Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation.

Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. Overexpression of MELK enhances (whereas knockdown diminishes) the ability to generate neurospheres from MNPs, indicating a function in self-renewal. MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)-positive progenitors in vitro. MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation. These findings indicate that MELK is necessary for proliferation of embryonic and postnatal MNP and suggest that it regulates the transition from GFAP-expressing progenitors to rapid amplifying progenitors in the postnatal brain

Worshipping with the U.S. Flag

For generations, a silent symbol of politics in U.S. religious congregations has been the presence of the national flag in worship spaces. Despite debates over the flag, there is limited empirical research on its contemporary prevalence or influence in congregations. Building upon research on social sorting, we hypothesize that people with conservative religion and conservative politics sort into congregations displaying the flag. Additionally, we hypothesize a priming effect whereby worshipping with the U.S. flag elevates support for Christian nationalism. Findings from the 2021 Baylor Religion Survey reveal that nearly half of religiously affiliated U.S. adults worship with the flag, most notably members of white Protestant religious traditions (more so than Catholics) and older adults. Regardless of religious tradition or political ideology, worshipping with the flag is associated with support for Christian nationalist beliefs. These finding highlight a sorting process into American congregations and hint at political socialization occurring within them

MYT1L is required for suppressing earlier neuronal development programs in the adult mouse brain

In vitro studies indicate the neurodevelopmental disorder gene myelin transcription factor 1-like (MYT1L) suppresses non-neuronal lineage genes during fibroblast-to-neuron direct differentiation. However, MYT1L\u27s molecular and cellular functions in the adult mammalian brain have not been fully characterized. Here, we found that MYT1L loss leads to up-regulated deep layer (DL) gene expression, corresponding to an increased ratio of DL/UL neurons in the adult mouse cortex. To define potential mechanisms, we conducted Cleavage Under Targets & Release Using Nuclease (CUT&RUN) to map MYT1L binding targets and epigenetic changes following MYT1L loss in mouse developing cortex and adult prefrontal cortex (PFC). We found MYT1L mainly binds to open chromatin, but with different transcription factor co-occupancies between promoters and enhancers. Likewise, multiomic data set integration revealed that, at promoters, MYT1L loss does not change chromatin accessibility but increases H3K4me3 and H3K27ac, activating both a subset of earlier neuronal development genes as well a

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

MYT1L deficiency impairs excitatory neuron trajectory during cortical development

Mutations reducing the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. MYT1L is used as a pro-neural factor in fibroblast-to-neuron transdifferentiation and is hypothesized to influence neuronal specification and maturation, but it is not clear which neuron types are most impacted by MYT1L loss. In this study, we profile 412,132 nuclei from the forebrains of wild-type and MYT1L-deficient mice at three developmental stages: E14 at the peak of neurogenesis, P1 when cortical neurons have been born, and P21 when neurons are maturing, to examine the role of MYT1L levels on neuronal development. MYT1L deficiency disrupts cortical neuron proportions and gene expression, primarily affecting neuronal maturation programs. Effects are mostly cell autonomous and persistent through development. While MYT1L can both activate and repress gene expression, the repressive effects are most sensitive to haploinsufficiency, likely mediating MYT1L syndrome. These findings illuminate MYT1L\u27s role in orchestrating gene expression during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3

Programmable Ligand Detection System in Plants through a Synthetic Signal Transduction Pathway

There is an unmet need to monitor human and natural environments for substances that are intentionally or unintentionally introduced. A long-sought goal is to adapt plants to sense and respond to specific substances for use as environmental monitors. Computationally re-designed periplasmic binding proteins (PBPs) provide a means to design highly sensitive and specific ligand sensing capabilities in receptors. Input from these proteins can be linked to gene expression through histidine kinase (HK) mediated signaling. Components of HK signaling systems are evolutionarily conserved between bacteria and plants. We previously reported that in response to cytokinin-mediated HK activation in plants, the bacterial response regulator PhoB translocates to the nucleus and activates transcription. Also, we previously described a plant visual response system, the de-greening circuit, a threshold sensitive reporter system that produces a visual response which is remotely detectable and quantifiable.We describe assembly and function of a complete synthetic signal transduction pathway in plants that links input from computationally re-designed PBPs to a visual response. To sense extracellular ligands, we targeted the computational re-designed PBPs to the apoplast. PBPs bind the ligand and develop affinity for the extracellular domain of a chemotactic protein, Trg. We experimentally developed Trg fusions proteins, which bind the ligand-PBP complex, and activate intracellular PhoR, the HK cognate of PhoB. We then adapted Trg-PhoR fusions for function in plants showing that in the presence of an external ligand PhoB translocates to the nucleus and activates transcription. We linked this input to the de-greening circuit creating a detector plant.Our system is modular and PBPs can theoretically be designed to bind most small molecules. Hence our system, with improvements, may allow plants to serve as a simple and inexpensive means to monitor human surroundings for substances such as pollutants, explosives, or chemical agents

Existing Knowledge, Knowledge Creation Capability, and the Rate of New Product Introduction in High-Technology Firms

A field study of top management teams and knowledge workers from 72 technology firms demonstrated that the rate of new product and service introduction was a function of organization members' ability to combine and exchange knowledge. We tested the following as bases of that ability: the existing knowledge of employees (their education levels and functional heterogeneity), knowledge from member ego networks (number of direct contacts and strength of ties), and organizational climates for risk taking and teamwork

Drivers of risk perceptions about the invasive non-native plant Japanese knotweed in domestic gardens

This is the final version of the article. Available from Springer Verlag via the DOI in this record.How people perceive risks posed by invasive non-native plants (INNP) can influence attitudes and consequently likely influence behavioural decisions. Although some drivers of risk perception for INNP have been identified, research has not determined those for INNP in domestic gardens. This is concerning as domestic gardens are where people most commonly encounter INNP, and where impacts can be particularly acute. Using a survey approach, this study determined the drivers of perceptions of risk of INNP in domestic gardens and which risks most concern people. Japanese knotweed Fallopia japonica, in Cornwall, UK, where it is a problematic INNP in domestic gardens, was used as a case study. Possible drivers of risk were chosen a priori based on variables previously found to be important for environmental risks. Participants perceived Japanese knotweed to be less frequent on domestic property in Cornwall if their occupation involved the housing market, if they had not had Japanese knotweed in their own garden, if they did not know of Japanese knotweed within 5 km of their home, or if they were educated to degree level. Participants who thought that the consequences of Japanese knotweed being present on domestic property could be more severe had occupations that involved the housing market, knew of Japanese knotweed within 5 km of their home, or were older. Although concern about the damage Japanese knotweed could do to the structure of a property was reported as the second highest motivation to control it by the majority of participants, the perception of threat from this risk was rated as relatively low. The results of this study have implications for policy, risk communication, and garden management decisions. For example, there is a need for policy that provides support and resources for people to manage INNP in their local area. To reduce the impact and spread of INNP we highlight the need for clear and accurate risk communication within discourse about this issue. The drivers identified in this study could be used to target awareness campaigns to limit the development of over- or under-inflated risk perceptions.This project was funded as part of the Wildlife Research Co-Operative between the University of Exeter and the Animal and Plant Health Agency