Human disturbance and the activity patterns and temporal overlap of tapirs and jaguars in reserves of NW Belize

Human disturbance from tourism and other non-consumptive activities in protected areas may be stressful to wildlife. Animals may move away in space or time to avoid human interaction. For species of particular conservation concern, such as Baird's tapirs (Tapirus bairdii) and jaguars (Panthera onca), a better understanding of how they respond to different levels and types of disturbance is needed in order to manage human visitation to parks in ways that minimize negative outcomes for wildlife. We describe the overlap in activity patterns of tapirs, jaguars, and humans at logged and unlogged sites and at places with low versus high human visitation using camera survey data from protected areas of NW Belize, 2013–2016. Tapirs were nocturnal in all study sites, with > 80% of all tapir detections occurring between 1900 hr and 0500 hr. Their activity patterns were not different in unlogged versus logged sites and did not change with increased human traffic. Jaguars were cathemeral across sites but had more nocturnal activity at the site with the most human impact. Activity pattern overlap between tapirs and jaguars did not differ significantly between logged and unlogged sites, nor between areas with low and high human activity. Human traffic increased from 2013 to 2016 at most of the study locations. In conclusion, this camera trap dataset suggests that non-consumptive human disturbance does not alter the activity patterns of tapirs and jaguars in protected areas lacking hunting pressure.     

New structure–activity relationship studies in a series of N,N-bis(cyclohexanol)amine aryl esters as potent reversers of P-glycoprotein-mediated multidrug resistance (MDR)

As a continuation of previous research on a new series of potent and efficacious P-gp-dependent multidrug resistant (MDR) reversers with a N,N-bis(cyclohexanol)amine scaffold, we have designed and synthesized several analogs by modulation of the two aromatic moieties linked through ester functions to the N,N-bis(cyclohexanol)amine, aiming to optimize activity and to extend structure–activity relationships (SAR) within the series. This scaffold, when esterified with two different aromatic carboxylic acids, gives origin to four geometric isomers (cis/trans, trans/trans, cis/cis and trans/cis).The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Most of them resulted in being potent modulators of the extrusion pump P-gp, showing potency values ([I]_0.5) in the submicromolar and nanomolar range. Of these, compounds 2b, 2c, 3d, 5a–d and 6d, showed excellent efficacy with a α_max close to 1. Selected compounds (2d, 3a, 3b, 5a–d) were further studied to evaluate their doxorubicin cytotoxicity potentiation (RF) on doxorubicin-resistant erythroleukemia K562 cells and were found able to enhance significantly doxorubicin cytotoxicity on K562/DOX cells.The results of both pirarubicin uptake and the cytotoxicity assay, indicate that the new compounds of the series are potent P-gp-mediated MDR reversers. They present a structure with a mix of flexible and rigid moieties, a property that seems critical to allow the molecules to choose the most productive of the several binding modes possible in the transporter recognition site.In particular, compounds 5c and 5d, similar to the already reported analogous isomers 1c and 1d,²⁹ are potent and efficacious modulators of P-gp-dependent MDR and may be promising leads for the development of MDR-reversal drugs.     

Hexamers of the Type II Secretion ATPase GspE from Vibrio cholerae with Increased ATPase Activity

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Molecular Basis of Differential Sensitivity of Myeloma Cells to Clinically Relevant Bolus Treatment with Bortezomib

The proteasome inhibitor bortezomib (Velcade) is prescribed for the treatment of multiple myeloma. Clinically achievable concentrations of bortezomib cause less than 85% inhibition of the chymotrypsin-like activity of the proteasome, but little attention has been paid as to whether in vitro studies are representative of this level of inhibition. Patients receive bortezomib as an intravenous or subcutaneous bolus injection, resulting in maximum proteasome inhibition within one hour followed by a gradual recovery of activity. In contrast, most in vitro studies use continuous treatment so that activity never recovers. Replacing continuous treatment with 1 h-pulse treatment increases differences in sensitivity in a panel of 7 multiple myeloma cell lines from 5.3-fold to 18-fold, and reveals that the more sensitive cell lines undergo apoptosis at faster rates. Clinically achievable inhibition of active sites was sufficient to induce cytotoxicity only in one cell line. At concentrations of bortezomib that produced similar inhibition of peptidase activities a different extent of inhibition of protein degradation was observed, providing an explanation for the differential sensitivity. The amount of protein degraded per number of active proteasomes correlated with sensitivity to bortezomib. Thus, (i) in vitro studies of proteasome inhibitors should be conducted at pharmacologically achievable concentrations and duration of treatment; (ii) a similar level of inhibition of active sites results in a different extent of inhibition of protein breakdown in different cell lines, and hence a difference in sensitivity.     

Chromosome Painting in Three Species of Buteoninae: A Cytogenetic Signature Reinforces the Monophyly of South American Species

Buteoninae (Falconiformes, Accipitridae) consist of the widely distributed genus Buteo, and several closely related species in a group called “sub-buteonine hawks”, such as Buteogallus, Parabuteo, Asturina, Leucopternis and Busarellus, with unsolved phylogenetic relationships. Diploid number ranges between 2n = 66 and 2n = 68. Only one species, L. albicollis had its karyotype analyzed by molecular cytogenetics. The aim of this study was to present chromosomal analysis of three species of Buteoninae: Rupornis magnirostris, Asturina nitida and Buteogallus meridionallis using fluorescence in situ hybridization (FISH) experiments with telomeric and rDNA probes, as well as whole chromosome probes derived from Gallus gallus and Leucopternis albicollis. The three species analyzed herein showed similar karyotypes, with 2n = 68. Telomeric probes showed some interstitial telomeric sequences, which could be resulted by fusion processes occurred in the chromosomal evolution of the group, including the one found in the tassociation GGA1p/GGA6. In fact, this association was observed in all the three species analyzed in this paper, and also in L. albicollis, suggesting that it represents a cytogenetic signature which reinforces the monophyly of Neotropical buteoninae species.     

Estimating Encounter Rates and Densities of Three Lemur Species in Northeastern Madagascar

Primate populations, including Madagascar’s lemurs, are threatened worldwide and conservationists need accurate population estimates to develop targeted conservation plans. We sought to fill knowledge gaps for three lemur taxa —white-fronted brown lemur (Eulemur albifrons); eastern woolly lemur (Avahi laniger); and Allocebus/Microcebus, a category combining observations of hairy-eared dwarf lemurs (Allocebus trichotis) and mouse lemurs (Microcebus spp.)— in northeastern Madagascar by estimating their density, examining how their encounter rates and densities vary across three different forest types, and monitoring trends in encounter rates and densities at resurveyed sites, using data from surveys at six forest sites over a 4-year period (2010–2013). Landscape density for white-fronted brown lemur, eastern woolly lemur, and Allocebus/Microcebus was 21.5 (SE 3.67), 57.7 (SE 9.17), and 39.1 (SE 9.55) individuals/km², respectively. There was no difference in density estimates at intact and intermediately degraded forest sites; however, we encountered white-fronted brown lemurs more often in intact forest (1.64 ± SE 0.40 individuals/km) than in intermediately degraded and degraded forest (0.15 ± SE 0.06 and 0.16 ± SE 0.06 individuals/km). In addition, we encountered white-fronted brown lemurs at lower rates in 2013 (0.15 ± SE 0.06 individuals/km) compared to 2010 (0.82 ± SE 0.12 individuals/km) at a resurveyed site. Our findings emphasize that primate researchers must account for variation in how lemur encounter rates and densities differ between intact and degraded forests, and although we observed a decline in white-fronted brown lemur encounter rate at our resurveyed site, we caution that changes in lemur encounter rates may simply reflect lower detection rates rather than lower density. Future research should focus on using conventional distance sampling techniques, which are infrequently used in primate studies, to provide more robust density estimates as a way to accurately assess trends and the effects of anthropogenic pressures on lemur populations.     

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Tissue‐resident memory T (T_RM) cells are abundant in the memory T cell pool and remain resident in peripheral tissues, such as the skin, where they act as alarm sensors or cytotoxic killers. T_RM cells persist long after the pathogen is eliminated and can respond rapidly upon reinfection with the same antigen. When aberrantly activated, skin‐located T_RM cells have a profound role in various skin disorders, including vitiligo and melanoma. Autoreactive T_RM cells are present in human lesional vitiligo skin and mouse models of vitiligo, which suggests that targeting these cells could be effective as a durable treatment strategy for vitiligo. Furthermore, emerging evidence indicates that induction of melanoma‐reactive T_RM cells is needed to achieve effective protection against tumor growth. This review highlights seminal reports about skin‐resident T cells, focusing mainly on their role in the context of vitiligo and melanoma, as well as their potential as therapeutic targets in both diseases.