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Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K sub(2P) 5.1 (TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K sub(2P) 5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K sub(2P) 5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K sub(2P) 5.1 knockout (K sub(2P) 5.1 super(-) super(/) super(-)) mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K sub(2P) 5.1 super(-) super(/) super(-) mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K sub(2P) 3.1 and K sub(V) 1.3 seems to counterbalance the deletion of K sub(2P) 5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K sub(2P) 5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K sub(2P) 5.1-targeting drugs.

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data.

Rationale: Lurasidone is a novel antipsychotic drug with potent binding affinity for dopamine D sub(2) and serotonin (5-hydroxytryptamine, 5-HT) sub(2A), 5-HT sub(7), and 5-HT sub(1A) receptors. Previous pharmacological studies have revealed that lurasidone exhibits a preferable profile (potent antipsychotic activity and lower incidence of catalepsy) to other antipsychotic drugs, although the contribution of receptor subtypes to this profile remains unclear. Objectives: To compare target engagements of lurasidone with those of an atypical antipsychotic, olanzapine, we performed evaluation of dopamine D sub(2)/D sub(3) and serotonin 5-HT sub(2A) receptor occupancy in vivo by positron emission tomography (PET) with conscious common marmosets. Methods: We measured brain receptor occupancies in conscious common marmosets after oral administrations of lurasidone or olanzapine by PET with [ super(11)C]raclopride and [ super(11)C]R-(+)- alpha -(2,3-dimethoxyphenyl )-1-[2-(4-fluorophenylethyl)]-4-piperidine methanol (MDL 100907) for D sub(2)/D sub(3) and 5-HT sub(2A) receptors, respectively. Results: Increases in brain D sub(2)/D sub(3) receptor occupancies of both lurasidone and olanzapine, which reached >80 % at maximum, were observed in the striatum with significant correlations to plasma drug levels. However, lurasidone showed lower 5-HT sub(2A) receptor occupancy in the frontal cortex within the same dose range, while olanzapine showed broadly comparable 5-HT sub(2A) and D sub(2)/D sub(3) receptor occupancies. Conclusions: Compared with olanzapine, lurasidone preferentially binds to D sub(2)/D sub(3) receptors rather than 5-HT sub(2A) receptors in common marmosets. These results suggest that the contribution of in vivo 5-HT sub(2A) receptor blocking activity to the pharmacological profile of lurasidone might differ from olanzapine in terms of the low risk of extrapyramidal syndrome and efficacy against negative symptoms.

Since the establishment of embryonic stem cells and induced pluripotent stem cells (ESCs/iPSCs), the regenerative medicine utilizing these cells as cell sources has become a center of public attention as a novel strategy of treatment for incurable diseases. Various functional cells differentiated from ESCs/iPSCs are expected to be used for 'cell therapy'. Among the transplantable functional cells differentiated from ESCs/iPSCs, hematopoietic stem cells (HSCs) are considered to be strong candidates of cells for regenerative medicine. Although the transplantation of HSCs derived from human bone marrow, mobilized peripheral blood, and umbilical cord blood is the most common human cellbased therapy applied in clinical settings, their availability for clinical use has often been hampered by both the lack of HLA compatible donor and the number of HSCs. We found that the number of hemangioblast colonies significantly increased (3.5 + or - 0.3 %) with the treatment of LY294002. It should be noted that the colony forming cells of hemangioblasts are homogenous; therefore, they might be useful for efficient generation of functional HSCs and EPCs for future regenerative medicine.

Aim Parapatric distributional patterns can arise from abiotic or biotic factors, or from dispersal barriers. Climate change can potentially affect parapatry by changing species’ potential geographic distribution, and thereby widening or shrinking contact zones. Here, we study the effects of climate change on all six species in the genus Callithrix, a group of small‐sized Neotropical primates that is distributed parapatrically in eastern Brazil, allegedly due to biotic interactions. Location Atlantic Forest, savanna and xeric shrublands from Brazil. Methods We explore a method to investigate potential effects of climate change on the distribution of parapatric species by (a) determining whether the parapatric pattern is explained by abiotic (climate) or biotic (species’ interactions) factors using niche equivalency and niche similarity tests; (b) estimating each species’ potential distribution under current and future climatic conditions, using ecological niche models; and (c) performing a pixel‐by‐pixel analysis in order to constrain distribution overlap between species pairs in which parapatry is maintained by biotic factors. Results We found that parapatry in Callithrix is maintained mostly by abiotic factors, except for two species pairs (Callithrix aurita vs. C. flaviceps and C. geoffroyi vs. C. penicillata) in which biotic factors are more likely to be acting. Our proposed method is able to produce better models than conventional ecological niche modelling, predicting net reductions in distribution area for some species and increases for others; however, reductions generally exceeded expansions. The reduction in potential distribution areas would maintain Callithrix flaviceps as Endangered under IUCN criteria. Main conclusions Despite range contractions and the loss of area of sympatry, climate change is unlikely to affect the parapatric distribution patterns in Callithrix, nor intensify interspecific interactions.

We report a preclinical study of a pyrrole-imidazole (PI) polyamide that targets the human transforming growth factor (hTGF)- beta 1 gene as a novel transcriptional gene silencer in a common marmoset primate model. We designed and then synthesized PI polyamides to target the hTGF- beta 1 promoter. We examined effects of seven PI polyamides (GB1101-1107) on the expression of hTGF- beta 1 mRNA stimulated with phorbol 12-myristate 13-acetate (PMA) in human vascular smooth muscle cells. GB1101, GB1105 and GB1106 significantly inhibited hTGF- beta 1 mRNA expression. We examined GB1101 as a PI polyamide to hTGF- beta 1 for hypertrophic scars in marmosets in vivo. Injection of GB1101 completely inhibited hypertrophic scar formation at 35 days post-incision and inhibited cellular infiltration, TGF- beta 1 and vimentin staining, and epidermal thickness. Mismatch polyamide did not affect hypertrophic scarring or histological changes. Epidermis was significantly thinner with GB1101 than with water and mismatch PI polyamides. We developed the PI polyamides for practical ointment medicines for the treatment of hypertrophic scars. FITC-labeled GB1101 with solbase most efficiently distributed in the nuclei of epidermal keratinocytes, completely suppressed hypertropic scarring at 42 days after incision, and considerably inhibited epidermal thickness and vimentin-positive fibroblasts. PI polyamides targeting hTGF- beta 1 promoter with solbase ointment will be practical medicines for treating hypertrophic scars after surgical operations and skin burns.

Consistent inter-individual variation in cognition has been increasingly explored in recent years in terms of its patterns, causes and consequences. One of its possible causes are consistent inter-individual differences in behaviour, also referred to as animal personalities, which are shaped by both the physical and the social environment. The latter is particularly relevant for group-living species like common marmosets ( Callithrix jacchus ), apt learners that display substantial variation in both their personality and cognitive performance, yet no study to date has interlinked these with marmosets’ social environment. Here we investigated (i) consistency of learning speed, and (ii) whether the PCA-derived personality traits Exploration-Avoidance and Boldness-Shyness as well as the social environment (i.e., family group membership) are linked with marmosets’ speed of learning. We tested 22 individuals in series of personality and learning-focused cognitive tests, including simple motor tasks and discrimination learning tasks. We found that these marmosets showed significant inter-individual consistency in learning across the different tasks, and that females learned faster than males. Further, bolder individuals, and particularly those belonging to certain family groups, learned faster. These findings indicate that both personality and social environment affect learning speed in marmosets and could be important factors driving individual variation in cognition.

Animal hybridization is well documented, but evolutionary outcomes and conservation priorities often differ for natural and anthropogenic hybrids. Among primates, an order with many endangered species, the two contexts can be hard to disentangle from one another, which carries important conservation implications. Callithrix marmosets give us a unique glimpse of genetic hybridization effects under distinct natural and human-induced contexts. Here, we use a 44 autosomal microsatellite marker panel to examine genome-wide admixture levels and introgression at a natural C. jacchus and C. penicillata species border along the São Francisco River in NE Brazil and in an area of Rio de Janeiro state where humans introduced these species exotically. Additionally, we describe for the first time autosomal genetic diversity in wild C. penicillata and expand previous C. jacchus genetic data. We characterize admixture within the natural zone as bimodal where hybrid ancestry is biased toward one parental species or the other. We also show evidence that São Francisco River islands are gateways for bidirectional gene flow across the species border. In the anthropogenic zone, marmosets essentially form a hybrid swarm with intermediate levels of admixture, likely from the absence of strong physical barriers to interspecific breeding. Our data show that while hybridization can occur naturally, the presence of physical, even if leaky, barriers to hybridization is important for maintaining species genetic integrity. Thus, we suggest further study of hybridization under different contexts to set well informed conservation guidelines for hybrid populations that often fit somewhere between \"natural\" and \"man-made.\"

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in human with an overall case-fatality rate of >35%. Effective antivirals are crucial for improving the clinical outcome of MERS. Although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. We assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil [MMF], lopinavir/ritonavir, and interferon- beta 1b) in common marmosets with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated and interferon- beta 1b-treated animals had better outcome than the untreated animals, with improved clinical (mean clinical scores [arrowdown]50.9%-95.0% and [arrowdown]weight loss than the untreated animals), radiological (minimal pulmonary infiltrates), and pathological (mild bronchointerstitial pneumonia) findings, and lower mean viral loads in necropsied lung ([arrowdown]0.59-1.06 log10 copies/glyceraldehyde 3-phosphate dehydrogenase [GAPDH]; P < .050) and extrapulmonary ([arrowdown]0.11-1.29 log10 copies/GAPDH; P < .050 in kidney) tissues. In contrast, all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads ([arrowup]0.15-0.54 log10 copies/GAPDH) than the untreated animals. The mortality rate at 36 hours postinoculation was 67% (untreated and MMF-treated) versus 0-33% (lopinavir/ritonavir-treated and interferon- beta 1b-treated). Lopinavir/ritonavir and interferon- beta 1b alone or in combination should be evaluated in clinical trials. MMF alone may worsen MERS and should not be used.

The common marmoset ( Callithrix jacchus ) is increasingly attractive for use as a non-human primate animal model in biomedical research. It has a relatively high reproduction rate for a primate, making it potentially suitable for transgenic modification. Although several attempts have been made to produce non-human transgenic primates, transgene expression in the somatic tissues of live infants has not been demonstrated by objective analyses such as polymerase chain reaction with reverse transcription or western blots. Here we show that the injection of a self-inactivating lentiviral vector in sucrose solution into marmoset embryos results in transgenic common marmosets that expressed the transgene in several organs. Notably, we achieved germline transmission of the transgene, and the transgenic offspring developed normally. The successful creation of transgenic marmosets provides a new animal model for human disease that has the great advantage of a close genetic relationship with humans. This model will be valuable to many fields of biomedical research. Biomedical supermodel: germline transmission in a transgenic non-human primate A non-human primate model amenable to gene manipulation with transgenic technologies would be invaluable for biomedical research into disease mechanisms and for developing therapies in gene therapy and regenerative medicine. An Article published in this issue describes such a model. A team from seven Japanese institutions has generated transgenic nonhuman primates — common marmosets ( Callithrix jacchus ) — in which the integrated transgene is transmitted through the germline and expressed in the offspring. The work involved an enhanced green fluorescent protein (EGFP) transgene, introduced into ten embryos. Four out of five transgenic marmosets expressed EGFP in neonatal tissues; the fifth expressed it in the placenta. Two showed transgene expression in the germ cells, and one fathered a healthy transgenic neonate. The common marmoset is an attractive candidate for transgenic modification, and has potential as a non-human primate animal model in biomedical research. Here, for the first time in non-human primates, an integrated transgene is transmitted through the germ line to the offspring, in which it continues to be expressed.