Concerted and Independent Evolution of Control Regions 1 and 2 of Water Monitor Lizards (Varanus salvator macromaculatus) and Different Phylogenetic Informative Markers

Duplicate control regions (CRs) have been observed in the mitochondrial genomes (mitogenomes) of most varanids. Duplicate CRs have evolved in either concerted or independent evolution in vertebrates, but whether an evolutionary pattern exists in varanids remains unknown. Therefore, we conducted this study to analyze the evolutionary patterns and phylogenetic utilities of duplicate CRs in 72 individuals of Varanus salvator macromaculatus and other varanids. Sequence analyses and phylogenetic relationships revealed that divergence between orthologous copies from different individuals was lower than in paralogous copies from the same individual, suggesting an independent evolution of the two CRs. Distinct trees and recombination testing derived from CR1 and CR2 suggested that recombination events occurred between CRs during the evolutionary process. A comparison of substitution saturation showed the potential of CR2 as a phylogenetic marker. By contrast, duplicate CRs of the four examined varanids had similar sequences within species, suggesting typical characteristics of concerted evolution. The results provide a better understanding of the molecular evolutionary processes related to the mitogenomes of the varanid lineage.

Along the Bos Taurus genome, uncover candidate Imprinting Control Regions

In mammals, Imprinting Control Regions (ICRs) regulate a subset of genes in a parent-of-origin-specific manner. In both human and mouse, previous studies identified a set of CpG-rich motifs that occurred as clusters in ICRs and germline Differentially Methylated Regions (gDMRs). These motifs consist of the ZFP57 binding site (ZFBS) overlapping a subset of MLL binding units known as MLL morphemes. Furthermore, by creating plots for displaying the density of these overlaps, it became possible to locate known and candidate ICRs in mouse and human genomic DNA. Since genomic imprinting impacts many developmental and key physiological processes, we performed genome-wide analyses to create plots displaying the density of the CpG-rich motifs (ZFBS-morph overlaps) along Bos Taurus chromosomal DNA. We tailored our datasets so that they could be displayed on the UCSC genome browser (the build bosTau8). On the genome browser, we could view the ZFP57 binding sites, the ZFBS-morph overlaps, and peaks in the density-plots in the context of cattle RefSeq Genes, Non-Cow RefSeq Genes, CpG islands, and Single nucleotide polymorphisms (SNPs). Our datasets revealed the correspondence of peaks in plots to known and deduced ICRs in Bos Taurus genomic DNA. We illustrate that by uploading our datasets onto the UCSC genome browser, we could discover candidate ICRs in cattle DNA. In enlarged views, we could pinpoint the genes in the vicinity of candidate ICRs and thus discover potential imprinted genes.

Language distance modulates cognitive control in bilinguals

Linguistic processes in the bilingual brain are partially shared across languages, and the degree of neural overlap between the languages is influenced by several factors, including the age of acquisition, relative language proficiency, and immersion. There is limited evidence on the role of linguistic distance on the performance of the language control as well as domain-general cognitive control systems. The present study aims at exploring whether being bilingual in close and distant language pairs (CLP and DLP) influences language control and domain-general cognitive processes. We recruited two groups of DLP (Persian–English) and CLP (French–English) bilinguals. Subjects performed language nonswitching and switching picture-naming tasks and a nonlinguistic switching task while EEG data were recorded. Behaviorally, CLP bilinguals showed a lower cognitive cost than DLP bilinguals, reflected in faster reaction times both in language switching (compared to nonswitching) and nonlinguistic switching. ERPs showed differential involvement of cognitive control regions between the CLP and DLP groups during linguistic switching vs. nonswitching at 450 to 515 ms poststimulus presentation. Moreover, there was a difference between CLP and DLP groups from 40 to 150 ms in the nonlinguistic task. Our electrophysiological results confirm a stronger involvement of language control and domain-general cognitive control regions in CLP bilinguals.

Can high SARS-CoV-2 adult vaccination rates help protect unvaccinated children? Evidence from a unique rapid mass vaccination campaign

Background: Mass vaccination has the potential to bring the COVID-19 pandemic to a halt by not only protecting individuals who have been vaccinated but also by providing cross-protection to unvaccinated individuals, such as children. However, this indirect protection effect from a vaccinated population onto an unvaccinated group is extremely difficult to observe in real-world situations. Methods: We studied cross-protection to unvaccinated individuals following an unprecedented rapid mass vaccination campaign in Europe. After a large outbreak of B.1.351 (Beta) in the district of Schwaz in Austria, the government offered every adult (16+) citizen of the district a vaccination with BNT162b2 between the 11th and 16th of March 2021. After this week, around 70% of the adult population of Schwaz had received their first dose, which made Schwaz the first widely inoculated region in Europe. The cohort of children under the age of 16 remained entirely unvaccinated (EMA only approved the vaccine for 12-15 year-olds on the 28th of May). This local mass vaccination campaign created a situation in which the vaccination coverage of the adult population sharply differed at the district border of Schwaz, while the coverage of those below the age of 16 remained the exact same. We compared SARS-CoV-2 cases among the adult population as well as children in Schwaz with case numbers of the same age cohorts from control regions. First, we compared Schwaz with a control group of other Austrian districts highly similar to Schwaz in many socio-demographic characteristics as well as in infection spread prior to the mass vaccination campaign. Second, we compared local populations residing along the border of Schwaz which live in the very same geographic area but with different vaccination coverage because they were not included in the vaccination campaign. Interpretation: Prior the mass vaccination campaign, we observed very similar infection spread across all age cohorts in Schwaz and the control regions. Around 3-4 weeks after the campaign, infections started to diverge between Schwaz and the control regions. While the difference was largest among the population aged 16–50 years (which was offered vaccination in the campaign), we also observed a statistically significant reduction in cases among the group of unvaccinated children. Our findings are robust to changes in the control group, as well as controls of a rich set of time and region specific effects. Policy implications: Our results constitute one of the first evidence of an indirect cross-protection effect from a group of vaccinated individuals to an unvaccinated group (in our case children). Given that in many countries the proposition to keep schools open during the academic year 2021/22 is a top priority, this evidence of community-protection is highly policy relevant.

Assessment of Migration Policy Measures Implemented in the Russian Far East

The present paper analyses migration policy measures implemented in the Russian Far East, namely, State Programme to Assist the Voluntary Resettlement of Compatriots Living Abroad to the Russian Federation, the Far-Eastern Hectare Programme, establishment of Priority Development Areas (PDAs) and territories with a special regime of economic activity. The synthetic control method was applied to quantitatively assess how the adopted measures affect the migration outflow from regions of the Far Eastern Federal District. According to this method and relevant statistics, constituent entities of the Far Eastern Federal District were compared with control regions of the Siberian Federal District, where these policy tools have not been introduced. Comparable areas had similar socio-economic development trends and migration flows in the period preceding the implementation of the state programmes. To analyse the impact of migration policy changes in 2011–2018, the difference between outflow values of the Far Eastern and synthetic control regions was calculated. The results showed that the average estimated values are negative and significantly different from zero. This indicates a positive effect of new migration mitigation measures on reducing the outflow from the Russian Far East. Future research will separately assess the effectiveness of each migration policy tool implemented in the Far Eastern Federal District.

Mitogenomes of Accipitriformes and Cathartiformes Were Subjected to Ancestral and Recent Duplications Followed by Gradual Degeneration

The rearrangement of 37 genes with one control region, firstly identified in Gallus gallus mitogenome, is believed to be ancestral for all Aves. However, mitogenomic sequences obtained in recent years revealed that many avian mitogenomes contain duplicated regions that were omitted in previous genomic versions. Their evolution and mechanism of duplication are still poorly understood. The order of Accipitriformes is especially interesting in this context because its representatives contain a duplicated control region in various stages of degeneration. Therefore, we applied an appropriate PCR strategy to look for duplications within the mitogenomes of the early diverged species Sagittarius serpentarius and Cathartiformes, which is a sister order to Accipitriformes. The analyses revealed the same duplicated gene order in all examined taxa and the common ancestor of these groups. The duplicated regions were subjected to gradual degeneration and homogenization during concerted evolution. The latter process occurred recently in the species of Cathartiformes as well as in the early diverged lineages of Accipitriformes, that is, Sagittarius serpentarius and Pandion haliaetus. However, in other lineages, that is, Pernis ptilorhynchus, as well as representatives of Aegypiinae, Aquilinae, and five related subfamilies of Accipitriformes (Accipitrinae, Circinae, Buteoninae, Haliaeetinae, and Milvinae), the duplications were evolving independently for at least 14–47 Myr. Different portions of control regions in Cathartiformes showed conflicting phylogenetic signals indicating that some sections of these regions were homogenized at a frequency higher than the rate of speciation, whereas others have still evolved separately.

Focal gamma activity in frontal control regions revealed using intraoperative electrocorticography

How the frontal cortex is anatomically and functionally organized to control cognition remains puzzling. Numerous non-invasive brain imaging studies relate cognitive control to a localized set of frontal regions, part of a wider fronto-parietal network (FPN), that show increases in functional MRI (fMRI) signal during the performance of multiple cognitively demanding tasks. Lesions implicating frontal control regions lead to disorganized behaviour. However, the fMRI BOLD signal is an indirect measure of neuronal activity and represents evidence from a single modality. This has led to limited clinical translation of fMRI findings e.g. to guide the surgical resection of brain tumours. Here we sought supporting evidence for lateral frontal control regions using electrocorticography (ECoG). We recorded electrophysiological activity from electrodes placed on the lateral frontal cortex in patients undergoing awake craniotomy for glioma resection. During surgery, patients performed two verbal executive-related counting tasks with a difficulty level manipulation, closely adapting difficulty manipulations in fMRI studies of cognitive control. We performed spectral analysis focusing on the gamma range (30-250 Hz) due to mounting evidence of its value as an index of local cortical processing. Comparing hard versus easy demands revealed circumscribed frontal regions with power increases in the gamma range. This contrasted with spatially distributed power decreases in the beta range (12-30 Hz). Further, electrodes showing significant gamma power increases were more likely to occur within a canonical fMRI-defined FPN and showed stronger gamma power increases compared to electrodes outside the FPN, even at the single patient level. Reinforcing the need for careful task manipulation, an easy versus baseline comparison, which includes factors such as speech output, produced gamma changes over a wider area. Thus, using similar task difficulty manipulations, ECoG and fMRI signals converged on delineating lateral frontal control regions. These findings open the door for extending clinical functional mapping to the domain of cognitive control during awake neurosurgery.

Volume changes of thalamus, hippocampus and cerebellum are associated with specific CSF profile in MS

Background: The underlying pathogenesis of surface-in grey matter abnormalities in MS, demonstrated by both neuropathology and advanced MRI analyses, is under investigation and it might be related to CSF-mediated mechanism of inflammation and/or damage. Objective: To examine the link of CSF inflammatory profile with the damage of three regions early-involved in MS and bordering with CSF: thalamus, hippocampus and cerebellum. Methods: In this longitudinal, prospective study, we evaluated, in 109 relapsing–remitting MS patients, at diagnosis and after 2-year follow-up, the association between the baseline CSF level of 19 inflammatory mediators and the volume changes of thalamus, hippocampus, cerebellar cortex and control regions (globus pallidus, putamen). Results: The multivariable analysis showed that the CXCL13 and sCD163 CSF levels at baseline were independent predictors of thalamus ([Formula: see text]; p < 0.001) and hippocampus ([Formula: see text]; p < 0.001) volume change after 2-year follow-up. These molecules, plus CCL25, IFN-γ and fibrinogen, were independent predictors of the cerebellar cortex volume loss ([Formula: see text]; p < 0.001). No independent predictors of volume changes of the control regions were found. Conclusion: Our results indicate an association between the CSF inflammatory profile and grey matter volume loss of regions anatomically close to CSF boundaries, thus supporting the hypothesis of a surface-in GM damage in MS.