Estimating human mobility in Holocene Western Eurasia with large-scale ancient genomic data.

The recent increase in openly available ancient human DNA samples allows for large-scale meta-analysis applications. Trans-generational past human mobility is one of the key aspects that ancient genomics can contribute to since changes in genetic ancestry-unlike cultural changes seen in the archaeological record-necessarily reflect movements of people. Here, we present an algorithm for spatiotemporal mapping of genetic profiles, which allow for direct estimates of past human mobility from large ancient genomic datasets.

LC-MS-Based Targeted Metabolomics for FACS-Purified Rare Cells.

Metabolism plays a fundamental role in regulating cellular functions and fate decisions. Liquid chromatography-mass spectrometry (LC-MS)-based targeted metabolomic approaches provide high-resolution insights into the metabolic state of a cell. However, the typical sample size is in the order of 10-10 cells and thus not compatible with rare cell populations, especially in the case of a prior flow cytometry-based purification step.

Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain.

Cortical projection neurons polarize and form an axon while migrating radially. Even though these dynamic processes are closely interwoven, they are regulated separately-the neurons terminate their migration when reaching their destination, the cortical plate, but continue to grow their axons. Here, we show that in rodents, the centrosome distinguishes these processes.

Arc-driven mGRASP highlights CA1 to CA3 synaptic engrams.

Subpopulations of neurons display increased activity during memory encoding and manipulating the activity of these neurons can induce artificial formation or erasure of memories. Thus, these neurons are thought to be cellular engrams. Moreover, correlated activity between pre- and postsynaptic engram neurons is thought to lead to strengthening of their synaptic connections, thus increasing the probability of neural activity patterns occurring during encoding to reoccur at recall.

Moderating role of sociodemographic factors in parental psychiatric treatment before and after offspring severe self-harm.

Background: Parental psychiatric disorders are known risk factors for adolescent self-harm. Although this association is likely to have a bidirectional element, evidence on changes in parental psychiatric treatment following offspring self-harm is scarce.

Methods: Finnish children born in 1987-1996 with a hospital-treated episode of self-harm between the ages 13 and 19 years (N = 3636) were identified using administrative register data, and their biological mothers (N = 3432) and fathers (N = 3167) were followed two years before and after the episode.

Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication.

Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "cap snatching." We report that RNA modification of the cap portion by host 2'-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from , called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its -adenosyl-l-methionine binding pocket to restrict influenza virus replication.

Does Electrophysiological Maturation Shape Language Acquisition?

Infants master temporal patterns of their native language at a developmental trajectory from slow to fast: Shortly after birth, they recognize the slow acoustic modulations specific to their native language before tuning into faster language-specific patterns between 6 and 12 months of age. We propose here that this trajectory is constrained by neuronal maturation-in particular, the gradual emergence of high-frequency neural oscillations in the infant electroencephalogram. Infants' initial focus on slow prosodic modulations is consistent with the prenatal availability of slow electrophysiological activity (i.

Multimodal predictions of treatment outcome in major depression: A comparison of data-driven predictors with importance ratings by clinicians.

Background: Reliable prediction models of treatment outcome in Major Depressive Disorder (MDD) are currently lacking in clinical practice. Data-driven outcome definitions, combining data from multiple modalities and incorporating clinician expertise might improve predictions.

Methods: We used unsupervised machine learning to identify treatment outcome classes in 1060 MDD inpatients.

Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells.

Tissue-intrinsic defense mechanisms eliminate aberrant cells from epithelia and thereby maintain the health of developing tissues or adult organisms. 'Interface surveillance' comprises one such distinct mechanism that specifically guards against aberrant cells which undergo inappropriate cell fate and differentiation programs. The cellular mechanisms which facilitate detection and elimination of these aberrant cells are currently unknown.

Childhood adversity is associated with hospitalisations and survival following external causes and non-communicable diseases: a 46-year follow-up of a Stockholm birth cohort.

Background: Childhood adversity indicated by involvement with child welfare services (ICWS) is associated with increased risks of disease and injuries in young adulthood. It is yet unknown whether such risks are limited to external causes and mental and behavioural disorders or whether they extend beyond early adulthood and to non-communicable diseases (NCDs) with later onset. Moreover, it has not been explored whether ICWS associates with decreased survival prospects following hospitalisation.

Multi-area recordings and optogenetics in the awake, behaving marmoset.

The common marmoset has emerged as a key model in neuroscience. Marmosets are small in size, show great potential for genetic modification and exhibit complex behaviors. Thus, it is necessary to develop technology that enables monitoring and manipulation of the underlying neural circuits.

Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex.

Identification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with decades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a therapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell types and sub-anatomical areas of the human brain this occurs.

Early life climate and adulthood mental health: how birth seasonality influences depressive symptoms in adults.

Background: Early life in-utero can have long-term influence on the mental health status of individuals in adulthood, such as depression. Age, gender, socio-economic status, education, and geography are demographic factors shown to be particularly vulnerable towards the development of depressive symptoms. In addition, climate risks on depression include sunlight, rain, and temperature.

Imaging-Based In Situ Analysis of 5-Methylcytosine at Low Repetitive Single Gene Loci with Transcription-Activator-Like Effector Probes.

Transcription-activator-like effectors (TALEs) are programmable DNA binding proteins that can be used for sequence-specific, imaging-based analysis of cellular 5-methylcytosine. However, this has so far been limited to highly repetitive satellite DNA. To expand this approach to the analysis of coding single gene loci, we here explore a number of signal amplification strategies for increasing imaging sensitivity with TALEs.

District-Level Mortality Convergence in Reunified Germany: Long-Term Trends and Contextual Determinants.

The mortality gap between former East and West Germany decreased rapidly in the decade following the reunification of the country in 1990. However, because no previous study has estimated life expectancy (e0) over time for all German districts, the extent of mortality convergence across districts and its determinants are largely unknown. We used a novel relational Bayesian model to estimate district e0 in Germany during 1997-2016, examined mortality convergence using a novel convergence groups approach, and explored the role of selected district characteristics in the process.

A flexible Bayesian framework for unbiased estimation of timescales.

Timescales characterize the pace of change for many dynamic processes in nature. Timescales are usually estimated by fitting the exponential decay of data autocorrelation in the time or frequency domain. Here we show that this standard procedure often fails to recover the correct timescales due to a statistical bias arising from the finite sample size.

Expression of a Form of Cerebellar Motor Memory Requires Learned Alterations to the Activity of Inhibitory Molecular Layer Interneurons.

Procedural memories formed in the cerebellum in response to motor errors depend on changes to Purkinje cell (PC) spiking patterns that correct movement when the erroneous context is repeated. Because molecular layer interneurons (MLIs) inhibit PCs, learning-induced changes to MLI output may participate in reshaping PC spiking patterns. However, it remains unclear whether error-driven learning alters MLI activity and whether such changes are necessary for the memory engram.

Online neurostimulation of Broca's area does not interfere with syntactic predictions: A combined TMS-EEG approach to basic linguistic combination.

Categorical predictions have been proposed as the key mechanism supporting the fast pace of syntactic composition in language. Accordingly, grammar-based expectations are formed-e.g.

Primary headache disorders in Latin America and the Caribbean: A meta-analysis of population-based studies.

Background: In this manuscript, we aim to systematically estimate the pooled prevalence and incidence of primary headaches and its subtypes (migraine, tension-type headache, and chronic headaches) in Latin America and the Caribbean, describing its epidemiological profile and associated factors.

Methods: We systematically searched PubMed/MEDLINE, Scopus, and LILACS (From conception to March 2021), for populational studies reporting the epidemiology of primary headaches and their associated factors in Latin America and the Caribbean. The data extraction was conducted independently.

Easy efficient HDR-based targeted knock-in in genome using CRISPR-Cas9 system.

During the last two decades, yeast has been used as a biological tool to produce various small molecules, biofuels, etc., using an inexpensive bioprocess. The application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) techniques in yeast genetic and metabolic engineering has made a paradigm shift, particularly with a significant improvement in targeted chromosomal integration using synthetic donor constructs, which was previously a challenge.

AUF-1 knockdown in mice undermines gut microbial butyrate-driven hypocholesterolemia through AUF-1-Dicer-1-mir-122 hierarchy.

Introduction And Objective: Cholesterol homeostasis is a culmination of cellular synthesis, efflux, and catabolism to important physiological entities where short chain fatty acid, butyrate embodied as a key player. This discourse probes the mechanistic molecular details of butyrate action in maintaining host-cholesterol balance.

Methods: Hepatic mir-122 being the most indispensable regulator of cholesterol metabolic enzymes, we studied upstream players of mir-122 biogenesis in the presence and absence of butyrate in Huh7 cells and mice model.

Alterations in rhythmic and non-rhythmic resting-state EEG activity and their link to cognition in older age.

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance.

Spatial and temporal correlations in neural networks with structured connectivity.

Correlated fluctuations in the activity of neural populations reflect the network's dynamics and connectivity. The temporal and spatial dimensions of neural correlations are interdependent. However, prior theoretical work mainly analyzed correlations in either spatial or temporal domains, oblivious to their interplay.

Nightmares and psychiatric symptoms: A systematic review of longitudinal, experimental, and clinical trial studies.

Nightmares occur across a wide range of psychiatric disorders, but outside of PTSD presentations are infrequently considered a treatment priority. We aimed to assess evidence for a contributory causal role of nightmares to the occurrence of psychiatric disorders, and vice versa. A systematic review was conducted of longitudinal, experimental, and clinical trial studies.