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The collection of information on richness and population structure of mammals is essential for their conservation and management. This present study focused on an inventory and populational study of small non-volant mammals (marsupials, shrews, and rodents) from a cloud forest in Yurubi National Park, Venezuela. Conventional traps (snap traps and live traps) were used, together with four pitfall trap systems. Sixteen species of small non-volant mammals from three orders, five families, and 13 genera were recorded. Based on their capture frequencies and high abundances, Nephelomys caracolus, Cryptotis aroensis, Heteromys catopterius and Rhipidomys venustus, endemic species of Venezuela, are the most common in the area. Results suggest that, the park is functioning as an effective biodiversity preserve for small mammals and can maintain their breeding populations in a highly threatened bioregion. Due to its geographic isolation and high richness of endemic species, this area deserves management and protection programs for its ecosystems, some of them already endangered by human impacts.

Small-eared shrews of the New World genus Cryptotis (Eulipotyphla, Soricidae) comprise at least 42 species that traditionally have been partitioned among four or more species groups based on morphological characters. The Cryptotis mexicana species group is of particular interest, because its member species inhibit a subtly graded series of forelimb adaptations that appear to correspond to locomotory behaviors that range from more ambulatory to more fossorial. Unfortunately, the evolutionary relationships both among species in the C. mexicana group and among the species groups remain unclear. To better understand the phylogeny of this group of shrews, we sequenced two mitochondrial and two nuclear genes. To help interpret the pattern and direction of morphological changes, we also generated a matrix of morphological characters focused on the evolutionarily plastic humerus. We found significant discordant between the resulting molecular and morphological trees, suggesting considerable convergence in the evolution of the humerus. Our results indicate that adaptations for increased burrowing ability evolved repeatedly within the genus Cryptotis.

Small-eared shrews of the New World genus Cryptotis (Eulipotyphla, Soricidae) comprise at least 42 species that traditionally have been partitioned among four or more species groups based on morphological characters. The Cryptotis mexicana species group is of particular interest, because its member species inhibit a subtly graded series of forelimb adaptations that appear to correspond to locomotory behaviors that range from more ambulatory to more fossorial. Unfortunately, the evolutionary relationships both among species in the C. mexicana group and among the species groups remain unclear. To better understand the phylogeny of this group of shrews, we sequenced two mitochondrial and two nuclear genes. To help interpret the pattern and direction of morphological changes, we also generated a matrix of morphological characters focused on the evolutionarily plastic humerus. We found significant discordant between the resulting molecular and morphological trees, suggesting considerable convergence in the evolution of the humerus. Our results indicate that adaptations for increased burrowing ability evolved repeatedly within the genus Cryptotis.

Anthropogenic global change is impacting the evolutionary potential of biodiversity in ways that have been difficult to predict. Distinct evolutionary units within species may respond differently to the same environmental trends, reflecting unique geography, ecology, adaptation, or drift. Least shrews (Cryptotis parvus group) have a widespread distribution across North America, yet systematic relationships and ongoing evolutionary processes remain unresolved. Westernmost peripheral populations have been prioritized for conservation, but little is known of their evolutionary histories or population trajectories. The broad range of this group of species is coincident with many other temperate taxa, presenting a hypothesis that diversification of least shrews follows a repeated process through the Pleistocene, leading to regionally diagnosable conservation units. We use genomic data and niche modeling to delimit species and conservation units of least shrews. Our results show that least shrews warrant recognition as multiple distinct species, along with geographically discrete infraspecific lineages of C. parvus (sensu stricto). Western peripheral populations are evolutionarily distinct based on nuclear, but not mitochondrial data, possibly reflecting mitochondrial capture during the last glacial phase. This population represents a relict conservation unit, consistent with both an “adaptive unit” and “management unit” based on non‐neutral and neutral divergence, respectively. Hindcast niche modeling supports growing evidence for a shared process of diversification among co‐distributed biota, and forecast modeling suggests continued future loss of suitable environmental niche in peripheral regions. Given mito‐nuclear discordance among samples of parapatric lineages, future environmental perturbation may continue to impact the genomic integrity of important conservation units, making ecological and genomic monitoring a critical need. Least shrews, distributed widely across North America and Mesoamerica, remain an enigmatic group in terms of their evolutionary history, biogeography, and ongoing responses to environmental change. Under a phylogenomic framework using reduced representation genome data, we investigated these dynamics across multiple scales of analysis. We found that the current taxonomy is in need of revision and provide updated nomenclature, systematic relationships, and conservation implications. This group provides a clear demonstration of diagnosable diversification across this vast study area.

The diversity and distribution of mammals in the American tropics remain incompletely known. We describe a new species of small-eared shrew (Soricidae, Cryptotis) from the Lacandona rain forest, Chiapas, southern Mexico. The new species is distinguished from other species of Cryptotis on the basis of a unique combination of pelage coloration, size, dental, cranial, postcranial, and external characters, and genetic distances. It appears most closely related to species in the Cryptotis nigrescens species group, which occurs from southern Mexico to montane regions of Colombia. This discovery is particularly remarkable because the new species is from a low-elevation habitat (approximately 90 m), whereas most shrews in the region are restricted to higher elevations, typically > 1,000 m. The only known locality for the new shrew is in one of the last areas in southern Mexico where relatively undisturbed tropical vegetation is still found. The type locality is protected by the Mexican government as part of the Yaxchilán Archaeological Site on the border between Mexico and Guatemala. La diversidad y distribución de las musarañas en el trópico americano son, aún, parcialmente conocidas. Aquí presentamos la descripción de una nueva especie de musaraña de orejas cortas (Soricidae, Cryptotis) con base en dos ejemplares de museo colectados en la selva Lacandona, Chiapas, en el sur de Mexico. La nueva especie se puede distinguir de otras especies del género por una combinación de características que incluye la coloración del pelaje, el tamaño, caracteres dentales, craneales, postcraneales y distancias genéticas. El nuevo taxón podría estar relacionado al grupo de especies Cryptotis nigrescens, cuyas especies habitan desde el sur de Mexico hasta las montañas de Colombia. El descubrimiento es particularmente notable ya que la especie nueva habita en tierras bajas (cerca de los 90 m), mientras que la mayoría de las especies en la región están restringidas a elevaciones mayores a los 1000 m. La única localidad para la nueva especie descrita se ubica en la selva Lacandona, una de las últimas áreas al sur de Mexico con vegetación tropical que permanecen sin alterar. La localidad tipo se encuentra en una zona protegida por el gobierno federal mexicano, ya que es parte de la Zona Arqueológica Yaxchilán, ubicada en la frontera entre Mexico y Guatemala.

We studied the taxonomy and biogeography of Mazama bricenii, a brocket deer classified as Vulnerable by the IUCN, drawing on qualitative and quantitative morphology and sequences of the mitochondrial cytochrome-b gene. We used Ecological Niche Modeling (ENM) to evaluate the hypothesis that M. bricenii of the Venezuelan Cordillera de Mérida (CM) might have become isolated from populations of its putative sister species, Mazama rufina, in the Colombian Cordillera Oriental (CO). This hypothesis assumes that warm, dry climatic conditions in the Táchira Depression were unsuitable for the species. Our analyses did not reveal morphological differences between specimens geographically attributable to M. bricenii and M. rufina, and phylogenetic analyses of molecular data recovered M. bricenii nested within the diversity of M. rufina. These results indicate that M. bricenii should be regarded as a junior synonym of M. rufina. ENM analyses revealed the existence of suitable climatic conditions for M. rufina in the Táchira Depression during the last glacial maximum and even at present, suggesting that gene flow between populations in the CO and CM may have occurred until at least the beginning of the current interglacial period and may continue today. Because this pattern might characterize other mammals currently considered endemic to the CM, we examined which of these species match two criteria that we propose herein to estimate if they can be regarded as endemic to the CM with confidence: (1) that morphological or molecular evidence exists indicating that the putative endemic taxon is distinctive from congeneric populations in the CO; and (2) that the putative endemic taxon is restricted to either cloud forest or páramo, or both. Only Aepeomys reigi, Cryptotis meridensis, and Nasuella meridensis matched both criteria; hence, additional research is necessary to assess the true taxonomic status and distribution of the remaining species thought to be CM endemics.

Temsirolimus is a prodrug form of sirolimus (rapamycin). With its analogs (everolimus, ridaforolimus, and rapamycin), it forms a group of anticancer agents that block the activity of one of the two mammalian targets of rapamycin (mTOR) complexes, mTORC1. We investigated the emetic potential of varying doses (0, 0.5, 1, 2.5, 5, 10, 20, and 40 mg/kg, i.p.) of temsirolimus in the least shrew. Temsirolimus caused a bell-shaped and dose-dependent increase in both the mean vomit frequency and the number of shrews vomiting with maximal efficacy at 10 mg/kg ( p < 0.05 and p < 0.02, respectively). Its larger doses (20 or 40 mg/kg) had no significant emetic effect. We also evaluated the emetic potential of its analogs (5, 10, and 20 mg/kg, i.p.), all of which exhibited a similar emetic profile. Our observational studies indicated that temsirolimus can reduce the shrew motor activity at 40 mg/kg, and subsequently, we examined the motor effects of its lower doses. At 10 and 20 mg/kg, it did not affect the spontaneous locomotor activity (distance moved) but attenuated the mean rearing frequency in a U-shaped manner at 10 mg/kg ( p < 0.05). We then determined the broad-spectrum antiemetic potential of a 20 mg/kg (i.p.) dose of temsirolimus against diverse emetogens, including selective and nonselective agonists of 1) dopaminergic D 2/3 receptors (apomorphine and quinpirole); 2) serotonergic 5-HT 3 receptors [5-HT (serotonin) and 2-methyl-5-HT]; 3) cholinergic M 1 receptors (pilocarpine and McN-A-343); 4) substance P neurokinin NK 1 receptors (GR73632); 5) the L-type calcium (Ca 2+ ) channel (LTCC) (FPL64176); 6) the sarcoplasmic endoplasmic reticulum Ca 2+ ATPase inhibitor, thapsigargin; 7) the CB 1 receptor inverse agonist/antagonist, SR141716A; and 8) the chemotherapeutic cisplatin. Temsirolimus prevented vomiting evoked by the aforementioned emetogens with varying degrees. The mechanisms underlying the pro- and antiemetic effects of temsirolimus evaluated by immunochemistry for c-fos expression demonstrated a c-fos induction in the AP and NTS, but not DMNX with the 10 mg/kg emetic dose of temsirolimus, whereas its larger antiemetic dose (20 mg/kg) had no significant effect. Our study is the first to provide preclinical evidence demonstrating the promising antiemetic potential of high doses of temsirolimus and possibly its analogs in least shrews.

The small-eared shrew genus Cryptotis is the third largest in the family Soricidae and occurs in North, Central, and northern South America. In Mexico and Central and South America, most species inhabit geographically isolated moist, montane habitats at middle and high elevations in a typical sky-island pattern. The 49 recognized species have been partitioned into as many as six species groups based on morphological and molecular phylogenetic studies. The relationships among these species groups are poorly resolved, and their evolutionary histories, including migration patterns and locomotor adaptations, remain unclear. Herein, we provide a new phylogeny incorporating complete mitochondrial genomes (mitogenomes) and supermatrix approach. We compared different evolutionary scenarios using approximately unbiased (AU), Kishino-Hasegawa (KH), and Shimodaira-Hasegawa (SH) statistical tests. The phylogenetic hypothesis based on mitogenomes revealed novel relationships supporting a basal position for the Cryptotis parvusgroup in the genus, and a close relationship between C. gracilis and one clade of the C. thomasi-group. The former relationship is consistent with the least derived humerus morphology and northern distribution of the species. The latter relationship implies multiple migrations between Central and South America. The lack of fine resolution for the species group relationships may be due partly to the lack of taxon sampling. In contrast, multi-approach analyses suggest that the unresolved relationships may be a result of rapid diversification during the early stages of Cryptotis evolution.

Subtypes (1–4) of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in the central and peripheral nervous systems, as well as the cells of smooth muscles in many organs. They mainly serve to regulate cellular excitability in these tissues. The HCN channel blocker ZD7288 has been shown to reduce apomorphine-induced conditioned taste aversion on saccharin preference in rats suggesting potential antinausea/antiemetic effects. Currently, in the least shew model of emesis we find that ZD7288 induces vomiting in a dose-dependent manner, with maximal efficacies of 100% at 1 mg/kg (i.p.) and 83.3% at 10 µg (i.c.v.). HCN channel subtype (1–4) expression was assessed using immunohistochemistry in the least shrew brainstem dorsal vagal complex (DVC) containing the emetic nuclei (area postrema (AP), nucleus tractus solitarius and dorsal motor nucleus of the vagus). Highly enriched HCN1 and HCN4 subtypes are present in the AP. A 1 mg/kg (i.p.) dose of ZD7288 strongly evoked c-Fos expression and ERK1/2 phosphorylation in the shrew brainstem DVC, but not in the in the enteric nervous system in the jejunum, suggesting a central contribution to the evoked vomiting. The ZD7288-evoked c-Fos expression exclusively occurred in tryptophan hydroxylase 2-positive serotonin neurons of the dorsal vagal complex, indicating activation of serotonin neurons may contribute to ZD7288-induced vomiting. To reveal its mechanism(s) of emetic action, we evaluated the efficacy of diverse antiemetics against ZD7288-evoked vomiting including the antagonists/inhibitors of: ERK1/2 (U0126), L-type Ca 2+ channel (nifedipine); store-operated Ca 2+ entry (MRS 1845); T-type Ca 2+ channel (Z944), IP 3 R (2-APB), RyR receptor (dantrolene); the serotoninergic type 3 receptor (palonosetron); neurokinin 1 receptor (netupitant), dopamine type 2 receptor (sulpride), and the transient receptor potential vanilloid 1 receptor agonist, resiniferatoxin. All tested antiemetics except sulpride attenuated ZD7288-evoked vomiting to varying degrees. In sum, ZD7288 has emetic potential mainly via central mechanisms, a process which involves Ca 2+ signaling and several emetic receptors. HCN channel blockers have been reported to have emetic potential in the clinic since they are currently used/investigated as therapeutic candidates for cancer therapy related- or unrelated-heart failure, pain, and cognitive impairment.