Chronic maternal depression negatively affects a child’s social engagement, empathy, and development, but an oxytocin-based intervention may be possible.
ObjectiveMaternal depression across the ...postbirth period has long-term negative consequences for infant development. Little is known of the neurobiological underpinnings, but they could involve oxytocin, a neuropeptide that is dysfunctional in depression and is implicated in birth and parenting.MethodThe authors recruited a community cohort of women with high or low depression scores 2 days after childbirth and measured depression again at 6 and 9 months. When the child was 6, the authors evaluated the families of 46 chronically depressed mothers and 103 mothers reporting no depression since childbirth. The child was assessed for psychiatric diagnoses, social engagement, and empathy. Mother, father, and child were tested for salivary oxytocin level and variation in the rs2254298 single nucleotide polymorphism on the OXTR gene.ResultsOf the children of the chronically depressed mothers, 61% displayed axis I disorders, mainly anxiety and oppositional defiant disorder, compared with 15% of the children of nondepressed mothers. In the depressed mothers’ families, salivary oxytocin was lower in mothers, fathers, and children, and the children had lower empathy and social engagement levels. The rs2254298 GG homozygous genotype was overrepresented in depressed mothers and their families, and it correlated with lower salivary oxytocin. Presence of a single rs2254298 A allele (GA or AA genotype) in depressed mothers markedly decreased risk of child psychopathology.ConclusionsThe negative effect of chronic maternal depression on child social outcomes was related to genetic and peripheral biomarkers of the oxytocin system. This suggests a potential for oxytocin-based interventions.
While the series of events that shaped the transition between foraging societies and food producers are well described for Central and Southern Europe, genetic evidence from Northern Europe ...surrounding the Baltic Sea is still sparse. Here, we report genome-wide DNA data from 38 ancient North Europeans ranging from ~9500 to 2200 years before present. Our analysis provides genetic evidence that hunter-gatherers settled Scandinavia via two routes. We reveal that the first Scandinavian farmers derive their ancestry from Anatolia 1000 years earlier than previously demonstrated. The range of Mesolithic Western hunter-gatherers extended to the east of the Baltic Sea, where these populations persisted without gene-flow from Central European farmers during the Early and Middle Neolithic. The arrival of steppe pastoralists in the Late Neolithic introduced a major shift in economy and mediated the spread of a new ancestry associated with the Corded Ware Complex in Northern Europe.
A large body of evidence accumulating in the past few years indicates the physiological significance of non-histone proteins lysine methylation, catalyzed by protein lysine methyl transferases ...(PKMTs). Dysregulation of these enzymes was shown to contribute to the development and progression of numerous diseases. SETD6 lysine methylatransferase was recently shown to participate in essential cellular processes, such as the NFkB pathway, oxidative stress and also the Wnt signaling cascade. In order to test the effect of blocking SETD6 catalytic activity, we used the peptide inhibition method, which is considered highly specific and can potentially target almost any protein. We designed a 15 amino acids peptide based on the sequence of the RelA protein (residues 302-316), containing the lysine that is methylated by SETD6. To enable cellular intake, the designed peptide was fused to a cell penetrating peptide (CPP) vp22. The vp22-RelA302-316 peptide showed direct and specific interaction with SETD6
. This interaction was shown to inhibit SETD6 methyltransferase activity. SETD6 catalytic blockage by the peptide was also observed in cells upon treatment with the vp22-RelA302-316, resulting in induced cellular migration and proliferation. This new insight into the activity of a methylation inhibitory peptide could represent a milestone in the development of therapeutic tools, which can be of use in physiological cases where administration of cell proliferation is required.
Yersinia pestis, the etiologic agent of plague, is a bacterium associated with wild rodents and their fleas. Historically it was responsible for three pandemics: the Plague of Justinian in the 6th ...century AD, which persisted until the 8th century 1; the renowned Black Death of the 14th century 2, 3, with recurrent outbreaks until the 18th century 4; and the most recent 19th century pandemic, in which Y. pestis spread worldwide 5 and became endemic in several regions 6. The discovery of molecular signatures of Y. pestis in prehistoric Eurasian individuals and two genomes from Southern Siberia suggest that Y. pestis caused some form of disease in humans prior to the first historically documented pandemic 7. Here, we present six new European Y. pestis genomes spanning the Late Neolithic to the Bronze Age (LNBA; 4,800 to 3,700 calibrated years before present). This time period is characterized by major transformative cultural and social changes that led to cross-European networks of contact and exchange 8, 9. We show that all known LNBA strains form a single putatively extinct clade in the Y. pestis phylogeny. Interpreting our data within the context of recent ancient human genomic evidence that suggests an increase in human mobility during the LNBA, we propose a possible scenario for the early spread of Y. pestis: the pathogen may have entered Europe from Central Eurasia following an expansion of people from the steppe, persisted within Europe until the mid-Bronze Age, and moved back toward Central Eurasia in parallel with human populations.
•Six Late Neolithic–Early Bronze Age European Y. pestis genomes were reconstructed•All Late Neolithic and Early Bronze Age Y. pestis form a single phylogenetic branch
Andrades Valtueña et al. present the first six European Y. pestis genomes dating from the Late Neolithic and the Early Bronze Age. These data suggest that Y. pestis entered Europe during a human migration around 4800 BP, persisted in Europe, and traveled back to Central Eurasia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Anatolia was home to some of the earliest farming communities. It has been long debated whether a migration of farming groups introduced agriculture to central Anatolia. Here, we report the first ...genome-wide data from a 15,000-year-old Anatolian hunter-gatherer and from seven Anatolian and Levantine early farmers. We find high genetic continuity (~80-90%) between the hunter-gatherers and early farmers of Anatolia and detect two distinct incoming ancestries: an early Iranian/Caucasus related one and a later one linked to the ancient Levant. Finally, we observe a genetic link between southern Europe and the Near East predating 15,000 years ago. Our results suggest a limited role of human migration in the emergence of agriculture in central Anatolia.
The COVID-19 pandemic demonstrated that the process of global vaccination against a novel virus can be a prolonged one. Social distancing measures, that are initially adopted to control the pandemic, ...are gradually relaxed as vaccination progresses and population immunity increases. The result is a prolonged period of high disease prevalence combined with a fitness advantage for vaccine-resistant variants, which together lead to a considerably increased probability for vaccine escape. A spatial vaccination strategy is proposed that has the potential to dramatically reduce this risk. Rather than dispersing the vaccination effort evenly throughout a country, distinct geographic regions of the country are sequentially vaccinated, quickly bringing each to effective herd immunity. Regions with high vaccination rates will then have low infection rates and vice versa. Since people primarily interact within their own region, spatial vaccination reduces the number of encounters between infected individuals (the source of mutations) and vaccinated individuals (who facilitate the spread of vaccine-resistant strains). Thus, spatial vaccination may help mitigate the global risk of vaccine-resistant variants.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Legionella pneumophila and Coxiella burnetii have been shown to utilize the icm/dot type IV secretion system for pathogenesis and recently a large number of icm/dot-translocated substrates were ...identified in L. pneumophila. Bioinformatic analysis has revealed that 13 of the genes encoding for L. pneumophila-translocated substrates and five of the C. burnetii icm/dot genes, contain a conserved regulatory element that resembles the target sequence of the PmrA response regulator. Experimental analysis which included the construction of a L. pneumophila pmrA deletion mutant, intracellular growth analysis, comparison of gene expression between L. pneumophila wild type and the pmrA mutant, construction of mutations in the PmrA conserved regulatory element, controlled expression studies as well as mobility shift assays, demonstrated the direct relation between the PmrA regulator and the expression of L. pneumophila icm/dot-translocated substrates and several C. burnetii icm/dot genes. Furthermore, genomic analysis identified 35 L. pneumophila and 68 C. burnetii unique genes that contain the PmrA regulatory element and few of these genes from L. pneumophila were found to be new icm/dot-translocated substrates. Our results establish the PmrA regulator as a fundamental regulator of the icm/dot type IV secretion system in these two bacteria.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We consider the problem of locating a facility on a network represented by a graph. A set of strategic agents have different ideal locations for the facility; the cost of an agent is the distance ...between its ideal location and the facility. A
mechanism
maps the locations reported by the agents to the location of the facility. We wish to design mechanisms that are
strategyproof
(SP) in the sense that agents can never benefit by lying and, at the same time, provide a small approximation ratio with respect to the
minimax
measure. We design a novel "hybrid" strategyproof randomized mechanism that provides a tight approximation ratio of 3/2 when the network is a circle (known as a
ring
in the case of computer networks). Furthermore, we show that no randomized SP mechanism can provide an approximation ratio better than 2 -
o
(1), even when the network is a tree, thereby matching a trivial upper bound of two.
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BFBNIB, CEKLJ, INZLJ, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, ZRSKP
Remodelling is a fundamental biological process involved in the maintenance of bone physiology and function. We know that a range of health and lifestyle factors can impact this process in living and ...past societies, but there is a notable gap in bone remodelling data for populations from the Pacific Islands. We conducted the first examination of femoral cortical histology in 69 individuals from ca. 440-150 BP Taumako in Solomon Islands, a remote 'Polynesian Outlier' island in Melanesia. We tested whether bone remodelling indicators differed between age groups, and biological sex validated using ancient DNA. Bone vascular canal and osteon size, vascular porosity, and localised osteon densities, corrected by femoral robusticity indices were examined. Females had statistically significantly higher vascular porosities when compared to males, but osteon densities and ratios of canal-osteon (~ 8%) did not differ between the sexes. Our results indicate that, compared to males, localised femoral bone tissue of the Taumako females did not drastically decline with age, contrary to what is often observed in modern populations. However, our results match findings in other archaeological samples-a testament to past female bone physiology resilience, also now observed in the Pacific region.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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