Release Sites Research Articles

Assessing invasion risks using EICAT-based expert elicitation: application to a conservation translocation

Conservation translocations are widely used to recover threatened species, but can pose risks to recipient ecosystems, particularly in the case of conservation introductions. Because of limited data and uncertainty, risk assessments for such projects often rely on extrapolated evidence and expert opinion, further complicating decision making. The Environmental Impact Classification for Alien Taxa (EICAT) serves to classify the realised impacts of invasive species. We developed a protocol combining EICAT and formal expert elicitation to predict these impacts. We applied our protocol to the extinct-in-the-wild sihek (Guam kingfisher; Todiramphus cinnamominus), for which introduction outside the known historical range is being considered. We elicited from multiple experts probability estimates of impact levels across four impact mechanisms and five candidate release sites. We aggregated estimates using simulation-based and Bayesian approaches, with and without accounting for expert confidence. Experts generally agreed that sihek introduction might impact the recipient ecosystem through predation, competition, and disease, although they disagreed about the likely impact levels. Releases to Palmyra Atoll were considered to pose the lowest risk across candidate sites, so this site was selected for further detailed ecological assessments and risk mitigation efforts. EICAT, with its standardized impact mechanisms and definitions, helped reduce the linguistic uncertainty and subjectivity common to expert-based assessments. Expressing judgments as probabilities allowed us to evaluate uncertainty transparently and to assess the weight of expert confidence on the overall risk estimation. Formal quantitative elicitation and aggregation then allowed a transparent evaluation of results, facilitating communication with stakeholders and decision-makers.

Differential SNARE chaperoning by Munc13-1 and Munc18-1 dictates fusion pore fate at the release site.

The regulated release of chemical messengers is crucial for cell-to-cell communication; abnormalities in which impact coordinated human body function. During vesicular secretion, multiple SNARE complexes assemble at the release site, leading to fusion pore opening. How membrane fusion regulators act on heterogeneous SNARE populations to assemble fusion pores in a timely and synchronized manner, is unknown. Here, we demonstrate the role of SNARE chaperones Munc13-1 and Munc18-1 in rescuing individual nascent fusion pores from their diacylglycerol lipid-mediated inhibitory states. At the onset of membrane fusion, Munc13-1 clusters multiple SNARE complexes at the release site and synchronizes release events, while Munc18-1 stoichiometrically interacts with trans-SNARE complexes to enhance N- to C-terminal zippering. When both Munc proteins are present simultaneously, they differentially access dynamic trans-SNARE complexes to regulate pore properties. Overall, Munc proteins' direct action on fusion pore assembly indicates their role in controlling quantal size during vesicular secretion.

Evaluation of trial reintroductions of two extinct in the wild reptile species on Christmas Island

AbstractConservation reintroductions play a vital role in the recovery of threatened species, and clear goals and objectives are essential for evaluating their effectiveness. In this study, we assessed short‐term success (<18 months) of trial reintroductions of the Extinct in the Wild blue‐tailed skink (Cryptoblepharus egeriae) and Lister's gecko (Lepidodactylus listeri) on Christmas Island. Our evaluation criteria focused on body condition, reproduction, habitat suitability, survival and population growth. In 2018 and 2019, 170 C. egeriae and 160 L. listeri were translocated from a local captive breeding facility to a 2600 m2 outdoor fenced enclosure designed to exclude a predatory snake. Despite body condition declining immediately following release for both species, it had improved by 6 months post‐release. We also detected successful reproduction in both species. Apparent survival was high for C. egeriae but low for L. listeri, and population growth was only evident in C. egeriae. We were unable to determine whether low survival of L. listeri in the release site was due to high post‐release dispersal (beyond the exclosure) or mortality. Both species selected habitats that contained high rock and log cover and avoided areas with low ground cover. Appropriate assessment criteria, as utilized in this study, enable objective and timely evaluations of reintroduction success, thereby facilitating the improvement and refinement of reintroduction protocols. Our study showed that C. egeriae can establish (in the short‐ to medium‐term) in a site from which a principal threat has been excluded and undergo rapid population growth, whereas under current conditions L. listeri cannot. However, we also demonstrate that such medium‐term success may not lead to long‐term success, as the rapid increase in C. egeriae population was reversed between 29 and 31 months after release because the barrier used to exclude an invasive predator, the wolf snake (Lycodon capucinus), was breached.

Anomalous diffusion of synaptic vesicles and its influences on spontaneous and evoked neurotransmission.

Neurons in the central nervous system communicate with each other by activating billions of tiny synaptic boutons distributed along their fine axons. These presynaptic varicosities are very crowded environments, comprising hundreds of synaptic vesicles. Only a fraction of these vesicles can be recruited in a single release episode, either spontaneous or evoked by action potentials. Since the seminal work by Fatt and Katz, spontaneous release has been modelled as a memoryless process. Nevertheless, at central synapses, experimental evidence indicates more complex features, including non-exponential distributions of release intervals and power-law behaviour in their rate. To describe these features, we developed a probabilistic model of spontaneous release based on Brownian motion of synaptic vesicles in the presynaptic environment. To account for different diffusion regimes, we based our simulations on fractional Brownian motion. We show that this model can predict both deviation from the Poisson hypothesis and power-law features in experimental quantal release series, thus suggesting that the vesicular motion by diffusion could per se explain the emergence of these properties. We demonstrate the efficacy of our modelling approach using electrophysiological recordings at single synaptic boutons and ultrastructural data. When this approach was used to simulate evoked responses, we found that the replenishment of the readily releasable pool driven by Brownian motion of vesicles can reproduce the characteristic binomial release distributions seen experimentally. We believe that our modelling approach supports the idea that vesicle diffusion and readily releasable pool dynamics are crucial factors for the physiological functioning of neuronal communication. KEY POINTS: We developed a new probabilistic model of spontaneous and evoked vesicle fusion based on simple biophysical assumptions, including the motion of vesicles before they dock to the release site. We provide closed-form equations for the interval distribution of spontaneous releases in the special case of Brownian diffusion of vesicles, showing that a power-law heavy tail is generated. Fractional Brownian motion (fBm) was exploited to simulate anomalous vesicle diffusion, including directed and non-directed motion, by varying the Hurst exponent. We show that our model predicts non-linear features observed in experimental spontaneous quantal release series as well as ultrastructural data of synaptic vesicles spatial distribution. Evoked exocytosis based on a diffusion-replenished readily releasable pool might explain the emergence of power-law behaviour in neuronal activity.

Rewilding landscapes with apex predators: cheetah (Acinonyx jubatus) movements reveal the importance of environmental and individual contexts

Rewilding landscapes through species or population restoration is an increasingly applied practice in biological conservation. There is expanding interest in wildlife release projects for apex predator population augmentation or reintroductions in historical ranges. Cheetahs (Acinonyx jubatus) are an IUCN Vulnerable-listed species with a declining global population facing major threats, which in southern Africa primarily include lethal persecution on livestock farms and bush encroachment transforming open habitats to woody areas. We used GPS radiocollars to monitor ten adult cheetahs from 2007 – 2018 in the Central Plateau of Namibia encompassing an area restored as an open savanna field (13.7 km2) located in a matrix of woodland savanna affected by bush encroachment. We generated a set of a priori hypotheses that tested the effects of various factors on cheetah movements indexed by step length. We compared cheetah movement metrics based on their history as wild, rehabilitated, and/or translocated individuals. Day/night activity, habitat type, and habitat edges were significant predictors of cheetah movement. Wild resident cheetahs displayed significantly longer steps than the other cheetah classes, possibly suggesting increased territorial behaviour in response to the presence of introduced cheetahs. Some cheetahs temporally segregated by moving extensively during daytime, but most individuals were primarily active during crepuscular periods. Small prey remained constant across time, whereas large prey declined over the study period. Cheetahs appeared to adjust behaviourally by increasing movements in years when large prey were scarce. Cheetahs appeared to be ecologically adaptable and behaviourally flexible in response to varying prey populations and when translocated to new environments, specifically at the interface between bush-encroached woodland and open savanna. Environmental settings and animal history need to be carefully considered in rewilding and ecosystem restoration, and monitoring of released and resident individuals, if present, is important to understand ecological dynamics at release sites.

Climate modelling of the potential distribution in South Africa of two Zygogramma species (Coleoptera: Chrysomelidae) released for the biological control of invasive weed Tithoniarotundifolia (Asteraceae: Heliantheae)

Two Mexican leaf-feeding beetles, Zygogramma piceicollis (Stål) and Zygogramma signatipennis (Stål) (Coleoptera: Chrysomelidae), were released in South Africa for the biological control of the invasive species Tithonia rotundifolia (Mill.) S.E. Blake (Asteraceae: Heliantheae). The aim of this study was to predict the potential of these beetles to establish and spread in South Africa, using MaxEnt climate modelling that incorporated locality data recorded in Mexico between 2008 and 2019 and data from the Global Biodiversity Information Facility. Zygogramma signatipennis displayed a wider distribution than Z. piceicollis in Mexico, with some overlap between the two species. The average receiver operating characteristic curves obtained for Z. piceicollis and Z. signatipennis predicted high mean area under curve values of 0.910 and 0.885, respectively. Jackknife tests revealed that mean annual temperature had the highest gain when used in isolation for Z. piceicollis, compared with minimum precipitation of the driest month for Z. signatipennis. These tests also revealed that the highest and lowest contributing environmental variables for Z. piceicollis and Z. signatipennis were minimum precipitation of the driest month (37.9 and 46.7%) and maximum annual temperature of the warmest month (3.8 and 12.3%), respectively. MaxEnt modelling predicted that at least six of South Africa’s nine provinces provide regions that would support the proliferation of both beetles, with conditions best suited for Z. piceicollis. Despite predictions that both beetles should establish throughout the range of T. rotundifolia in South Africa, their realized establishment has so far been poor. Other factors, besides climate, including release size, site destructions, drought, soil moisture and texture could be constraining establishment.

The effects of intensive trapping on invasive round goby densities.

The round goby (Neogobius melanostomus) is an invasive benthic fish first introduced to the Laurentian Great Lakes in 1990 that has negatively impacted native fishes through increased competition for food and habitat, aggressive interactions, and egg predation. While complete eradication of the round goby is currently not possible, intensive trapping in designated areas during spawning seasons could potentially protect critical native fish spawning habitats. Baited minnow traps were spaced 10 meters apart in shallow water along a 100-meter stretch of shoreline within the Duluth-Superior Harbor during the round goby breeding period (June to October) with captured round gobies removed from interior traps (N = 10) every 48 hours. These traps were bracketed by two pairs of reference traps deployed weekly for 48 hours, from which round gobies were also tagged and released. The number of round gobies captured in the interior traps declined by 67% compared to reference traps over the course of the study, with extended periods of no captures. The tagged round gobies showed high site affinity, with 82.8% of tagged fish recaptured at the previous release site. The results indicate that even at open water sites, which allow natural migration of round gobies into the area, extensive trapping could reduce local population numbers.

Harnessing <i>Wolbachia</i> to Reduce Dengue Transmission - a Review

In this article, we discuss the possible, underlying molecular and biological basis of dengue case reduction by Wolbachia-infected mosquitoes, their field releases trial, and mathematical modelling of reduction in transmission of DENV attributable to the presence of Wolbachia. This study suggests that Wolbachia-infected DENV control could reduce dengue incidences up to 40.3 to 96% in the field release sites and A laboratory-based trial reported 100% suppression when Wolbachia-infected male mosquitoes were released. Moreover, Mathematical modeling predicted promising results in dengue reduction by Wolbachia. Documented evidence in this study support Wolbachia as a novel vector control approach to limit dengue transmission.

Different states of synaptic vesicle priming explain target cell type–dependent differences in neurotransmitter release

Pronounced differences in neurotransmitter release from a given presynaptic neuron, depending on the synaptic target, are among the most intriguing features of cortical networks. Hippocampal pyramidal cells (PCs) release glutamate with low probability to somatostatin expressing oriens-lacunosum-moleculare (O-LM) interneurons (INs), and the postsynaptic responses show robust short-term facilitation, whereas the release from the same presynaptic axons onto fast-spiking INs (FSINs) is ~10-fold higher and the excitatory postsynaptic currents (EPSCs) display depression. The mechanisms underlying these vastly different synaptic behaviors have not been conclusively identified. Here, we applied a combined functional, pharmacological, and modeling approach to address whether the main difference lies in the action potential-evoked fusion or else in upstream priming processes of synaptic vesicles (SVs). A sequential two-step SV priming model was fitted to the peak amplitudes of unitary EPSCs recorded in response to complex trains of presynaptic stimuli in acute hippocampal slices of adult mice. At PC-FSIN connections, the fusion probability (Pfusion) of well-primed SVs is 0.6, and 44% of docked SVs are in a fusion-competent state. At PC-O-LM synapses, Pfusion is only 40% lower (0.36), whereas the fraction of well-primed SVs is 6.5-fold smaller. Pharmacological enhancement of fusion by 4-AP and priming by PDBU was recaptured by the model with a selective increase of Pfusion and the fraction of well-primed SVs, respectively. Our results demonstrate that the low fidelity of transmission at PC-O-LM synapses can be explained by a low occupancy of the release sites by well-primed SVs.

Inhibiting the cGAS-STING Pathway in Ulcerative Colitis with Programmable Micelles.

Ulcerative colitis is a chronic condition in which a dysregulated immune response contributes to the acute intestinal inflammation of the colon. Current clinical therapies often exhibit limited efficacy and undesirable side effects. Here, programmable nanomicelles were designed for colitis treatment and loaded with RU.521, an inhibitor of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. STING-inhibiting micelles (SIMs) comprise hyaluronic acid-stearic acid conjugates and include a reactive oxygen species (ROS)-responsive thioketal linker. SIMs were designed to selectively accumulate at the site of inflammation and trigger drug release in the presence of ROS. Our in vitro studies in macrophages and in vivo studies in a murine model of colitis demonstrated that SIMs leverage HA-CD44 binding to target sites of inflammation. Oral delivery of SIMs to mice in both preventive and delayed therapeutic models ameliorated colitis's severity by reducing STING expression, suppressing the secretion of proinflammatory cytokines, enabling bodyweight recovery, protecting mice from colon shortening, and restoring colonic epithelium. In vivo end points combined with metabolomics identified key metabolites with a therapeutic role in reducing intestinal and mucosal inflammation. Our findings highlight the significance of programmable delivery platforms that downregulate inflammatory pathways at the intestinal mucosa for managing inflammatory bowel diseases.

Single-molecule tracking reveals dual front door/back door inhibition of Cel7A cellulase by its product cellobiose

Degrading cellulose is a key step in the processing of lignocellulosic biomass into bioethanol. Cellobiose, the disaccharide product of cellulose degradation, has been shown to inhibit cellulase activity, but the mechanisms underlying product inhibition are not clear. We combined single-molecule imaging and biochemical investigations with the goal of revealing the mechanism by which cellobiose inhibits the activity of Trichoderma reesei Cel7A, a well-characterized exo-cellulase. We find that cellobiose slows the processive velocity of Cel7A and shortens the distance moved per encounter; effects that can be explained by cellobiose binding to the product release site of the enzyme. Cellobiose also strongly inhibits the binding of Cel7A to immobilized cellulose, with a Ki of 2.1 mM. The isolated catalytic domain (CD) of Cel7A was also inhibited to a similar degree by cellobiose, and binding of an isolated carbohydrate-binding module to cellulose was not inhibited by cellobiose, suggesting that cellobiose acts on the CD alone. Finally, cellopentaose inhibited Cel7A binding at micromolar concentrations without affecting the enzyme's velocity of movement along cellulose. Together, these results suggest that cellobiose inhibits Cel7A activity both by binding to the "back door" product release site to slow activity and to the "front door" substrate-binding tunnel to inhibit interaction with cellulose. These findings point to strategies for engineering cellulases to reduce product inhibition and enhance cellulose degradation, supporting the growth of a sustainable bioeconomy.

Nitroxyl donating and visualization with a coumarin-based fluorescence probe

Nitroxyl (HNO), the single-electron reduction product of nitric oxide (NO), has attracted great interest in the treatment of congestive heart failure in clinical trials. In this paper, we describe the first coumarin-based compound N-hydroxy-2-oxo-2H-chromene-6-sulfonamide (CD1) as a dualfunctional HNO donor, which can release both an HNO signaling molecule and a fluorescent reporter. Under physiological conditions (pH 7.4 and 37 °C), the CD1 HNO donor can readily decompose with a half-life of ∼90 min. The corresponding stoichiometry HNO from the CD1 donor was confirmed using both Vitamin B12 and phosphine compound traps. In addition to HNO releasing, specifically, the degradation product 2-oxo-2H-chromene-6-sulfinate (CS1) was generated as a fluorescent marker during the decomposition. Therefore, the HNO amount released in situ can be accurately monitored through fluorescence generation. As compared to the CD1 donor, the fluorescence intensity increased by about 4.9-fold. The concentration limit of detection of HNO releasing was determined to be ∼0.13 μM according to the fluorescence generation of CS1 at physiological conditions. Moreover, the bioimaging of the CD1 donor was demonstrated in the cell culture of HeLa cells, where the intracellular fluorescence signals were observed, inferring the site of HNO release. Finally, we anticipate that this novel coumarin-based CD1 donor opens a new platform for exploring the biology of HNO.

Gene expression profiles of white bass (Morone chrysops) and hybrid striped bass (M. chrysops x M. saxatilis) gill tissue following Flavobacterium covae infection

Columnaris disease is a prevalent disease in freshwater environments caused by the ubiquitous aquatic pathogen Flavobacterium species. Adhesion to the external mucosal surfaces of fishes is the initial stage of infection, and the gills specifically have been identified as both a primary target and release site for this pathogen. Demonstrated here and in previous research, the hybrid striped bass (Morone chrysops x M. saxatilis), a prominent United States aquaculture product, is more susceptible to infection with F. covae than the maternal white bass (M. chrysops) parental species. To further elucidate the mechanisms underlying differences in resistance between these fish we examined gill gene expression profiles using RNA sequencing at different timepoints after F. covae infection. Patterns of differential gene expression and association with key enrichment terms indicate the effective immune response observed in white bass includes the up-regulation of multiple cytokines (IL-1β, IL-17C, TNF-α, G-CSF, IL-8, CCL16, CXCL9), hepcidins (HAMP and HAMP2), ribosomal subunit components (e.g., RPL13), and, interestingly, the down-regulation of leptin (LEPA) during initial (1 – 4 h) stages of infection. Conversely, up-regulation of the same genes was not detected in hybrid striped bass until 24 h after infection, indicating a delay in immune response mechanisms that is ultimately ineffective in protecting the host, as this was concurrent with the onset of mortality in these fish. Collectively, the presented results include several putative pathways and candidate genes for further investigation toward characterizing immune defense mechanisms underlying the resistance (white bass) and susceptibility (hybrid striped bass) for selective breeding efforts and/or biotechnological intervention.

Aroplectrus dimerus (Hymenoptera: Eulophidae), Ectoparasitoid of the Nettle Caterpillar, Oxyplax pallivitta (Lepidoptera: Limacodidae): Evaluation in the Hawaiian Islands.

The stinging nettle caterpillar, Oxyplax (syn. Darna) pallivitta (Lepidoptera: Limacodidae), is a serious invasive pest of agricultural products and a health hazard on the Hawaiian Islands first discovered in 2001. Nursery workers and homeowners have been stung by the caterpillars while handling their plants, especially rhapis palms (Rhapis sp.). Throughout its invaded range, it causes widespread damage, including the many cultivated and native palm species that have grown in Hawaii. Larvae contain urticating hairs that secrete a toxin, causing painful skin swelling and irritation on contact. Horticulture and nursery products impacted by the limacodid pest are estimated at $84.3 million (2018 value). Suppression efforts with pesticides and lure traps were ineffective, and the moth population continued to spread to major Hawaiian Islands (Hawaii, Kauai, Maui, Oahu). The introduction of specific biological control agents from the native region was thought to be the long-term solution for this invasive pest. Initial exploration in Indonesia and Thailand resulted in the introduction of a pupal ectoparasitoid, Nesolynx sp. (Hymenoptera: Eulophidae: Tetrastichinae), that was not specific. The oriental wasp, Aroplectrus dimerus Lin (Hymenoptera: Eulophidae: Eulophinae), idiobiont gregarious ectoparasitoid of the stinging nettle caterpillar, was introduced from Taiwan in 2004 for host specificity studies and biocontrol in Hawaii. Host range testing showed the parasitoid attacked only limacodid species, and it was approved for field release in 2010. The parasitoid identity, host specificity under containment facility conditions, reproductive performance, and colonization on the major infested sites were assessed. A total of 13,379 parasitoids were colonized on 162 release sites on four Hawaiian Islands. Evaluations were conducted using field surveys of larvae, pupal counts, and male lure traps. Field parasitism was thoroughly investigated on Oahu Island, averaging 18.9 ± 5.6% of 3923 collected larvae during 2010-2023. The numbers of male moths caught/trap/month were significantly reduced on Oahu Island (p < 0.05). Recently, the hyperparasitoid, Pediobius imbreus Walker (Hymenoptera: Eulophidae: Entedoninae), was detected, reducing the efficiency of A. dimerus in the field. The mean hyperparasitism of A. dimerus pupae was 27.3 ± 7.6% on Oahu Island. There was no detailed biological assessment for A. dimerus or its field evaluation available in scientific literature. Results were discussed regarding the potential use of A. dimerus in biocontrol elsewhere if the stinging nettle caterpillar was invaded in the future.

Impulse generated from detonation waves in non-premixed and partially premixed reactants

Rotating detonation engines (RDEs) are the subject of research in the combustion community due to the prospects of enhanced thermal efficiency and power density when compared to current deflagrative-based aerospace combustors. Many current simulations presume premixed reactants and therefore miss the important characteristics of transient mixing, wave-induced mixing, and injector design/spacing that are known to play a pivotal role in the system performance. Very ambitious large eddy simulations are being conducted, but necessarily on a limited number of realistic and complex cases, thus limiting their utility in deriving fundamental understanding. For these reasons, a two dimensional parametric study was conducted to assess propagation of a detonation across an idealized array of mixing/injection sites, parametrically characterized by the width and axial mixing profile.Under such non-premixed conditions, discrete energy release and interdependence are observed. The discrete energy release sites frequently create pressures that exceed idealized Chapman-Jouguet (CJ) predictions based on perfect and uniform mixtures. The local higher pressure is shown to be caused by delayed heat release behind the shock, near constant pressure combustion, and additional compression due to the non-uniformities present. The resulting compression and the near constant pressure combustion are accompanied by time scale separation of exothermic and endothermic reactions due to the mixing efficiencies in the non/poorly-premixed cases. In contrast, the better mixed cases show that the detonation wave is sustained but unburnt fuel and oxidizer exist behind the main combustion wave and impulse performance suffers. Results show that for the conditions modeled there exists an optimal injector spacing to maximize the impulse produced and that discrete injection impulses can exceed that of the premixed systems. These somewhat counter-intuitive results imply that the detailed mixing evolution, provoked by the passage of the wave can lead to an extended heat release zone that elevates the pressure over a longer distance along the wavefront. These revelations provide potential for optimizing injector configurations for real non-premixed systems in order to exploit these physics.

A hydrophobic groove in secretagogin allows for alternate interactions with SNAP-25 and syntaxin-4 in endocrine tissues

Vesicular release of neurotransmitters and hormones relies on the dynamic assembly of the exocytosis/trans-SNARE complex through sequential interactions of synaptobrevins, syntaxins, and SNAP-25. Despite SNARE-mediated release being fundamental for intercellular communication in all excitable tissues, the role of auxiliary proteins modulating the import of reserve vesicles to the active zone, and thus, scaling repetitive exocytosis remains less explored. Secretagogin is a Ca2+-sensor protein with SNAP-25 being its only known interacting partner. SNAP-25 anchors readily releasable vesicles within the active zone, thus being instrumental for 1st phase release. However, genetic deletion of secretagogin impedes 2nd phase release instead, calling for the existence of alternative protein-protein interactions. Here, we screened the secretagogin interactome in the brain and pancreas, and found syntaxin-4 grossly overrepresented. Ca2+-loaded secretagogin interacted with syntaxin-4 at nanomolar affinity and 1:1 stoichiometry. Crystal structures of the protein complexes revealed a hydrophobic groove in secretagogin for the binding of syntaxin-4. This groove was also used to bind SNAP-25. In mixtures of equimolar recombinant proteins, SNAP-25 was sequestered by secretagogin in competition with syntaxin-4. Kd differences suggested that secretagogin could shape unidirectional vesicle movement by sequential interactions, a hypothesis supported by in vitro biological data. This mechanism could facilitate the movement of transport vesicles toward release sites, particularly in the endocrine pancreas where secretagogin, SNAP-25, and syntaxin-4 coexist in both α- and β-cells. Thus, secretagogin could modulate the pace and fidelity of vesicular hormone release by differential protein interactions.

Identifying Important Areas for the Release of Five Endemic Species in a Mountainous Landscape: Inference from Spatial Modeling Techniques

Efforts to release animals resulting from evacuation and rehabilitation into their natural habitats are important practices in wildlife conservation. Before releasing the animals, it is important to assess the habitat suitability of the areas to support the existence of the animals in the long run. Yet, there is limited study of habitat suitability assessment on national parks as release locations for wild animals. This study aimed to assess the suitable habitat of five charismatic animal species, i.e., Panthera pardus melas, Hylobates moloch, Prinonailurus bengalensis, Nycticebus javanicus, and Nisaetus bartelsi, in Gunung Halimun Salak National Park using Maxent, and to determine potential locations for releasing animal’s species. Models for the P. p. melas show 47,619 ha and 21,391 ha, respectively, suitable as habitat and potential release location, for H. moloch, each is 57,537 ha and 33,471 ha, for P. bengalensis, each is 25,460 ha and 17.189 ha, for N. javanicus, each is 29,848 ha and 15,578 ha, and for N. bartelsi, each is 44,426 ha and 25,660 ha. Our study shows that a suitable habitat can be critical in choosing a wildlife release site. Further consideration of conflict mitigation and practicalities is required to achieve the long-term existence of released species.

Can more be done to optimise the effect of mesalazine for IBD patients with mild to moderate ulcerative colitis?

Background Ulcerative colitis (UC) is characterised by chronic mucosal inflammation primarily in the colon. Guidelines recommend mesalazine as first-line therapy for induction of maintenance in mild-to-moderate Ulcerative colitis. Patients' preferences, response to treatment, site and extent of inflammation and cost are important considerations when selecting mesalazine therapy. Aims/Methods This article reviews mesalazine's role in ulcerative colitis and explores the factors to consider when optimising mesalazine-based therapy. Findings Up to two-thirds of patients fail to respond to induction therapy within 8 weeks, thereby prompting a switch of formulations or escalation to oral corticosteroids. While there are no major variations in efficacy, different mesalazine formulations are not interchangeable because of differences in mode of drug delivery, site of drug release and excipients. Switching mesalazine products before escalating therapy may, therefore, spare patients from wider side effects and higher costs. Conclusions Optimising mesalazine-based therapy requires individualised treatment plans based on patient preferences, site and extent of inflammation, response to treatment and potential side effects. An algorithm exists to guide the selection of alternative mesalazine formulations when required.

Can more be done to optimise the effect of mesalazine for IBD patients with mild to moderate ulcerative colitis?

Background Ulcerative colitis (UC) is characterised by chronic mucosal inflammation primarily in the colon. Guidelines recommend mesalazine as first-line therapy for induction of maintenance in mild-to-moderate Ulcerative colitis. Patients' preferences, response to treatment, site and extent of inflammation and cost are important considerations when selecting mesalazine therapy. Aims/Methods This article reviews mesalazine's role in ulcerative colitis and explores the factors to consider when optimising mesalazine-based therapy. Findings Up to two-thirds of patients fail to respond to induction therapy within 8 weeks, thereby prompting a switch of formulations or escalation to oral corticosteroids. While there are no major variations in efficacy, different mesalazine formulations are not interchangeable because of differences in mode of drug delivery, site of drug release and excipients. Switching mesalazine products before escalating therapy may, therefore, spare patients from wider side effects and higher costs. Conclusions Optimising mesalazine-based therapy requires individualised treatment plans based on patient preferences, site and extent of inflammation, response to treatment and potential side effects. An algorithm exists to guide the selection of alternative mesalazine formulations when required.

Gastrointestinal release site for delayed release and gelatin capsules in healthy dogs.

Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60-90) to release BIPS™ compared to gelatin capsules (15 min, range 15-30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.