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Background: Family-centered substance use treatment (FCSUT) may have benefits for parents, children, and their families, and have the potential to decrease adverse childhood experiences (ACEs). Few treatment programs use FCSUT, even those that aim to serve pregnant and postpartum people., Objectives: To understand how families are integrated into FCSUT services for pregnant and postpartum people, explore the perceived benefits of FCSUT for families and parents, and identify challenges to implementing FCSUT., Participants and Settings: Interviews with 26 administrators and providers working at FCSUT facilities and 27 pregnant and postpartum people who were currently receiving or had previously received services in the last two years from FCSUT facilities., Methods: A qualitative thematic analysis was conducted using data from semi-structured in-depth interviews., Results: The analysis revealed four themes: (1) the importance of families in treatment and recovery; (2) benefits of FCSUT for parents; (3) benefits of FCSUT for families; and (4) additional areas for FCSUT program growth. Despite reported benefits (e.g., improving parenting and communication skills; promoting healthy relationships with children, partners, and other family members; and facilitating a support system for long-term recovery), facilities and families face challenges integrating whole family units into treatment., Conclusions: FCSUT may offer a range of benefits to pregnant and postpartum people and their families. Addressing challenges, such as fully integrating all family members into treatment, may improve FCSUT programs. Meeting the needs of all family members during treatment supports safe, stable, and nurturing relationships and environments for children that may decrease ACEs., Competing Interests: Declaration of competing interest Funding support for this project was provided by the National Center for Injury Prevention and Control, U.S. Centers for Disease Control and Prevention (CDC) through a contract to Fors Marsh Group, LLC, Contract Number 47QRAD21DU200, OMB Control Numbers 0920-1154 and 0990-0421., (Published by Elsevier Ltd.)

Introduction: Family-centered substance use treatment (FCSUT) approaches for pregnant and postpartum people have the potential to prevent intergenerational transmission of adverse childhood experiences (ACEs). Guided by two theoretical frameworks drawn from implementation science (the Consolidated Framework for Implementation Research [CFIR] and the Reach, Effectiveness, Adoption, Implementation and Maintenance [RE-AIM] framework), this study used a mixed methods approach to answer: (1) What is the extent to which FCSUT approaches are offered for pregnant and postpartum people seeking substance use disorder (SUD) treatment? and (2) How are FCSUT approaches for pregnant and postpartum people implemented?, Methods: This study utilized a sequential mixed methods design that began with quantitative data collection followed by qualitative data collection. The quantitative component consisted of service provision surveys of facilities that provided FCSUT to pregnant and postpartum people (n = 118). The qualitative component consisted of semi-structured in-depth interviews with administrators and providers working at FCSUT facilities (n = 26) and pregnant and postpartum people who were currently receiving or had previously received services in the last two years from FCSUT facilities (n = 27). The qualitative findings were used to deepen understanding of the quantitative findings., Results: Findings from the quantitative survey of treatment facilities' FCSUT provision revealed that while most facilities offered services related to substance use treatment, behavioral health, and parenting skills development or parent training, a smaller proportion offered services related to prenatal and postpartum health, sexual and reproductive health, and family-related services. Qualitative in-depth interviews with program administrators and providers and pregnant and postpartum people who had participated in FCSUT programs revealed major themes around expanding reach of facilities by maintaining participants' familial connections, resources for implementation and maintenance of FCSUT, the importance of program adaptation, and gaps in service delivery., Conclusions: Results indicated there is a wide range of FCSUT services offered at treatment facilities across the United States. Furthermore, while many pregnant and postpartum people expressed positive experiences with FCSUT, there are some areas that should be considered for future progress to be made., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose. Funding support for this project was provided by the National Center for Injury Prevention and Control, U.S. Centers for Disease Control and Prevention (CDC) through a contract to Fors Marsh Group, LLC, Contract Number 47QRAD21DU200, OMB Control Numbers 0920-1154 and 0990-0421. The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Duplications and deletions of short chromosomal fragments are increasingly recognized as the cause for rare neurodevelopmental conditions and disorders. The NDR2 gene encodes a protein kinase important for neuronal development and is part of a microduplication region on chromosome 12 that is associated with intellectual disabilities, autism, and epilepsy. We developed a conditional transgenic mouse with increased Ndr2 expression in postmigratory forebrain neurons to study the consequences of an increased gene dosage of this Hippo pathway kinase on brain circuitry and cognitive functions. Our analysis reveals reduced terminal fields and synaptic transmission of hippocampal mossy fibers, altered hippocampal network activity, and deficits in mossy fiber-dependent behaviors. Reduced doublecortin expression and protein interactome analysis indicate that transgenic Ndr2 disturbs the maturation of granule cells in the dentate gyrus. Together, our data suggest that increased expression of Ndr2 may critically contribute to the development of intellectual disabilities upon gene amplification., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Introduction: The prevalence of e-cigarette use among US adolescents is increasing. However, there is limited research on the prevalence and correlates of e-cigarette use among adolescents in low income and under resourced communities. We report on their e-cigarette susceptibility and use behaviors, and perceived risks of harm and addiction., Methods: Students in grades 7, 9, and 11 from a Title I school district in the northeastern US completed an online survey during a class period. Lifetime e-cigarette use and its correlates were tested in bivariate and logistic regression models., Results: Most students were of Latino ethnicity (66%), and 36% identified as Black/African American. Overall, 55% of the full sample were considered 'susceptible' to e-cigarette use: 19% were lifetime e-cigarette users while 6% were lifetime smokers. Students in 11th grade were more likely (OR = 2.5) to have ever used e-cigarettes compared to students in 7th grade. Those that were more curious (OR = 11.8), intended to use e-cigarettes in the next 12 months (OR = 2.8), and would use the product if it was offered by a friend (OR = 2.4) had greater odds of lifetime e-cigarette use. By contrast, students who perceived at least moderate risks of health harm (OR = 0.44) were less likely to have used e-cigarettes., Conclusions: Adolescents from marginalized communities are susceptible to and are using e-cigarettes. Prevention efforts targeting underserved areas may benefit from e-cigarette health education messages that reduce curiosity, interrupt social aspects of initiation, and emphasize health harms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

One-on-one peer coaching/support programs hold promise in promoting healthy outcomes among women at risk for and surviving with breast cancer, with the potential to bridge gaps in "whole person care." Although popularly cited for their benefits, emerging evidence is mixed and suggests that peer support program impacts may be attenuated by individual- and community-specific factors. We evaluated a national not-for-profit breast cancer organization's peer support program outcomes (2015-2018) serving women from predominantly Jewish backgrounds to examine program engagement, facilitation, and satisfaction. Of the N = 392 women sampled, 37% utilized the peer support program: the majority were referred by a family member/friend (40%) or had connected with the program online (34%). Logistic regression modeling revealed that mothers (odds ratio [OR] = 1.82; 95% confidence interval [CI] = 1.04 to 3.19), women at increased genetic risk for breast cancer (OR = 2.07; 95% CI = 1.08 to 3.94), and those who connected with the organization through a family member/friend (OR = 1.97; 95% CI = 1.23 to 3.15) were significantly more likely to utilize peer support (all p's < .05). Satisfaction with peer support was high and reliably measured (M = 42.8 out of possible 50; α = .95). These findings emphasize opportunities for peer support programs to serve a range of needs among breast cancer previvors and survivors and increase health care's organizational capacity to reach and impact this community through trusted and well-trained lay coaches., (© Society of Behavioral Medicine 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Many young adult hookah tobacco users do not consider themselves hookah "smokers," but data on this topic are limited. There are no existing measures of young adults' mental schemas of hookah "smokers." We examined the factor structure and reliability of the Hookah Smoker Scale and examined associations with perceived harm and addictiveness and attitudes toward hookah. Two hundred and forty-six young adult (ages 18-30) hookah smokers participated in a cross-sectional online study. Participants completed items assessing schemas characterizing hookah smokers and valid measures of perceived harm and addictiveness of hookah smoking, risk appraisals, and attitudes toward hookah. Exploratory factor analysis using principal axis factoring with oblique rotation extracted a 12-item scale with three dimensions (Regular Use, Social-Enabled Use, and Self-Enabled Use). The scale explained 69.7% of the variance (eigenvalue = 9.2). Cronbach's α for the scale was .89, with Cronbach's α ≥ .80 for four-item subscales. Higher subscale scores indicate stronger beliefs that the dimension characterizes a hookah smoker. Higher Regular Use scores (score variance = 46.9%; eigenvalue = 5.6) were associated with greater perceived harm and addictiveness (β = 0.21, p = .01), greater risk appraisals (β = 0.20, p = .02), and more negative attitudes toward hookah (β = -0.18, p = .03). The Hookah Smoker Scale is a promising measure that can be used to identify targets for preventing and reducing young adults' hookah tobacco use. Findings also suggest young adults associate health risks of hookah with daily smoking, but not with intermittent social smoking patterns., (© Society of Behavioral Medicine 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hookah tobacco use is common among young adults. Unlike cigarette smoking, there is limited evidence on mobile (ie, mHealth) interventions to promote cessation., Objectives: This pilot study tested the preliminary effects of mobile messaging for cessation in young adult hookah smokers., Methods: Young adults (N = 20) aged 18 to 30 years who smoke hookah at least monthly and have done so at least once in the past 30 days received a 6-week mHealth multimedia messaging (text and images) intervention. Message scheduling (2 days/week × 6 weeks) was based on the literature. Content was developed iteratively by the study team and focused on health harms and addictiveness of hookah. Content was individually tailored by baseline hookah use frequency, risk beliefs, and responses to interactive text messages assessing participants' hookah tobacco use behavior and beliefs to maximize impact. Engagement was assessed during the intervention, and we examined effects on risk perceptions, risk beliefs, and risk appraisals, motivation to quit, and behavior change immediately post-intervention., Results: Participants responded to 11.5 (SD = 0.69) of 12 text message prompts on average, endorsed high message receptivity (M = 6.1, SD = 0.93, range = 1-7), and reported the messages were helpful (M = 8.5, SD = 1.5, range = 1-10). There were significant ( P  < .05) increases in risk perceptions (d's = 0.22-0.88), risk appraisals (d = 0.49), risk beliefs (d = 1.11), and motivation to quit (d = 0.97) post-intervention. Half of participants reported reducing frequency of hookah use (20%) or quitting completely (30%) by end of treatment., Conclusions: These pilot results provide preliminary support for an mHealth messaging intervention about risks of hookah tobacco for promoting cessation. Rigorously examining the efficacy of this promising intervention is warranted., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: Philip Morris International's heated tobacco product, Marlboro IQOS, is available internationally and will soon be marketed in the U.S. We examined correlates of curiosity, interest, and likelihood to use IQOS among U.S. young adults., Methods: Young adults ages 18 - 30 years (N = 346) were recruited online, viewed a description of IQOS, and completed measures of sociodemographic characteristics, perceived risks, curiosity, interest, and likelihood to use IQOS., Results: Males had greater curiosity, interest, and likelihood to use IQOS than females. Individuals with household income of $50,000 - $75,000 were more curious than those with household income of greater than $75,000. Cigarette smokers, e-cigarette and dual users had greater curiosity, interest, and likelihood of use than non-tobacco users. Non-white individuals and older young adults had greater likelihood of use. Greater perceived risks of IQOS were negatively associated with curiosity, interest, and likelihood of use., Conclusions: Among young adults, IQOS has greater appeal among males, non-white individuals, those who are older, those with household income of $50,000-$75,000, cigarette smokers, e-cigarette and dual users, and those with less perceived risks of IQOS. Research on public education communicating the potential risks of IQOS to vulnerable young adults is warranted., Competing Interests: Conflict of Interest Statement All authors of this article declare they have no conflicts of interest.

Objective: We examined effects of hookah tobacco risk messages on risk appraisals, attitudes towards hookah, ambivalence about hookah use, and willingness to smoke in young adults aged 18-30 years ( n = 234)., Design: In an online experiment, participants completed preexposure measures and were randomized to hookah tobacco risk messages or to a no message control condition., Main Outcome Measures: Risk appraisals, attitudes, ambivalence, and willingness to smoke hookah., Results: Those who viewed risk messages reported greater risk appraisals (M 4.50, SD 1.17 vs. M 3.87, SD 1.16, p < .001), less positive attitudes (M -0.56, SD 1.24, vs. M 0.39, SD 1.35, p < .001), greater ambivalence (M 3.86, SD 1.26, vs. M 3.08, SD 1.32, p < .001), and less willingness to smoke than controls (M 4.48, SD 1.27, vs. M 4.85, SD 1.37, p = .034). Structural equation modeling demonstrated messages reduced willingness to smoke by evoking less positive attitudes ( b = -0.15, 95% CI -0.32, -0.05) and by the effect of heightened risk appraisals on less positive attitudes ( b = -0.14, 95% CI -0.30, -0.07)., Conclusions: Honing messages and understanding their mechanisms of action are necessary to produce more effective interventions to address hookah and other tobacco use in young adults., Competing Interests: Disclosure statement No potential conflict of interest was reported by the author(s).

Introduction: The Food and Drug Administration announced intent to reduce the nicotine content in cigarettes. There is limited evidence on how reduced nicotine content cigarette (RNC) marketing affects product beliefs and use, and research on this is needed to inform regulations., Methods: In an online experiment, 426 young adult cigarette smokers (aged 18-30 years) were randomized in a 2 (implicit: red package vs. blue package) × 2 (explicit: corrective message vs. no corrective message) design to view an advertisement for previously commercially available RNCs. Outcomes were advertisement content recall, product beliefs, and use intentions. Participants' responses to open-ended assessment of their beliefs about the stimuli were coded to identify prevailing themes., Results: Red packaging and corrective messaging were independently associated with greater advertisement content recall (p = .01 and p = .04, respectively). There were no significant main or interaction effects on product beliefs or use intentions. Controlling for condition, advertisement content recall was significantly associated with less favorable product beliefs (p < .001) and favorable product beliefs were associated with intent to use the product (p < .001). Open-ended responses converged on the finding that respondents were interested in RNCs, but expressed skepticism about effectiveness and value., Conclusions: Brief exposure to an RNC advertisement with red packaging and corrective messaging were each independently associated with greater advertisement content recall. The results indicate: (1) interest and confusion among young adult smokers regarding RNCs, (2) beliefs about RNCs are influenced by marketing, and (3) beliefs are associated with intention to use RNCs., Implications: Findings from this study demonstrate the importance of advertising effects on beliefs about RNC products and support the need to regulate advertising and labeling alongside product regulation. More detailed study of advertisement features that affect consumers' beliefs about RNCs and how they impact their processing of explicit messaging about product risks will be important to guide regulatory decision-making., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background . Hookah is one of the most commonly used tobacco products among U.S. young adults due in part to widespread misperceptions that it is not harmful or addictive. There is growing evidence that hookah tobacco is associated with health harms and can lead to addiction. Research on interventions to address these misperceptions by communicating the harms and addictiveness of hookah use is needed. Aims . This study developed and pretested mobile multimedia message service (MMS) message content communicating the risks of hookah tobacco use to young adult hookah smokers. Method . Message content, delivery, and pretesting were tailored to participants' risk beliefs, hookah use frequency, and responses to simulated text message prompts. Participants viewed 4 of 12 core MMS messages randomized within-subjects and completed postexposure measures of message receptivity and emotional response (e.g., worry). Results . The sample included 156 young adult (age 18-30 years) hookah smokers; 31% smoked hookah monthly and 69% weekly/daily. Prior to viewing messages, a majority endorsed beliefs reflecting misperceptions about the risks of hookah tobacco. Postexposure measures showed participants were receptive to the messages and the messages evoked emotional response. As anticipated, messages produced similar receptivity and there were few differences in emotional response between the messages tested. Discussion . Young adult hookah tobacco smokers were receptive to tailored mobile MMS messages and messages evoked emotional response, two critical precursors to behavior change. Conclusion . Findings indicate that research testing the efficacy of tailored MMS messaging as a strategy for reducing hookah tobacco use in young adults is warranted.

This report documents the case of a 64-year-old African-American female with new end-stage renal disease (ESRD), diagnosed with systemic lupus erythematosus (SLE) on renal biopsy and serologies including a positive ANA (>1:2560), positive anti-Sm antibodies, low titer anti-RNP antibodies, high titer anti-Ro antibodies, anti-dsDNA antibodies, lupus anticoagulant, and hypocomplementemia. She was also noted to have tender nodules on the bilateral shins. Excisional biopsy of one of the nodules showed marked fat necrosis with "ghost cells" and patchy basophilic granular debris consistent with pancreatic panniculitis. Further examination for pancreatic pathology showed an elevated lipase of 585 U/L (reference range 8-78 U/L) and amylase of 214 U/L (reference range 25-125 U/L). However, computed tomography imaging showed no evidence of pancreatitis or pancreatic tumors. This is very similar to another case recently reported in the literature. Similarities of these two cases (African-American females with lupus nephritis on dialysis) may represent a particular subset of SLE patients at increased risk for pancreatic panniculitis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Understanding the movement of animals is important for a wide range of scientific interests including migration, disease spread, collective movement behaviour and analysing motion in relation to dynamic changes of the environment such as wind and thermal lifts. Particularly, the three-dimensional (3D) spatial-temporal nature of bird movement data, which is widely available with high temporal and spatial resolution at large volumes, presents a natural option to explore the potential of immersive analytics (IA). We investigate the requirements and benefits of a wide range of immersive environments for explorative visualization and analytics of 3D movement data, in particular regarding design considerations for such 3D immersive environments, and present prototypes for IA solutions. Tailored to biologists studying bird movement data, the immersive solutions enable geo-locational time-series data to be investigated interactively, thus enabling experts to visually explore interesting angles of a flock and its behaviour in the context of the environment. The 3D virtual world presents the audience with engaging and interactive content, allowing users to 'fly with the flock', with the potential to ascertain an intuitive overview of often complex datasets, and to provide the opportunity thereby to formulate and at least qualitatively assess hypotheses. This work also contributes to ongoing research efforts to promote better understanding of bird migration and the associated environmental factors at the global scale, thereby providing a visual vehicle for driving public awareness of environmental issues and bird migration patterns.

Purpose: Adolescent and young adult (AYA) cancer survivors experience fertility and childrearing challenges in adulthood, but there is limited evidence on awareness, beliefs, and concerns about oncofertility in this population, needs for supportive resources, and associations with quality of life (QoL)., Methods: Participants were 69 AYAs aged 12-25 who were diagnosed with cancer at age 18 years or younger and ≥1 year cancer free, recruited from childhood cancer clinical records and support organizations. Participants completed self-report assessment of oncofertility knowledge and beliefs, information needs, and measures of QoL. Analyses examined associations between oncofertility-related variables and QoL., Results: Knowledge and beliefs about oncofertility options were considerably low in the sample, and participants reported unmet oncofertility resource needs. In multivariable analyses, QoL was associated with beliefs valuing the importance of fertility in childhood cancer (β = 0.87, p = 0.01) and lower information needs (β = -1.19, p = 0.022)., Conclusions: Infertility is a well-documented effect of childhood cancer treatment. Our findings indicate that clinical providers are a preferred source of information for AYA patients, and there is a need to address oncofertility concerns and challenges in this group. Research is needed to examine barriers to addressing fertility issues in childhood cancer treatment and ways to promote dialogue between providers and patients and their families.

The serine/threonine kinase Ndr2 has been shown to control the inside-out activation of the β 1 subunit of integrins and the formation of neurites in both primary neurons and neurally differentiated pheochromacytoma (PC12) cells. In this study, we demonstrate that Ndr2 kinase furthermore determines the substrate specificity of neurite extension in PC12 cells via expression of α 1 β 1 integrins. We show that stable overexpression of Ndr2 in PC12 cells increases neurite growth and extension on poly-D-lysine substrate, likely involving an increased expression of active β 1 integrin in the growth tips of these cells. By contrast, the Ndr2 overexpressing cells do not show the α 1 β 1 integrin-mediated enhancement of neurite growth on collagen IV substrate that can be seen in control cells. Moreover, they entirely fail to increase in response to activation of α 1 β 1 integrins via a soluble KTS ligand and show a diminished accumulation of α 1 integrin in neurite tips, although the expression of this subunit is induced during differentiation to comparable levels as in control cells. Finally, we demonstrate that Ndr2 overexpression similarly inhibits the α 1 β 1 integrin-dependent dendritic growth of primary hippocampal neurons on laminin 111 substrate. By contrast, lack of Ndr2 impairs the dendritic growth regardless of the substrate. Together, these results suggest that Ndr2 regulates α 1 integrin trafficking in addition to β 1 integrin subunit activation and thereby controls the neurite growth on different extracellular matrix (ECM) substrates.

Objective: Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy characterized by auditory symptoms. Two genes, LGI1 and RELN, encoding secreted proteins, are implicated in the etiology of ADLTE, but half of the affected families remain genetically unsolved, and the underlying molecular mechanisms are yet to be clarified. We aimed to identify additional genes causing ADLTE to better understand the genetic basis and molecular pathway underlying this epileptic disorder., Methods: A cohort of Italian ADLTE families was examined by whole exome sequencing combined with genome-wide single-nucleotide polymorphism-array linkage analysis., Results: We identified two ADLTE-causing variants in the MICAL-1 gene: a p.Gly150Ser substitution occurring in the enzymatically active monooxygenase (MO) domain and a p.Ala1065fs frameshift indel in the C-terminal domain, which inhibits the oxidoreductase activity of the MO domain. Each variant segregated with ADLTE in a single family. Examination of candidate variants in additional genes excluded their implication in ADLTE. In cell-based assays, both variants significantly increased MICAL-1 oxidoreductase activity and induced cell contraction in COS7 cells, which likely resulted from deregulation of F-actin dynamics., Interpretation: MICAL-1 oxidoreductase activity induces disassembly of actin filaments, thereby regulating the organization of the actin cytoskeleton in developing and adult neurons and in other cell types. This suggests that dysregulation of the actin cytoskeleton dynamics is a likely mechanism by which MICAL-1 pathogenic variants lead to ADLTE. Ann Neurol 2018;83:483-493., (© 2018 American Neurological Association.)

Introduction: Young adults generally do not perceive waterpipe tobacco smoking (WTS) to be addictive. Underlying reasons for these false perceptions have received limited research attention and little is known about effective WTS prevention messaging. This study examined perceptions of the addictiveness of WTS among young adults and ascertained their feedback on WTS prevention message content., Methods: Young adult (n=44, Mean [M] age 25.3, SD 2.7, range 18-30) waterpipe tobacco users were recruited online for a cross-sectional survey. Closed-ended measures assessed demographics, waterpipe use, other tobacco consumption, and perceived addictiveness of WTS. Open-ended items assessed perceptions of WTS and ascertained feedback on WTS prevention message content. Quantitative data were analyzed descriptively. Open-ended data were coded to identify emerging themes., Results: Participants reported low perceived addictiveness of WTS (Mean 2.0, SD 0.9, range 1- not at all, 4 - very), perceived chances of becoming addicted (Mean 3.0, SD 1.6, range 1- no chance, 7- certain), and desire to quit (Mean 3.0, SD 1.8, range 1- not at all, 7- very). In open-ended responses, participants indicated social WTS does not lead to addiction and believe it is easy to quit. Some expressed concerns that WTS addiction may lead to health harms, social stigma, and financial costs. Participants indicated messages using vivid imagery and conveying negative health effects could motivate cessation., Conclusions: Young adults view that WTS is not addictive, particularly related to use in social settings. Research can build from this study by developing and testing messages to motivate WTS cessation in young adults., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2017 Mays D.)

The porcine brain closely resembles the human brain in aspects such as development and morphology. Temporal miRNA profiling in the developing embryonic porcine cortex revealed a distinct set of miRNAs, including miR-34c and miR-204, which exhibited a highly specific expression profile across the time of cortical folding. These miRNAs were found to target Doublecortin (DCX), known to be involved in neuron migration during cortical folding of gyrencephalic brains. In vivo modulation of miRNA expression in mouse embryos confirmed that miR-34c and miR-204 can control neuronal migration and cortical morphogenesis, presumably by posttranscriptional regulation of DCX.

The striatum is a large brain nucleus with an important role in the control of movement and emotions. Medium spiny neurons (MSNs) are striatal output neurons forming prominent descending axon tracts that target different brain nuclei. However, how MSN axon tracts in the forebrain develop remains poorly understood. Here, we implicate the Wnt binding receptor Frizzled3 in several uncharacterized aspects of MSN pathway formation [i.e., anterior-posterior guidance of MSN axons in the striatum and their subsequent growth into the globus pallidus (GP), an important (intermediate) target]. In Frizzled3 knock-out mice, MSN axons fail to extend along the anterior-posterior axis of the striatum, and many do not reach the GP. Wnt5a acts as an attractant for MSN axons in vitro, is expressed in a posterior high, anterior low gradient in the striatum, and Wnt5a knock-out mice phenocopy striatal anterior-posterior defects observed in Frizzled3 mutants. This suggests that Wnt5a controls anterior-posterior guidance of MSN axons through Frizzled3. Axons that reach the GP in Frizzled3 knock-out mice fail to enter this structure. Surprisingly, entry of MSN axons into the GP non-cell-autonomously requires Frizzled3, and our data suggest that GP entry may be contingent on the correct positioning of "corridor" guidepost cells for thalamocortical axons by Frizzled3. Together, these data dissect MSN pathway development and reveal (non)cell-autonomous roles for Frizzled3 in MSN axon guidance. Further, they are the first to identify a gene that provides anterior-posterior axon guidance in a large brain nucleus and link Frizzled3 to corridor cell development., Significance Statement: Striatal axon pathways mediate complex physiological functions and are an important therapeutic target, underscoring the need to define how these connections are established. Remarkably, the molecular programs regulating striatal pathway development remain poorly characterized. Here, we determine the embryonic ontogeny of the two main striatal pathways (striatonigral and striatopallidal) and identify novel (non)cell-autonomous roles for the axon guidance receptor Frizzled3 in uncharacterized aspects of striatal pathway formation (i.e., anterior-posterior axon guidance in the striatum and axon entry into the globus pallidus). Further, our results link Frizzled3 to corridor guidepost cell development and suggest that an abnormal distribution of these cells has unexpected, widespread effects on the development of different axon tracts (i.e., striatal and thalamocortical axons)., (Copyright © 2015 the authors 0270-6474/15/3514206-15$15.00/0.)

Integrins have been implicated in various processes of nervous system development, including proliferation, migration, and differentiation of neuronal cells. In this study, we show that the serine/threonine kinase Ndr2 controls integrin-dependent dendritic and axonal growth in mouse hippocampal neurons. We further demonstrate that Ndr2 is able to induce phosphorylation at the activity- and trafficking-relevant site Thr(788/789) of β1-integrin to stimulate the PKC- and CaMKII-dependent activation of β1-integrins, as well as their exocytosis. Accordingly, Ndr2 associates with integrin-positive early and recycling endosomes in primary hippocampal neurons and the surface expression of activated β1-integrins is reduced on dendrites of Ndr2-deficient neurons. The role of Ndr2 in dendritic differentiation is also evident in vivo, because Ndr2-null mutant mice show arbor-specific alterations of dendritic complexity in the hippocampus. This indicates a role of Ndr2 in the fine regulation of dendritic growth; in fact, treatment of primary neurons with Semaphorin 3A rescues Ndr2 knock-down-induced dendritic growth deficits but fails to enhance growth beyond control level. Correspondingly, Ndr2-null mutant mice show a Semaphorin 3A(-/-)-like phenotype of premature dendritic branching in the hippocampus. The results of this study show that Ndr2-mediated integrin trafficking and activation are crucial for neurite growth and guidance signals during neuronal development.

The dynamic re-arrangement of actin filaments is an essential process in the plasticity of synaptic connections during memory formation. In this study, we determined in mice effects of actin filament arrest in the basolateral complex of the amygdala (BLA) at different time points after memory acquisition and re-activation, using the fungal cytotoxin phalloidin. Our data show a selective disruption of auditory cued but not contextual fear memory, when phalloidin was injected 6h after conditioning. In contrast, no effect was observed when phalloidin was applied after 24h, ruling out an interference with the retrieval or expression of conditioned fear. A comparable result was obtained after memory re-activation, hence suggesting similar actin-dependent mechanisms to be active during consolidation and reconsolidation of auditory fear memory. Biochemical analysis showed that phalloidin-mediated filament arrest leads to a transient increase of highly cross-linked actin filaments in the BLA, evident 2h after injection. Together, these observations indicate that dynamic re-arrangements of actin filaments in the BLA during a late phase of fear memory consolidation and reconsolidation are critical for fear memory storage., (Copyright 2010 Elsevier Inc. All rights reserved.)

We report on a patient with a complex heart defect, short webbed neck, multiple other minor features, and a 46,XX,15p+ de novo karyotype. The enlarged short arm of the chromosome 15 was Distamycin-DAPI and C-band negative. Fluorescence in situ hybridization (FISH) using an alpha satellite probe from chromosome 15 demonstrated hybridization only to the normal 15. In situ hybridization using a set of probes that bind to the short arm (17p13) and centromere of chromosome 17 demonstrated that the extra material on chromosome 15, including the centromere, was derived from chromosome 17. Therefore, this patient has a duplication of the centromere and short arm of chromosome 17. Clinical manifestations in this patient were consistent with those in previously described patients with dup (17p).

We describe a 2 1/2-year-old boy who has hirsutism and ringed creases of the extremities associated with an underlying smooth muscle hamartoma. Cutaneous findings in this child resemble those in other reports of the "Michelin tire syndrome." Histologic examination showed numerous well-demarcated fascicles of smooth muscle cells randomly distributed at all levels of the reticular dermis with haphazard orientation. These cells were immunoreactive with desmin, which confirmed their smooth muscle nature. In addition to the skin changes, this child has multiple unusual phenotypic anomalies, some of which have not previously been associated with the Michelin tire syndrome. These include distinctive facial dysmorphia, submucous cleft palate, lateral clefting of the mouth, genital, and dental anomalies. He also developed seizures at age 2 1/2 years and has moderate developmental delay. The patient and his mother have apparently identical paracentric inversions of the long arm of chromosome 7 (46,XY,inv(7)(q22q31.3) with no detectable loss or gain of either chromosomal material or DNA markers from the cystic fibrosis (CFTR) region. The relevance, if any, of the karyotypic abnormality to the phenotype in this child is discussed.

A new case of prenatally detected mosaic trisomy 20 (79% trisomy 20 cells in amniocyte cultures) that was confirmed in newborn tissue is presented. A healthy male infant was delivered at term, with no dysmorphology or apparent malformations; this baby is developing normally. Twenty-five percent of foreskin and 17% of fetal cord cells also showed trisomy 20, while no trisomic cells were detected in newborn blood. High frequency mosaicism for trisomy 20 in this case was thus due to true embryonic origin. Extensive counseling and prenatal follow-up in this case led to an unaffected liveborn, and guarded optimism may be warranted for future cases of mosaic trisomy 20 detected prenatally.

The use of membrane supports as stationary phase, coupled with ligands of choice, allows all kinds of chromatography [Dj. Josić, K. Zeilinger, Y. Lim, M. Raps, W. Hofmann and W. Reutter, J. Chromatogr., 484 (1989) 327] and offers a powerful alternative to both soft gel chromatography and high-performance liquid chromatography. In this work we present affinity membrane chromatography for purification of the enzyme carbonic anhydrase from haemolysates of human erythrocytes. Furthermore, the coupling of the enzymes to the membrane support allows kinetic investigations. As an example, kinetic experiments were carried out by means of carbonic anhydrase coupled to the membrane support using 4-nitrophenyl acetate and 2-chloro-4-nitrophenyl acetate as substrates.

Isoenzymes of carbonic anhydrase were purified by a combination of affinity chromatography and hydrophobic interaction chromatography. Immobilization of sulfonamides on an epoxy-activated support provided a stationary phase for affinity chromatography which was stable to hydrolysis by carbonic anhydrase. A first purification step allowed the isolation of enzymes directly from homogenates of human erythrocytes and rat stomach. Without any further preparation, except the addition of ammonium sulfate to the eluate from affinity chromatography, the isoenzymes could be separated by hydrophobic interaction chromatography with very high recovery of protein and retention of enzymatic activity.

Several steps of purification (octyl-Sepharose chromatography, Blue Sepharose 6B chromatography and sucrose density gradient centrifugation) led to a highly purified aggregate of the enzymes, 3',5'-cyclic-nucleotide phosphodiesterase (PDE) and nucleotidase. The purified enzyme aggregate showed an S value of 7.3 (SE +/- 0.3, n = 10). Further analysis by SDS-polyacrylamide gel electrophoresis (PAGE) revealed two proteins near 67 and 60 kDa. Dissociation of the 7.3 S enzyme aggregate showed a 3.6 S PDE form and a nucleotidase form at 4.2 S. Additionally, higher S value forms of the nucleotidase up to 17 S have been observed. Apparently, they had formed by self-association. SDS-PAGE of the 17 S nucleotidase form showed only one band at 67 kDa. This was taken as evidence for the homogeneity of the 17 S nucleotidase form and the self-association of the nucleotidase after dissociation from the 7.3 S enzyme aggregate. Furthermore, from this it could be concluded that the 67 kDa protein of the 7.3 S enzyme aggregate should be identified with the nucleotidase, and thus the 60 kDa band represents the PDE.