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To achieve sustainable shark fisheries, it is key to understand not only the biological drivers and environmental consequences of overfishing, but also the social and economic drivers of fisher behavior. The extinction risk of sharks is highest in coastal tropical waters, where small‐scale fisheries are most prevalent. Small‐scale fisheries provide a critical source of economic and nutritional security to coastal communities, and these fishers are among the most vulnerable social and economic groups. We used Kenya's and Zanzibar's small‐scale shark fisheries, which are illustrative of the many data‐poor, small‐scale shark fisheries worldwide, as case studies to explore the relationship between extinction risk and the economic and nutritional value of sharks. To achieve this, we combined existing data on shark landings, extinction risk, and nutritional value with sales data at 16 key landing sites and information from interviews with 476 fishers. Shark fisheries were an important source of economic and nutritional security, valued at >US$4 million annually and providing enough nutrition for tens of thousands of people. Economically and nutritionally, catches were dominated by threatened species (72.7% and 64.6–89.7%, respectively). The most economically valuable species were large and slow to reproduce (e.g. mobulid rays, wedgefish, and bull, silky, and mako sharks) and therefore more likely to be threatened with extinction. Given the financial incentive and intensive fishing pressure, small‐scale fisheries are undoubtedly major contributors to the decline of threatened coastal shark species. In the absence of effective fisheries management and enforcement, we argue that within small‐scale fisheries the conditions exist for an economically incentivized feedback loop in which vulnerable fishers are driven to persistently overfish vulnerable and declining shark species. To protect these species from extinction, this feedback loop must be broken. [ABSTRACT FROM AUTHOR]

Populations of Indo-Pacific bottlenose dolphin (Tursiops aduncus) are distributed along coastal regions of the south-west Indian Ocean (SWIO), from South Africa to Kenya. An account of whistles from wild T. aduncus inhabiting the SWIO is provided here. Recordings were made at Plettenberg Bay (South Africa) and Zanzibar Island (Tanzania) and the frequency trace of whistle contours (n = 1677) was extracted. Multiple parameters were measured from each whistle and compared between regions and encounters. Regional variation was significant in all parameters assessed except for start and middle frequency (frequency at half the duration). Whistles from Zanzibar Island ended on average 4 kHz higher than those from Plettenberg Bay, and had a steeper frequency gradient. However, mean frequencies differed by <1 kHz and population averages for the adopted frequency distribution showed similar patterns, with a peak between 5 and 7 kHz. Whistle parameters were strongly influenced by recording encounter, likely reflecting the presence of different individuals, group compositions and behavioral contexts during recording occasions. Comparisons within the genus showed that T. aduncus from the SWIO have amongst the lowest start and minimum frequency of whistles within Tursiops. [ABSTRACT FROM AUTHOR]

The article focuses on the records of marine mammals in Tanzania undertaken by the Marine Mammal Education and Research Group of the Institute of Marine Sciences in Roatan, Honduras in 1998. It mentions that most of the information on marine mammals was collected off the coast of Unguja Island and data gathering is undertaken through sampling procedure of strandings and bycatch marine mammals. The results show that from 1992 to 2008, 22 marine mammals were reported stranded. Moreover, the results also show that from January 2000 to December 2008, 213 bycatches and one dugong were reported.

The β-cell is equipped with at least six voltage-gated Ca2+ (Cav) channel α1-subunits designated Cav1.2, Cav1.3, Cav2.1, Cav2.2, Cav2.3, and Cav3.1. These principal subunits, together with certain auxiliary subunits, assemble into different types of Cav channels conducting L-, P/Q-, N-, R-, and T-type Ca2+ currents, respectively. The β cell shares customary mechanisms of Cav channel regulation with other excitable cells, such as protein phosphorylation, Ca2+-dependent inactivation, and G protein modulation How ever, the β-cell displays some characteristic features to bring these mechanisms into play. In islet β-cells. Cav channels can be highly phosphorylated under basal conditions and thus marginally respond to further phosphorylation. In β-cell lines, Cav channels can be surrounded by tonically activated protein phosphatases dominating over protein kinases; thus their activity is dramatically enhanced by inhibition of protein phosphatases. During the last 10 years, we have revealed some novel mechanisms of β-cell Cav channel regulation under physiological and pathophysiological conditions, including the involvement of exocytotic proteins, inositol hexakisphosphate, and type 1 diabetic serum. This minireview highlights characteristic features of customary mechanisms of Cav channel regulation in β-cells and also reviews our studies on newly identified mechanisms of β-cell Cav channel regulation. [ABSTRACT FROM AUTHOR]

In this issue of the JCI, Ciampi et at. report the identification of a novel oncogene in patients affected by radiation-associated thyroid papillary carcinomas (see the related article beginning on page 94). This oncogene derives from a paracentric inversion of the long arm of chromosome 7, which results in an in-frame fusion of the N-terminus of the A-kinase anchor protein 9 (AKAP9) gene with the C-terminal catalytic domain (exons 9-18) of the serine-threonine kinase BRAF. The resulting AKAP9-BRAF fusion protein shows constitutive kinase activity, and it is able to transmit mitogenic signals to the MAPK pathways and to promote malignant transformation of NIH3T3 cells. [ABSTRACT FROM AUTHOR]

An oscillatory increase in pancreatic β cell cytoplasmic free Ca2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel β3 subunit in the molecular regulation of these [Ca2+]i oscillations has now been clarified by using β3 subunit-deficient β cells. β3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in β cells lacking the β3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the β3 subunit negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the β3 subunit in the β cell may constitute the basis for a novel diabetes therapy. [Copyright &y& Elsevier]

Inositolhexakisphosphate (InsP[sub 6]) plays a pivotal role in the pancreatic β-cell stimulus-secretion coupling. We have used capacitance measurements to study the effects of InsP[sub 6] on ca[sup 2+]-dependent exocytosis in single mouse pancreatic β-cells. In the presence of inhibitors of the protein phosphatase calcineurin to block endocytosis, intracellular application of InsP[sub 6] produced a dosedependent stimulation of exocytosis, and half-maximal effect was observed at 22 μM. The stimulatory effect of InsP[sub 6] was dependent on protein kinase C (PKC) activity. Antisense oligonucleotides directed against specific PKC isoforms (α, βII, δ, ∈, ξ) revealed the involvement of PKC-∈ in InsP[sub 6]-induced exocytosis. Furthermore, expression of dominant negative PKC-∈ abolished InsP[sub 6]evoked exocytosis, whereas expression of wild-type PKC-∈ led to a significant stimulation of InsP[sub 6]-induced exocytosis. These data demonstrate that PKC-∈ is involved in InsP[sub 6]-induced exocytosis in pancreatic β-cells. [ABSTRACT FROM AUTHOR]

A field experiment with Dukane NetMark™ 1000 pingers was conducted in the bottom-set gillnet fishery for cod in the Swedish Skagerrak Sea between March and April 1997. The aim of the experiment was to evaluate (i) the effectiveness of pingers to reduce by-catch rate of harbour porpoises, and (ii) the effects of pingers on the catches of the target species in the fishery. The design of the study was based on a statistical power analysis and the results from observer programmes conducted 1995–1996 in the same area, fishery and time of year.The catches of cod, pollack and other fish species were not affected by the sound of the pingers in the active strings. No harbour porpoise was caught in any control or active string, which was a significantly lower by-catch rate than in the two previous years. This could not be explained by a reduction in fishing effort per se, a difference in the total catch of fish for consumption or a shift in the spatial distribution of the sets between the observer programmes and the pinger experiment. However, the spatial analyses demonstrated that the experimental strings were set parallel to the coast and along the 50 m isobath, and that the audible range of the active pingers on average covered 16% of the longitudinal length and 5% of the surface area of the experimental fishing area. A compilation of herring landings by Swedish fishermen operating in the Skagerrak Sea 1995–1997 suggests that herring were more abundant in 1997 than in 1995. Good access to food in other parts of the porpoises'' distribution range and an aversive reaction to the ensonification could have caused their displacement in the fishing area.A displacement effect by pingers is likely to be more prominent in coastal waters where access to bodies of water is limited and the consequence may be serious if the area is critical to the survival of the porpoise population. Copyright 2002 International Council for the Exploration of the Sea. Published by Elsevier Science Ltd. All rights reserved. [Copyright &y& Elsevier]

Mitochondrial dynamics and bioenergetics are central to glucose-stimulated insulin secretion by pancreatic beta cells. Previously, we demonstrated that a disturbance in glucose-invoked fission impairs insulin secretion by compromising glucose catabolism. Here, we investigated whether the overexpression of mitochondrial fission regulator Drp1 in MIN6 cells can improve or rescue insulin secretion. Although Drp1 overexpression slightly improves the triggering mechanism of insulin secretion of the Drp1-knockdown cells and has no adverse effects on mitochondrial metabolism in wildtype MIN6 cells, the constitutive presence of Drp1 unexpectedly impairs insulin content, which leads to a reduction in the absolute values of secreted insulin. Coherent with previous studies in Drp1-overexpressing muscle cells, we found that the upregulation of ER stress-related genes (BiP, Chop, and Hsp60) possibly impacts insulin production in MIN6 cells. Collectively, we confirm the important role of Drp1 for the energy-coupling of insulin secretion but unravel off-targets effects by Drp1 overexpression on insulin content that warrant caution when manipulating Drp1 in disease therapy. [ABSTRACT FROM AUTHOR]

The authors focus on a study published in journal "Nature Medicine" related to noninvasively control of gene expression by the application of radiogenetics and magnetic field in mice. Topics discussed include use of nanoparticle to control transgene expression and glucose homeostasis in a diabetic mouse, activation of tethered TRPV1Ca2+ channel by iron nanoparticles through radio waves or magnetic field and conversion of oscillatory magnetic field in oscillatory pattern.

It is well known that type-2 diabetes mellitus (T2D) is increasing worldwide, but also the autoimmune form, type-1 diabetes (T1D), is affecting more people. The latest estimation from the International Diabetes Federation (IDF) is that 1.1 million children and adolescents below 20 years of age have T1D. At present, we have no primary, secondary or tertiary prevention or treatment available, although many efforts testing different strategies have been made. This review is based on the findings that apolipoprotein CIII (apoCIII) is increased in T1D and that in vitro studies revealed that healthy β-cells exposed to apoCIII became apoptotic, together with the observation that humans with higher levels of the apolipoprotein, due to mutations in the gene, are more susceptible to developing T1D. We have summarized what is known about apoCIII in relation to inflammation and autoimmunity in in vitro and in vivo studies of T1D. The aim is to highlight the need for exploring this field as we still are only seeing the top of the iceberg. [ABSTRACT FROM AUTHOR]

The article reports on the link of Sirt1, an enzyme having the capacity to remove acetyl groups from specific nuclear proteins, to the regulation of aging. The enzyme is able to control glucose metabolism by serving as a sensor of the metabolic status in the hepatocytes. It regulates the activity of a variety of transcription factors and transcriptional coregulators. Sirt1 modulates aging and may consequently serve as a key decoder that translates caloric restriction to increase lifespan.

In an open letter published in 2002 in the "New York Times", 21 distinguished scientists criticized Japan's program of scientific research whaling, noting its poor design and unjustified reliance upon lethal sampling. In a Forum article in "BioScience," Aron, Burke, and Freeman castigate the letter's signers and accuse them of meddling in political issues without sufficient knowledge of the science involved in those issues. As members of the Scientific Committee (SC) of the International Whaling Commission (IWC), we can attest that the signers of the open letter correctly summarized criticisms made by researchers very familiar with Japanese scientific whaling. One such critique was presented and discussed last year at a meeting of the SC. It was authored by SC members representing a broad range of countries, yet mention of this paper and others like it was absent from Aron and his colleagues' commentary, betraying a selectiveness that pervades their article. The authors quote lines from SC reports to support their contention that the IWC regards scientific whaling as valuable, but they fail to acknowledge many other sections that are highly critical of the Japanese program. Japan's scientific whaling program in the North Pacific (JARPN) was originally described as a feasibility study, but it included no performance measures by which to judge its success or failure. Fundamental problems of the JARPN II study include a lack of testable hypotheses or performance measures; inappropriate use of ecosystem models and failure to include sensitivity analyses and key data on other ecosystem components; selective or inappropriate use of data or methods in estimating whale abundance; unnecessary reliance on lethal sampling; inappropriate geographic sampling for population structure analysis; and unrealistic assessments of the effect of the proposed catches on the populations concerned.

Multiple inositol polyphosphate phosphatase (MINPP1) is an enigmatic enzyme that is responsible for the metabolism of inositol hexakisphosphate (InsP6) and inositol 1,3,4,5,6 pentakisphosphate (Ins(1,3,4,5,6)P5 in mammalian cells, despite being restricted to the confines of the ER. The reason for this compartmentalization is unclear. In our previous studies in the insulin-secreting HIT cell line, we expressed MINPP1 in the cytosol to artificially reduce the concentration of these higher inositol phosphates. Undocumented at the time, we noted cytosolic MINPP1 expression reduced cell growth. We were struck by the similarities in substrate preference between a number of different enzymes that are able to metabolize both inositol phosphates and lipids, notably IPMK and PTEN. MINPP1 was first characterized as a phosphatase that could remove the 3-phosphate from inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4). This molecule shares strong structural homology with the major product of the growth-promoting Phosphatidyl 3-kinase (PI3K), phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and PTEN can degrade both this lipid and Ins(1,3,4,5)P4. Because of this similar substrate preference, we postulated that the cytosolic version of MINPP1 (cyt-MINPP1) may not only attack inositol polyphosphates but also PtdIns(3,4,5)P3, a key signal in mitogenesis. Our experiments show that expression of cyt-MINPP1 in HIT cells lowers the concentration of PtdIns(3,4,5)P3. We conclude this reflects a direct effect of MINPP1 upon the lipid because cyt-MINPP1 actively dephosphorylates synthetic, di(C4:0)PtdIns(3,4,5)P3 in vitro. These data illustrate the importance of MINPP1′s confinement to the ER whereby important aspects of inositol phosphate metabolism and inositol lipid signaling can be separately regulated and give one important clarification for MINPP1′s ER seclusion. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) imaging and ultrasound experimental measurements were combined to reconstruct the acoustic properties (density, velocity, and impedance) of the head from a deceased Indo-Pacific humpback dolphin (Sousa chinensis). The authors extracted 42 soft forehead tissue samples to estimate the sound velocity and density properties at room temperature, 25.0  °C. Hounsfield Units (HUs) of the samples were read from CT scans. Linear relationships between the tissues' HUs and velocity, and HUs and density were revealed through regression analyses. The distributions of the head acoustic properties at axial, coronal, and sagittal cross sections were reconstructed, suggesting that the forehead soft tissues were characterized by low-velocity in the melon, high-velocity in the muscle and connective tissues. Further, the sound velocities of melon, muscle, and connective tissue pieces were measured under different temperatures to investigate tissues' velocity response to temperature. The results demonstrated nonlinear relationships between tissues' sound velocity and temperature. This study represents a first attempt to provide general information on acoustic properties of this species. The results could provide meaningful information for understanding the species' bioacoustic characteristics and for further investigation on sound beam formation of the dolphin. [ABSTRACT FROM AUTHOR]

Obligate coral feeders such as many members of the Chaetodontidae family (also known as butterflyfish) often show strong preferences for particular coral species. This is thought to have evolved through natural selection as an energy-maximising strategy. Although some species remain as highly specialised feeders throughout their lifetime, many corallivores show a degree of dietary versatility when food abundance is limited; a strategy described by the optimal foraging theory. This study aimed to examine if, within-reef differences in the feeding regime and territory size of the Triangle Butterflyfish Chaetodon triangulum occurred, as a function of resource availability. Results showed that the dietary specialisation of C. triangulum was significant in both areas of low and high coral cover (χL22 = 2.52 x 102, P<0.001 and χL22 = 3.78 x 102, P<0.001 respectively). Resource selection functions (RSFs), calculated for the two main sites of contrasting coral assemblage, showed that in the resource-rich environments, only two Genera (Acropora and Pocillopora) were preferentially selected for, with the majority of other corals being actively ‘avoided’. Conversely, in territories of lower coral coverage, C. triangulum was being less selective in its prey choice and consuming corals in a more even distribution with respect to their availability. Interestingly, coral cover appeared to show no significant effect on feeding rate, however it was a primary determinant of territory size. The findings of the study agree with the predictions of the optimal foraging theory, in that where food supply is scarce, dietary specialisation is minimised and territory size increased. This results in maximising energy intake. This study represents the first scientific evidence that C. triangulum is an obligate corallivore and, as with many other butterflyfish, is therefore dependent on healthy scleractinian corals for survival. [ABSTRACT FROM AUTHOR]

Endocytosis is controlled by a well-orchestrated molecular machinery, where the individual players as well as their precise interactions are not fully understood. We now show that syndapin I/PACSIN 1 is expressed in pancreatic β cells and that its knockdown abrogates β cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca2+ channels. Intriguingly, inositol hexakisphosphate (InsP6) activates casein kinase 2 (CK2) that phosphorylates syndapin I/PACSIN 1, thereby promoting interactions between syndapin I/PACSIN 1 and neural Wiskott–Aldrich syndrome protein (N-WASP) and driving β cell endocytosis. Dominant-negative interference with endogenous syndapin I/PACSIN 1 protein complexes, by overexpression of the syndapin I/PACSIN 1 SH3 domain, decreases InsP6-stimulated endocytosis. InsP6 thus promotes syndapin I/PACSIN 1 priming by CK2-dependent phosphorylation, which endows the syndapin I/PACSIN 1 SH3 domain with the capability to interact with the endocytic machinery and thereby initiate endocytosis, as exemplified in β cells. [ABSTRACT FROM AUTHOR]

Western-type diets are linked to obesity and diabetes partly because of their high-saturated fatty acid (SFA) content. We found that SFAs, but not unsaturated fatty acids (USFAs), reduced lipid droplets (LDs) within pancreatic ß cells. Mechanistically, SFAs, but not USFAs, reduced LD formation by inducing S-acylation and proteasomal, mediated degradation of fat storage-inducing transmembrane protein 2 (FIT2), an endoplasmic reticulum (ER) resident protein important for LD formation. Targeted ablation of FIT2 reduced ß cell LD numbers, lowered ß cell ATP levels, reduced Ca2+ signaling, dampened vesicle exocytosis, down-regulated ß cell transcription factors, up-regulated unfolded protein response genes, and finally, exacerbated diet-induced diabetes in mice. Subsequent mass spectrometry studies revealed increased C16:0 ceramide accumulation in islets of diet-induced diabetes mice lacking ß cell FIT2. Inhibition of ceramide synthases ameliorated the enhanced ER stress and improved insulin secretion. FIT2 was reduced in mouse diabetic islets, and separately, overexpression of FIT2 increased the number of intracellular LDs and rescued SFA-induced ER stress and apoptosis, thereby highlighting the protective role of FIT2 and LDs against ß cell lipotoxicity. [ABSTRACT FROM AUTHOR]

Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes' size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII. [ABSTRACT FROM AUTHOR]

ATP-sensitive K+ (KATP) channels couple cellular metabolism to electrical activity in many cell types. Wild-type KATP channels are comprised of four pore forming (Kir6.x) and four regulatory (sulfonylurea receptor, SURx) subunits that each contain RKR endoplasmic reticulum retention sequences that serve to properly translocate the channel to the plasma membrane. Truncated Kir6.x variants lacking RKR sequences facilitate plasma membrane expression of functional Kir6.x in the absence of SURx; however, the effects of channel truncation on plasma membrane orientation have not been explored. To investigate the role of truncation on plasma membrane orientation of ATP sensitive K+ channels, three truncated variants of Kir6.2 were used (Kir6.2ΔC26, 6xHis-Kir6.2ΔC26, and 6xHis-EGFP-Kir6.2ΔC26). Oocyte expression of Kir6.2ΔC26 shows the presence of a population of inverted inserted channels in the plasma membrane, which is not present when co-expressed with SUR1. Immunocytochemical staining of intact and permeabilized HEK293 cells revealed that the N-terminus of 6xHis-Kir6.2ΔC26 was accessible on both sides of the plasma membrane at roughly equivalent ratios, whereas the N-terminus of 6xHis-EGFP-Kir6.2Δ26 was only accessible on the intracellular face. In HEK293 cells, whole-cell electrophysiological recordings showed a ca. 50% reduction in K+ current upon addition of ATP to the extracellular solution for 6xHis-Kir6.2ΔC26, though sensitivity to extracellular ATP was not observed in 6xHis-EGFP-Kir6.2ΔC26. Importantly, the population of channels that is inverted exhibited similar function to properly inserted channels within the plasma membrane. Taken together, these data suggest that in the absence of SURx, inverted channels can be formed from truncated Kir6.x subunits that are functionally active which may provide a new model for testing pharmacological modulators of Kir6.x, but also indicates the need for added caution when using truncated Kir6.2 mutants. [ABSTRACT FROM AUTHOR]

Sveegaard, S., Teilmann, J., Berggren, P., Mouritsen, K. N., Gillespie, D., and Tougaard, J. 2011. Acoustic surveys confirm the high-density areas of harbour porpoises found by satellite tracking. – ICES Journal of Marine Science, 68: 929–936.The population status of the harbour porpoise (Phocoena phocoena) has long been of concern in European waters. Consequently, the European Commission (EC) Habitats Directive obligates all EC member states to designate marine protected areas (MPAs) for harbour porpoises before 2012. These will be designated areas having the greatest density of porpoises. However, little is known about comparability between the monitoring methods used to examine porpoise distribution and density, and conflicting results may arise, especially when considering their varying sample size and temporal and spatial scales. Here, vessel-based acoustic surveys are seen as an independent method of testing the temporal and spatial permanence of previously identified areas of high density of harbour porpoises found by satellite-tracking them in inner Danish waters. Based on six acoustic surveys, a strong spatial accord was found between the number of acoustic detections of harbour porpoises and their density distribution obtained from 10 years of satellite tracking. The results confirm the presence and permanence of areas of high density of porpoises and validate the two methods for identifying and monitoring future MPAs for the species. [ABSTRACT FROM PUBLISHER]

Hypoglycemic sulfonylureas such as glibenclamide have been widely used to treat type 2 diabetic patients for 40 yr, but controversy remains about their mode of action. The widely held view is that they promote rapid insulin exocytosis by binding to and blocking pancreatic β-cell ATP-dependent K[sup +] (K[sub ATP]) channels in the plasma membrane. This event stimulates Ca[sup 2+] influx and sets in motion the exocytotic release of insulin. However, recent reports show that >90% of glibenclamide-binding sites are localized intracellularly and that the drug can stimulate insulin release independently of changes in K[sub ATP] channels and cytoplasmic free Ca[sup 2+]. Also, glibenclamide specifically and progressively accumulates in islets in association with secretory granules and mitochondria and causes long-lasting insulin secretion. It has been proposed that nutrient insulin secretagogues stimulate insulin release by increasing formation of malonyl-CoA, which, by blocking carnitine palmitoyltransferase 1 (CPT-1), switches fatty acid (FA) catabolism to synthesis of PKC-activating lipids. We show that glibenclamide dose-dependently inhibits β-cell CPT-1 activity, consequently suppressing FA oxidation to the same extent as glucose in cultured fetal rat islets. This is associated with enhanced diacylglycerol (DAG) formation, PKC activation, and K[sub ATP]-independent glibenclamide-stimulated insulin exocytosis. The fat oxidation inhibitor etomoxir stimulated K[sub ATP]-independent insulin secretion to the same extent as glibenclamide, and the action of both drugs was not additive. We propose a mechanism in which inhibition of CPT-1 activity by glibenclamide switches β-cell FA metabolism to DAG synthesis and subsequent PKC-dependent and K[sub ATP]-independent insulin exocytosis. We suggest that chronic CPT inhibition, through the progressive islet accumulation of glibenclamide, may explain the prolonged stimulation of insulin secretion in some diabetic... [ABSTRACT FROM AUTHOR]

Pancreatic β-cell function is essential for the regulation of glucose homeostasis and its impairment leads to diabetes mellitus. Besides glucose, the major nutrient factor, inputs from neural and humoral components and intraislet cell–cell communication act together to guarantee an appropriate pancreatic β-cell function. Data obtained over the last 5 years in several laboratories have revitalized a controversial concept, namely the autocrine feedback action of secreted insulin on β-cell function. While, historically, insulin was suggested to exert a negative effect on β-cells, recent data provide evidence for a positive role of insulin in transcription, translation, ion flux, insulin secretion and β-cell survival. [Copyright &y& Elsevier]

The imidazoline RX871024 increased basal- and glucose-stimulated insulin release in vitro and in vivo. The compound inhibited activity of ATP-sensitive K(+) channels as well as voltage-gated K(+) channels, which led to membrane depolarization, an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)), and insulin release. Importantly, RX871024 also enhanced the insulinotropic effect of glucose in cells with clamped [Ca(2+)](i) but in the presence of high ATP and Ca(2+)concentration inside the cell. We believe that the latter effect on insulin exocytosis was at least in part mediated by a rise in diacylglycerol, which then activated protein kinase C (PKC) and increased the generation of arachidonic acid (AA) metabolites. Activation of both the PKC and AA pathways resulted in potentiation of glucose effects on insulin secretion. Unlike RX871024, the novel imidazoline BL11282 did not block ATP-dependent K(+) channels, but similarly to RX871024, it stimulated insulin secretion in depolarized or permeabilized islets. Accordingly, BL11282 did not influence glucose and insulin levels under basal conditions either in vitro or in vivo, but it markedly enhanced the insulinotropic effects of glucose. BL11282 restored the impaired insulin response to glucose in islets from spontaneously diabetic GK rats. We conclude that BL11282 belongs to a new class of insulinotropic compounds that demonstrate a strong glucose-dependent effect on insulin exocytosis. [ABSTRACT FROM AUTHOR]

Fluorescent proteins have been extensively used as protein "tags" to study the subcellular localization of proteins and/or their translocation upon stimulation or as markers for transfection in transient and stable expression systems. However, they have not been frequently used as reporter genes to monitor stimulus-induced gene expression in mammalian cells. Here we demonstrate the use of fluorescent proteins to study stimulus-induced gene transcription. The general applicability of the approach is exemplified by doxycyclin-(Tet-On) and phorbol 12-myristate 13-acetate-induced (c-fos) promoter activation, with green fluorescent protein (GFP) and red fluorescent protein (DsRed) as semiquantitative and immediate reporters, of transcription activation. Under the control of beta-cell-specific promoters, such as the rat insulin 1 promoter or the rat upstream glucokinase promoter, this approach allowed us to monitor online glucose-induced gene transcription in primary beta-cells at the single-cell level as well as in the context of the islet of Langerhans. Applying discretely detectable fluorescent proteins, for example GFP and DsRed, enabled us to simultaneously monitor stimulus-induced transcription by two different promoters in the same cell. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of surfactant and specific antibody on bacterial proliferation in experimental pneumococcal pneumonia. Methods: Near-term newborn rabbits received a standard dose (10[sup 7]) of type 3 pneumococci via the airways. Control animals were sacrificed 1 minute later. Other animals were ventilated for 5 hours and treated via the tracheal cannula with surfactant (Curosurf 200 mg/kg), a mixture of surfactant and a polyclonal antipneumococcal antibody, the antibody without surfactant, or saline. Results: There was a significant bacterial proliferation in lung tissue in all animals ventilated for 5 hours. Bacterial growth, expressed as log[sub 10] colony forming units (CFU) per gram of lung tissue was less prominent in animals treated with a mixture of surfactant and specific antibody than in animals treated with antibody alone (median, 7.51, range, 6.80-7.70 vs. median, 7.92, range, 7.07-8.50; P < 0.05). Dynamic lung-thorax compliance was improved with surfactant or surfactant plus anti-body in comparison with saline or antibody alone. Conclusion: The data suggest that the suppressive effect of the antibody on bacterial proliferation becomes evident only when surfactant is administered together with the antibody. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol 4,5-bisphosphate (PIP2) has been suggested to play an important role as an endogenous regulator of ATP-sensitive potassium (KATP) channels consisting of Kir6.2 as a pore-forming subunit. These studies show the ability of PIP2 to activate KATP channel activity and to counteract the inhibitory effect of ATP, implying that PIP2 could serve the function of modulating the sensitivity of KATP channels to the cytoplasmic free ATP concentration. Careful examination of the literature reveals that the definitive physiologically relevant experiments to establish efficacy of PIP2 on this channel may still have to be performed. Our reservations are based on the handling of PIP2 in cell-free experiments and in various strategies designed to modulate PIP2 concentrations in intact cells. Furthermore, a potent stimulatory effect of phosphatidylinositol 3,4,5trisphosphate, a downstream metabolite of PIP2, on KATP channel activity raises the possibility that the effects on the KATP channel may not be directly related to PIP2. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated whether lowering or preventing high-fat diet (HFD)-induced increased in apolipoprotein CIII (apoCIII) protects against the detrimental metabolic consequences. Topics discussed include reason that prolonged ASO treatment reversed the metabolic phenotype, liver function in antisepses oligonucleotide (ASO)-treated mice on HFD, and size exclusion chromatography analysis.

Odontocetes produce ultrasonic clicks for navigation and foraging. These are commonly categorized as regular or buzz clicks based on the inter-click interval. Buzz clicks are linked to foraging behaviors and may be subdivided into slow buzz clicks for prey chase, and regular buzz clicks for prey capture. This study recorded these three click types produced by white-beaked dolphins (Lagenorhynchus albirostris) off the Northumberland coast, UK. Acoustic parameters (including duration, centroid frequency, and root-mean-squared bandwidth) were calculated and compared across the three click types. The results showed that the regular clicks had shorter durations and higher frequencies than both the buzz click types. The regular buzz clicks had longer durations, lower frequencies, and narrower bandwidths than the slow buzz clicks. Additionally, regardless of click type, about 30% of the clicks had high-frequency (200–250 kHz) secondary peaks and >90% of the clicks displayed spectral peak and notch patterns between 20 and 80 kHz. These findings are useful for future quantitative assessment of the echolocation performance of white-beaked dolphins in the wild. The patterns of spectral peaks and notches identified may facilitate for acoustic identification of this species. [ABSTRACT FROM AUTHOR]

Glucose-stimulated insulin secretion is the hallmark of the pancreatic β-cell, a critical player in the regulation of blood glucose concentration. In 1974, the remarkable observation was made that an efflux of intracellular inorganic phosphate (Pi) accompanied the events of stimulated insulin secretion. The mechanism behind this "phosphate flush," its association with insulin secretion, and its regulation have since then remained a mystery. We recapitulated the phosphate flush in the MIN6m9 β-cell line and pseudoislets. We demonstrated that knockdown of XPR1, a phosphate transporter present in MIN6m9 cells and pancreatic islets, prevented this flush. Concomitantly, XPR1 silencing led to intracellular Pi accumulation and a potential impact on Ca2+ signaling. XPR1 knockdown slightly blunted first-phase glucose-stimulated insulin secretion in MIN6m9 cells, but had no significant impact on pseudoislet secretion. In keeping with other cell types, basal Pi efflux was stimulated by inositol pyrophosphates, and basal intracellular Pi accumulated following knockdown of inositol hexakisphosphate kinases. However, the glucose-driven phosphate flush occurred despite inositol pyrophosphate depletion. Finally, while it is unlikely that XPR1 directly affects exocytosis, it may protect Ca2+ signaling. Thus, we have revealed XPR1 as the missing mediator of the phosphate flush, shedding light on a 45-year-old mystery. [ABSTRACT FROM AUTHOR]

Islet vascularization is essential for intact islet function and glucose homeostasis. We have previously shown that primary cilia directly regulate insulin secretion. However, it remains unclear whether they are also implicated in islet vascularization. At eight weeks, murine Bbs4-/-islets show significantly lower intra-islet capillary density with enlarged diameters. Transplanted Bbs4-/-islets exhibit delayed re-vascularization and reduced vascular fenestration after engraftment, partially impairing vascular permeability and glucose delivery to b-cells. We identified primary cilia on endothelial cells as the underlying cause of this regulation, via the vascular endothelial growth factor-A (VEGF-A)/VEGF receptor 2 (VEGFR2) pathway. In vitro silencing of ciliary genes in endothelial cells disrupts VEGF-A/VEGFR2 internalization and downstream signaling. Consequently, key features of angiogenesis including proliferation and migration are attenuated in human BBS4 silenced endothelial cells. We conclude that endothelial cell primary cilia regulate islet vascularization and vascular barrier function via the VEGF-A/VEGFR2 signaling pathway. [ABSTRACT FROM AUTHOR]

The secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: (1) do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and (2) is glucokinase the alpha cell glucose sensor in this scenario. Single cell RT-PCR was used to confirm that glucokinase is the main glucose-phosphorylating enzyme expressed in rat pancreatic alpha cells. Modulation of glucokinase activity by pharmacological activators and inhibitors led to a lowering or an increase of the glucose threshold of glucagon release from single alpha cells, measured by TIRF microscopy, respectively. Knockdown of glucokinase expression resulted in a loss of glucose control of glucagon secretion. Taken together this study provides evidence for a crucial role of glucokinase in intrinsic glucose regulation of glucagon release in rat alpha cells. [ABSTRACT FROM AUTHOR]

Recent sampling efforts in Madagascar and Zanzibar, as well as examinations of six-gilled sawsharks in several museum collections provided evidence for a complex of species within Pliotrema warreni Regan. The present manuscript contains a redescription of P. warreni involving the syntypes and additional material, as well as formal descriptions of two new species of Pliotrema Regan. All specimens of both new species were found in the western Indian Ocean. Individuals of the first new species, hereafter referred to as P. kajae sp. nov., were identified originating from Madagascar and the Mascarene Ridge. Specimens of the second new species, hereafter referred to as P. annae sp. nov., were only found off Zanzibar. Pliotrema kajae sp. nov. appears to inhabit upper insular slopes and submarine ridges at depths of 214–320 m, P. annae sp. nov. so far is only known from shallow waters (20–35 m). Both new species differ from P. warreni in a number of characteristics including the known distribution range and fresh coloration. Taxonomical differences include barbels that are situated approximately half way from rostral tip to mouth, with prebarbel length equidistant from barbel origin to symphysis of the upper jaw in P. kajae sp. nov. and P. annae sp. nov. (vs. about two thirds way from rostral tip to mouth, with prebarbel length about twice the distance from barbel origin to symphysis of upper jaw in P. warreni) and rostra that are clearly and slightly constricted between barbel origin and nostrils, respectively (vs. rostrum not constricted). Pliotrema kajae sp. nov. differs from P. annae sp. nov. in a longer snout, more numerous large lateral rostral teeth and upper jaw tooth rows, jaw teeth with (vs. without) sharp basal folds, and coloration, particularly pale to light brown (vs. medium to dark brown) dorsal coloration with (vs. without) two indistinct yellowish stripes. A revised diagnosis of Pliotrema and a key to the species are provided. [ABSTRACT FROM AUTHOR]

Passive acoustic monitoring (PAM) is a powerful method to study the occurrence, movement and behavior of echolocating odontocetes (toothed whales) in the wild. However, in areas occupied by more than one species, echolocation clicks need to be classified into species. The present study investigated whether the echolocation clicks produced by small, at-risk, resident sympatric populations of Indian Ocean humpback dolphin (Sousa plumbea) and Indo-Pacific bottlenose dolphin (Tursiops aduncus) in Menai Bay, Zanzibar, East Africa, could be classified to allow species specific monitoring. Underwater sounds of S. plumbea and T. aduncus groups were recorded using a SoundTrap 202HF in January and June-August 2015. Eight acoustic parameters, i.e. -10 dB duration, peak, centroid, lower -3 and lower -10 dB frequencies, and -3 dB, -10 dB and root-mean-squared bandwidth, were used to describe and compare the two species' echolocation clicks. Statistical analyses showed that S. plumbea clicks had significantly higher peak, centroid, lower -3 and lower -10 dB frequencies compared to T. aduncus, whereas duration and bandwidth parameters were similar for the two species. Random Forest (RF) classifiers were applied to determine parameters that could be used to classify the two species from echolocation clicks and achieved 28.6% and 90.2% correct species classification rates for S. plumbea and T. aduncus, respectively. Both species were classified at a higher rate than expected at random, however the identified classifiers would only be useful for T. aduncus monitoring. The frequency and bandwidth parameters provided most power for species classification. Further study is necessary to identify useful classifiers for S. plumbea. This study represents a first step in acoustic description and classification of S. plumbea and T. aduncus in the western Indian Ocean region, with potential application for future acoustic monitoring of species-specific temporal and spatial occurrence in these sympatric species. [ABSTRACT FROM AUTHOR]

Voltage-gated calcium 3.1 (CaV3.1) channels are absent in healthy mouse β cells and mediate minor T-type Ca2+ currents in healthy rat and human β cells but become evident under diabetic conditions. Whether more active CaV3.1 channels affect insulin secretion and glucose homeostasis remains enigmatic. We addressed this question by enhancing de novo expression of β cell CaV3.1 channels and exploring the consequent impacts on dynamic insulin secretion and glucose homeostasis as well as underlying molecular mechanisms with a series of in vitro and in vivo approaches. We now demonstrate that a recombinant adenovirus encoding enhanced green fluorescent protein-CaV3.1 subunit (Ad-EGFPCaV3.1) efficiently transduced rat and human islets as well as dispersed islet cells. The resulting CaV3.1 channels conducted typical T-type Ca2+ currents, leading to an enhanced basal cytosolic-free Ca2+ concentration ([Ca2+]i). Ad-EGFP-CaV3.1-transduced islets released significantly less insulin under both the basal and first phases following glucose stimulation and could no longer normalize hyperglycemia in recipient rats rendered diabetic by streptozotocin treatment. Furthermore, Ad-EGFP-CaV3.1 transduction reduced phosphorylated FoxO1 in the cytoplasm of INS-1E cells, elevated FoxO1 nuclear retention, and decreased syntaxin 1A, SNAP-25, and synaptotagmin III. These effects were prevented by inhibiting CaV3.1 channels or the Ca2+-dependent phosphatase calcineurin. Enhanced expression of β cell CaV3.1 channels therefore impairs insulin release and glucose homeostasis by means of initial excessive Ca2+ influx, subsequent activation of calcineurin, consequent dephosphorylation and nuclear retention of FoxO1, and eventual FoxO1-mediated down-regulation of β cell exocytotic proteins. The present work thus suggests an elevated expression of CaV3.1 channels plays a significant role in diabetes pathogenesis. [ABSTRACT FROM AUTHOR]

Patients with amyotrophic lateral sclerosis (ALS) often show hallmarks of type 2 diabetes mellitus (T2DM). However, the causal link between ALS and T2DM has remained a mystery. We now demonstrate that 60% of ALS patients with T2DM (ALS-T2DM) have sera that exaggerated K+-induced increases in cytosolic free Ca2+ concentration ([Ca2+]i) in mouse islet cells. The effect was attributed to the presence of pathogenic immunoglobulin Gs (IgGs) in ALST2DM sera. The pathogenic IgGs immunocaptured the voltagedependent Ca2+ (CaV) channel subunit CaVα2δ1 in the plasmamembrane enhancing CaV1 channel-mediated Ca2+ influx and [Ca2+]i, resulting in impaired mitochondrial function. Consequently, impairments in [Ca2+]i dynamics, insulin secretion, and cell viability occurred. These data reveal that patients with ALS-T2DM carry cytotoxic ALS-T2DM-IgG autoantibodies that serve as a causal link between ALS and T2DM by immunoattacking CaαV2δ1 subunits. Our findings may lay the foundation for a pharmacological treatment strategy for patients suffering froma combination of these diseases. [ABSTRACT FROM AUTHOR]

β-Cells respond to peripheral insulin resistance by first increasing circulating insulin during diabetes. Islet remodeling supports this compensation, but its drivers remain poorly understood. Infiltrating macrophages have been implicated in late-stage type 2 diabetes, but relatively little is known on islet resident macrophages, especially during compensatory hyperinsulinemia. We hypothesized that islet resident macrophages would contribute to islet vascular remodeling and hyperinsulinemia during diabetes, the failure of which results in a rapid progression to frank diabetes. We used chemical (clodronate), genetics (CD169-diphtheria toxin receptor mice), or antibody-mediated (colony-stimulating factor 1 receptor α) macrophage ablation methods in diabetic (db/db) and diet-induced models of compensatory hyperinsulinemia to investigate the role of macrophages in islet remodeling. We transplanted islets devoid of macrophages into naïve diabetic mice and assessed the impact on islet vascularization. With the use of the above methods, we showed that macrophage depletion significantly and consistently compromised islet remodeling in terms of size, vascular density, and insulin secretion capacity. Depletion of islet macrophages reduced VEGF-A secretion in both human and mouse islets ex vivo, and this functionally translated to delayed revascularization upon transplantation in vivo. We revealed that islet resident macrophages were associated with islet remodeling and increased insulin secretion during diabetes. This suggests utility in harnessing islet macrophages during this phase to promote islet vascularization, remodeling, and insulin secretion. [ABSTRACT FROM AUTHOR]

Knowledge of population structure, connectivity, and effective population size remains limited for many marine apex predators, including the bull shark Carcharhinus leucas. This large‐bodied coastal shark is distributed worldwide in warm temperate and tropical waters, and uses estuaries and rivers as nurseries. As an apex predator, the bull shark likely plays a vital ecological role within marine food webs, but is at risk due to inshore habitat degradation and various fishing pressures. We investigated the bull shark's global population structure and demographic history by analyzing the genetic diversity of 370 individuals from 11 different locations using 25 microsatellite loci and three mitochondrial genes (CR, nd4, and cytb). Both types of markers revealed clustering between sharks from the Western Atlantic and those from the Western Pacific and the Western Indian Ocean, with no contemporary gene flow. Microsatellite data suggested low differentiation between the Western Indian Ocean and the Western Pacific, but substantial differentiation was found using mitochondrial DNA. Integrating information from both types of markers and using Bayesian computation with a random forest procedure (ABC‐RF), this discordance was found to be due to a complete lack of contemporary gene flow. High genetic connectivity was found both within the Western Indian Ocean and within the Western Pacific. In conclusion, these results suggest important structuring of bull shark populations globally with important gene flow occurring along coastlines, highlighting the need for management and conservation plans on regional scales rather than oceanic basin scale. [ABSTRACT FROM AUTHOR]

Population genetics has been increasingly applied to study large sharks over the last decade. Whilst large shark species are often difficult to study with direct methods, improved knowledge is needed for both population management and conservation, especially for species vulnerable to anthropogenic and climatic impacts. The tiger shark, Galeocerdo cuvier, is an apex predator known to play important direct and indirect roles in tropical and subtropical marine ecosystems. While the global and Indo‐West Pacific population genetic structure of this species has recently been investigated, questions remain over population structure and demographic history within the western Indian (WIO) and within the western Pacific Oceans (WPO). To address the knowledge gap in tiger shark regional population structures, the genetic diversity of 286 individuals sampled in seven localities was investigated using 27 microsatellite loci and three mitochondrial genes (CR,COI, and cytb). A weak genetic differentiation was observed between the WIO and the WPO, suggesting high genetic connectivity. This result agrees with previous studies and highlights the importance of the pelagic behavior of this species to ensure gene flow. Using approximate Bayesian computation to couple information from both nuclear and mitochondrial markers, evidence of a recent bottleneck in the Holocene (2,000–3,000 years ago) was found, which is the most probable cause for the low genetic diversity observed. A contemporary effective population size as low as 111 [43,369] was estimated during the bottleneck. Together, these results indicate low genetic diversity that may reflect a vulnerable population sensitive to regional pressures. Conservation measures are thus needed to protect a species that is classified as Near Threatened. [ABSTRACT FROM AUTHOR]

Pancreatic islets can adapt to oscillatory glucose to produce synchronous insulin pulses. Can islets adapt to other oscillatory stimuli, specifically insulin? To answer this question, we stimulated islets with pulses of exogenous insulin and measured their Ca2+ oscillations. We observed that sufficiently high insulin (> 500 nM) with an optimal pulse period (~ 4 min) could make islets to produce synchronous Ca2+ oscillations. Glucose and insulin, which are key stimulatory factors of islets, modulate islet Ca2+ oscillations differently. Glucose increases the active-to-silent ratio of phases, whereas insulin increases the period of the oscillation. To examine the dual modulation, we adopted a phase oscillator model that incorporated the phase and frequency modulations. This mathematical model showed that out-of-phase oscillations of glucose and insulin were more effective at synchronizing islet Ca2+ oscillations than in-phase stimuli. This finding suggests that a phase shift in glucose and insulin oscillations can enhance inter-islet synchronization. [ABSTRACT FROM AUTHOR]

Thanks to the development of new 3D Imaging techniques, volumetric data of thick samples, especially tissues, are commonly available. Several algorithms were proposed to analyze cells or nuclei in tissues, however these tools are limited to two dimensions. Within any given tissue, cells are not likely to be organized randomly and as such have specific patterns of cell-cell interaction forming complex communication networks. In this paper, we propose a new set of tools as an approach to segment and analyze tissues in 3D with single cell resolution. This new tool box can identify and compute the geographical location of single cells and analyze the potential physical interactions between different cell types and in 3D. As a proof-of-principle, we applied our methodology to investigation of the cyto-architecture of the islets of Langerhans in mice and monkeys. The results obtained here are a significant improvement in current methodologies and provides new insight into the organization of alpha cells and their cellular interactions within the islet's cellular framework. [ABSTRACT FROM AUTHOR]

Insulin is secreted in a pulsatile manner from multiple micro-organs called the islets of Langerhans. The amplitude and phase (shape) of insulin secretion are modulated by numerous factors including glucose. The role of phase modulation in glucose homeostasis is not well understood compared to the obvious contribution of amplitude modulation. In the present study, we measured Ca2+ oscillations in islets as a proxy for insulin pulses, and we observed their frequency and shape changes under constant/alternating glucose stimuli. Here we asked how the phase modulation of insulin pulses contributes to glucose regulation. To directly answer this question, we developed a phenomenological oscillator model that drastically simplifies insulin secretion, but precisely incorporates the observed phase modulation of insulin pulses in response to glucose stimuli. Then, we mathematically modeled how insulin pulses regulate the glucose concentration in the body. The model of insulin oscillation and glucose regulation describes the glucose-insulin feedback loop. The data-based model demonstrates that the existence of phase modulation narrows the range within which the glucose concentration is maintained through the suppression/enhancement of insulin secretion in conjunction with the amplitude modulation of this secretion. The phase modulation is the response of islets to glucose perturbations. When multiple islets are exposed to the same glucose stimuli, they can be entrained to generate synchronous insulin pulses. Thus, we conclude that the phase modulation of insulin pulses is essential for glucose regulation and inter-islet synchronization. [ABSTRACT FROM AUTHOR]

The population structure of the highly mobile marine mammal, the harbor porpoise (Phocoena phocoena), in the Atlantic shelf waters follows a pattern of significant isolation-by-distance. The population structure of harbor porpoises from the Baltic Sea, which is connected with the North Sea through a series of basins separated by shallow underwater ridges, however, is more complex. Here, we investigated the population differentiation of harbor porpoises in European Seas with a special focus on the Baltic Sea and adjacent waters, using a population genomics approach. We used 2872 single nucleotide polymorphisms (SNPs), derived from double digest restriction-site associated DNA sequencing (ddRAD-seq), as well as 13 microsatellite loci and mitochondrial haplotypes for the same set of individuals. Spatial principal components analysis (sPCA), and Bayesian clustering on a subset of SNPs suggest three main groupings at the level of all studied regions: the Black Sea, the North Atlantic, and the Baltic Sea. Furthermore, we observed a distinct separation of the North Sea harbor porpoises from the Baltic Sea populations, and identified splits between porpoise populations within the Baltic Sea. We observed a notable distinction between the Belt Sea and the Inner Baltic Sea sub-regions. Improved delineation of harbor porpoise population assignments for the Baltic based on genomic evidence is important for conservation management of this endangered cetacean in threatened habitats, particularly in the Baltic Sea proper. In addition, we show that SNPs outperform microsatellite markers and demonstrate the utility of RAD-tags from a relatively small, opportunistically sampled cetacean sample set for population diversity and divergence analysis. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic islet transplantation (PIT) to the anterior chamber of the eye (ACE) has been shown to correct hyperglycemia and restore/improve glycemic control in rodents and non‐human primates. These studies also suggested that the eye may be in several ways a superior host site compared to the conventional hepatic portal system. In order to bring this technology to the clinic, it is essential to establish a large‐eyed non‐primate transplantation model. This proposal aims at establishing a rabbit ACE model of allogeneic PIT. We expect to gain insight into isolated islets function as well as ACE grafting efficiency and histological morphology in the large‐eyed rabbit model. Methods: Pancreatic islets (PI) were isolated from Dutch Belted rabbits by injection of collagenase A into the pancreatic interstitium, digestion and hand picking under a stereo microscope. PI were cultured in RPMI medium overnight in a standard tissue culture incubator prior to assessment of purity. In vitro functional capacity of rabbit PI was assessed by glucose‐stimulated insulin release and intracellular Ca2+ imaging assays. PI were injected into the ACE an allogenic Dutch Belted rabbit using surgical procedures routinely applied in ophthalmology. PI engraftment and cellular content was analysed by anterior segment optical coherence tomography (ASOCT) and immunohistofluorescence (IHF). Results: Isolated PI were of high purity with an approximate yield of 600–800 islets per pancreas. Preliminary results of functional capacity demonstrate that islets are responsive to high glucose stimulus, despite some variability. Allogeneic transplantation of isolated PI into the ACE of a Dutch Belted rabbit was followed by ASOCT. Engraftment was confirmed by IHF for vimentin. IHF suggests ACE engrafted islets are viable and maintain alpha, beta and delta cells. Conclusions: The presented isolation method renders high purity and functional rabbit PI. Allogeneic transplantation of PI into the ACE was successful using clinically relevant procedures and resulted in islets engraftment and long‐term survival. These results may have implications for the clinical treatment of diabetes mellitus, particularly regarding patients with indications for PIT. [ABSTRACT FROM AUTHOR]

Ex vivo expansion of endocrine cells constitutes an interesting alternative to be able to match the unmet need of transplantable pancreatic islets. However, endocrine cells become fragile once removed from their extracellular matrix (ECM) and typically become senescent and loose insulin expression during conventional 2D culture. Herein we develop a protocol where 3D silk matrices functionalized with ECM-derived motifs are used for generation of insulin-secreting islet-like clusters from mouse and human primary cells. The obtained clusters were shown to attain an islet-like spheroid shape and to maintain functional insulin release upon glucose stimulation in vitro . Furthermore, in vivo imaging of transplanted murine clusters showed engraftment with increasing vessel formation during time. There was no sign of cell death and the clusters maintained or increased in size throughout the period, thus suggesting a suitable cluster size for transplantation. [ABSTRACT FROM AUTHOR]

Understanding temporal patterns in distribution, occurrence and behaviour is vital for the effective conservation of cetaceans. This study used cetacean click detectors (C-PODs) to investigate spatial and temporal variation in occurrence and foraging activity of the Indo-Pacific bottlenose (Tursiops aduncus) and Indian Ocean humpback (Sousa plumbea) dolphins resident in the Menai Bay Conservation Area (MBCA), Zanzibar, Tanzania. Occurrence was measured using detection positive minutes. Inter-click intervals were used to identify terminal buzz vocalisations, allowing for analysis of foraging activity. Data were analysed in relation to spatial (location) and temporal (monsoon season, diel phase and tidal phase) variables. Results showed significantly increased occurrence and foraging activity of dolphins in southern areas and during hours of darkness. Higher occurrence at night was not explained by diel variation in echolocation rate and so were considered representative of occurrence patterns. Both tidal phase and monsoon season influenced occurrence but results varied among sites, with no general patterns found. Foraging activity was greatest during hours of darkness, High water and Flood tidal phases. Comparisons of echolocation data among sites suggested differences in the broadband click spectra of MBCA dolphins, possibly indicative of species differences. These dolphin populations are threatened by unsustainable fisheries bycatch and tourism activities. The spatial and temporal patterns identified in this study have implications for future conservation and management actions with regards to these two threats. Further, the results indicate future potential for using passive acoustics to identify and monitor the occurrence of these two species in areas where they co-exist. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) imaging and sound experimental measurements were used to reconstruct the acoustic properties (density, velocity, and impedance) of the forehead tissues of a deceased pygmy sperm whale (Kogia breviceps). The forehead was segmented along the body axis and sectioned into cross section slices, which were further cut into sample pieces for measurements. Hounsfield units (HUs) of the corresponding measured pieces were obtained from CT scans, and regression analyses were conducted to investigate the linear relationships between the tissues' HUs and velocity, and HUs and density. The distributions of the acoustic properties of the head at axial, coronal, and sagittal cross sections were reconstructed, revealing that the nasal passage system was asymmetric and the cornucopia-shaped spermaceti organ was in the right nasal passage, surrounded by tissues and airsacs. A distinct dense theca was discovered in the posterior-dorsal area of the melon, which was characterized by low velocity in the inner core and high velocity in the outer region. Statistical analyses revealed significant differences in density, velocity, and acoustic impedance between all four structures, melon, spermaceti organ, muscle, and connective tissue (p<0.001). The obtained acoustic properties of the forehead tissues provide important information for understanding the species' bioacoustic characteristics. [ABSTRACT FROM AUTHOR]

Nature’s fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5’s active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases. [ABSTRACT FROM AUTHOR]

Inflammation and impaired mitochondrial oxidative phosphorylation are considered key players in the development of several metabolic disorders, including diabetes. We have previously shown inflammation and mitochondrial dysfunction in the hypothalamus of an animal model for anorexia, the anx/anx mouse. Moreover, increased incidence of eating disorders, e.g., anorexia nervosa, has been observed in diabetic individuals. In the present investigation we evaluated whether impaired mitochondrial phosphorylation and inflammation also occur in endocrine pancreas of anorectic mice, and if glucose homeostasis is disturbed. We show that anx/anx mice exhibit marked glucose intolerance associated with reduced insulin release following an intraperitoneal injection of glucose. In contrast, insulin release from isolated anx/anx islets is increased after stimulation with glucose or KCl. In isolated anx/anx islets there is a strong downregulation of the mitochondrial complex I (CI) assembly factor, NADH dehydrogenase (ubiquinone) 1 subcomplex, assembly factor 1 (Ndufaf1), and a reduced CI activity. In addition, we show elevated concentrations of free fatty acids (FFAs) in anx/anx serum and increased macrophage infiltration (indicative of inflammation) in anx/anx islets. However, isolated islets from anx/anx mice cultured in the absence of FFAs do not exhibit increased inflammation. We conclude that the phenotype of the endocrine pancreas of the anx/anx mouse is characterized by increased levels of circulating FFAs, as well as inflammation, which can inhibit insulin secretion in vivo. The anx/anx mouse may represent a useful tool for studying molecular mechanisms underlying the association between diabetes and eating disorders. [ABSTRACT FROM AUTHOR]