Deciphering translocations from relicts in Baranof Island mountain goats: is an endemic genetic lineage at risk?

Human-mediated movement of wildlife is a common practice in North America. Some translocations have occurred where local populations were thought to be extinct or simply not present. In Alaska’s Alexander Archipelago, mountain goats (Oreamnos americanus) were not considered indigenous and were introduced to Baranof Island in 1923. However, a range-wide survey using microsatellites and mitochondrial DNA revealed a distinct genetic subpopulation endemic to the island. In this study, we attempted to clarify the evolutionary history of the mountain goats on Baranof Island by examining sequence variation in the Y chromosome. We first screened five regions of the Y chromosome in a subset of mountain goats from across their native range. We detected a single polymorphic site in the SRY promoter, and subsequently sequenced this gene in 100 mountain goats. A unique Y chromosome polymorphism was restricted to Baranof Island and an area near Haines, Alaska, and not detected in the presumed source population. An island-to-mainland dispersal scenario from a cryptic refugial population during the retreat of the Cordilleran ice-sheet would account for this distribution. Overall, these data support the hypothesis that a glacial relict population of mountain goats was present on the island prior to introduction. Based on a combination of mitochondrial, microsatellite, and Y chromosome data, we recommend recognizing Baranof Island mountain goats as an evolutionary significant unit.     

The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity

COVID-19 outbreak is the biggest threat to human health in recent history. Currently, there are over 1.5 million related deaths and 75 million people infected around the world (as of 22/12/2020). The identification of virulence factors which determine disease susceptibility and severity in different cell types remains an essential challenge. The serine protease TMPRSS2 has been shown to be important for S protein priming and viral entry, however, little is known about its regulation. SPINT2 is a member of the family of Kunitz type serine protease inhibitors and has been shown to inhibit TMPRSS2. Here, we explored the existence of a co-regulation between SPINT2/TMPRSS2 and found a tightly regulated protease/inhibitor expression balance across tissues. We found that SPINT2 negatively correlates with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines and was down-regulated in secretory cells from COVID-19 patients. We validated our findings using Calu-3 cell lines and observed a strong increase in viral load after SPINT2 knockdown, while overexpression lead to a drastic reduction of the viral load. Additionally, we evaluated the expression of SPINT2 in datasets from comorbid diseases using bulk and scRNA-seq data. We observed its down-regulation in colon, kidney and liver tumors as well as in alpha pancreatic islets cells from diabetes Type 2 patients, which could have implications for the observed comorbidities in COVID-19 patients suffering from chronic diseases.     

HOT SPOTS OF GENETIC DIVERSITY DESCENDED FROM MULTIPLE PLEISTOCENE REFUGIA IN AN ALPINE UNGULATE

Species that inhabit naturally fragmented environments are expected to be spatially structured and exhibit reduced genetic diversity at the periphery of their range. Patterns of differentiation may also reflect historical processes such as recolonization from glacial refugia. We examined the relative importance of these factors in shaping the spatial patterns of genetic differentiation across the range of an alpine specialist, the North American mountain goat (Oreamnos americanus). Contrary to fossil evidence that suggests a single southern refugium, we detected evidence for additional refugia in northern British Columbia and the Alaskan coast using both mitochondrial and microsatellite DNA. A core area of elevated genetic diversity characterized both regions, and molecular dating suggested a recent Pleistocene split was followed by demographic expansion. Across their range, mountain goats were highly genetically structured and displayed the expected pattern of declining diversity toward the periphery. Gene flow was high within contiguous mountain ranges, but cross‐assignments paradoxically suggest that long‐distance contemporary dispersal movements are not uncommon. These results improve our understanding of how historical vicariance and contemporary fragmentation influence population differentiation, and have implications for conserving the adaptive potential of alpine populations and habitat.     

Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics

Background

Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor side-effects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, α-flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat.

Methods and Findings

The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that α-flupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN). Furthermore, α-flupentixol induced an increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs) after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by α-flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by α-flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion, α-flupentixol failed to induce EPS and to alter STN neuronal activity.

Conclusion

Our study reports strong evidence to show that hypokinesia and catalepsy induced by α-flupentixol are triggered by dramatic changes occurring in basal ganglia network. We provide new insight into the key role of GP in the pathophysiology of APD-induced EPS suggesting that the GP can be considered as a potential target for the treatment of EPS.     

Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling

Introduction  

Subchondral bone alterations represent an essential component of osteoarthritis (OA). Modifying the abnormal subchondral bone metabolism may be indicated to treat OA. We investigated the effect of diacerein and rhein on the changes occurring in subchondral bone during OA. To this end, we determined the drugs' effects on metalloprotease-13 (MMP-13) synthesis on subchondral bone and on the osteoblast signalling pathways. In osteoclasts, we studied MMP-13 and cathepsin K production as well as cell differentiation, proliferation, and survival.     

Is Territory Defence related to Plumage Ornaments in the King Penguin Aptenodytes patagonicus?

Colourful ornaments in monogamous birds may be directed at potential mates or other conspecifics to signal individual condition, reproductive status or fighting ability, especially in monogamous and territorial species. We investigated whether the size of the orange auricular patch may be an indicator of aggressiveness in the king penguin Aptenodytes patagonicus , a monogamous and territorial seabird. The relationship between auricular patch size and defence behaviour was explored relative to territory location (centre vs. periphery of the colony), period of reproduction (early vs. late), state of reproduction (incubation vs. brooding) and sex. The proportion of time spent in territorial defence and the rate of aggressive behaviours were positively correlated with auricular patch size, mainly because central birds were more aggressive than peripheral birds and also had larger patch sizes. The period of reproduction, state of reproduction and sex did not interact with patch size to affect aggressiveness. Our results suggest that the size of the auricular patch in king penguins may be a reliable signal allowing individuals to evaluate the quality of mates or competitors in terms of aggressiveness. Whether aggressiveness is directly linked to patch size or indirectly through body condition, however, remains to be determined. In any event, birds with larger patches seem to gain central territories in the colony, thereby increasing their reproductive success. Finally, our study adds to the growing evidence that the evolution of sexually monomorphic ornaments may stem from mutual sexual selection.