

Baseline risk factors of in-hospital mortality after surgery for acute type A aortic dissection: an ERTAAD study

Background Surgery for type A aortic dissection (TAAD) is associated with high risk of mortality. Current risk scoring methods have a limited predictive accuracy.Methods Subjects were patients who underwent surgery for acute TAAD at 18 European centers of cardiac surgery from the European Registry of Type A Aortic Dissection (ERTAAD).Results Out of 3,902 patients included in the ERTAAD, 2,477 fulfilled the inclusion criteria. In the validation dataset (2,229 patients), the rate of in-hospital mortality was 18.4%. The rate of composite outcome (in-hospital death, stroke/global ischemia, dialysis, and/or acute heart failure) was 41.2%, and 10-year mortality rate was 47.0%. Logistic regression identified the following patient-related variables associated with an increased risk of in-hospital mortality [area under the curve (AUC), 0.755, 95% confidence interval (CI), 0.729-0.780; Brier score 0.128]: age; estimated glomerular filtration rate; arterial lactate; iatrogenic dissection; left ventricular ejection fraction <= 50%; invasive mechanical ventilation; cardiopulmonary resuscitation immediately before surgery; and cerebral, mesenteric, and peripheral malperfusion. The estimated risk score was associated with an increased risk of composite outcome (AUC, 0.689, 95% CI, 0.667-0.711) and of late mortality [hazard ratio (HR), 1.035, 95% CI, 1.031-1.038; Harrell's C 0.702; Somer's D 0.403]. In the validation dataset (248 patients), the in-hospital mortality rate was 16.1%, the composite outcome rate was 41.5%, and the 10-year mortality rate was 49.1%. The estimated risk score was predictive of in-hospital mortality (AUC, 0.703, 95% CI, 0.613-0.793; Brier score 0.121; slope 0.905) and of composite outcome (AUC, 0.682, 95% CI, 0.614-0.749). The estimated risk score was predictive of late mortality (HR, 1.035, 95% CI, 1.031-1.038; Harrell's C 0.702; Somer's D 0.403), also when hospital deaths were excluded from the analysis (HR, 1.024, 95% CI, 1.018-1.031; Harrell's C 0.630; Somer's D 0.261).Conclusions The present analysis identified several baseline clinical risk factors, along with preoperative estimated glomerular filtration rate and arterial lactate, which are predictive of in-hospital mortality and major postoperative adverse events after surgical repair of acute TAAD. These risk factors may be valuable components for risk adjustment in the evaluation of surgical and anesthesiological strategies aiming to improve the results of surgery for TAAD.Clinical Trial Registration https://clinicaltrials.gov, identifier NCT04831073