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H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that in male meiosis, ATF7IP2 amasses on autosomal and X-pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X-pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein's essential roles in the maintenance of MSCI, suppression of retrotransposons, and global up-regulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.

BACKGROUND: Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated. METHODS: Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR). RESULTS: Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002). CONCLUSIONS: High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival. IMPACT: Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.

Depression, anxiety, and stress are common mental health problems among adolescents. Cross-sectional and longitudinal studies have found that students who suffer from mental health problems (e.g., ADHD, anxiety, or depression) tend to manifest school and social problems. It is urgent to identify and intervene early to help children with mental health problems to improve their life outcomes. Unfortunately, research has shown that a significant proportion of children who suffer from behavioral or emotional problems remain unidentified because their symptoms are too mild to be noticed through casual observation by caregivers and teachers. As a result, their symptoms continue to develop gradually and eventually become mental illnesses. When mild to moderate symptoms become a noticeable mental illness, treatment becomes long-term, more invasive, and expensive. Early detection of children who are at risk of behavioral or emotional problems is possible through universal mental health screening in the school setting. The present study focused on the Behavioral and Emotional Screening System (BESS; Kamphaus & Reynolds, 2007) to identify students who were at mild risk of mental health problems and to examine their academic trajectories over four years. The findings suggest that students at mild risk of behavioral and emotional problems showed similar academic performance as other students. As a result, students with mild to moderate symptoms can be easily overlooked if academic performance were relied on as an indicator of mental health risk. The current results lend support for conducting universal behavioral and emotional risk screening at schools. A brief screener, applied universally, appears to be an effective solution for identifying students at mild risk of behavioral and emotional problems and acting early to prevent these problems from worsening.

Teacher quality has been found to offset the adverse effect of racial and socioeconomic differences in academic achievement; and teacher quality is often thought to be the product of a quality education. However, existing literature has produced mixed results regarding the relationship between student achievement and teachers' possession of advanced degrees (ADs). Despite these mixed results, ADs are often the most efficient (if not the only) way for teachers to earn certification and salary upgrades. A longitudinal, multiphase mixed-methods explanatory study aimed to bridge shortcomings of existing research on the effects of teachers obtaining ADs. Associations between teacher credentials and middle grades students' academic growth were examined by differentiating teachers' degree level (bachelor's, master's, specialist's) and field (content-related, non-content-related). Teachers and school leaders were also interviewed in order to broaden our understandings of the impact ADs make in areas besides student achievement. Findings suggest that inconsistency in associations between teacher ADs and student achievement may be attributable to variation in a number of individual, programmatic, and institutional factors.

This study examined the implementation of high-stakes adoption of edTPA® in one state in the year prior to consequential use of edTPA scores for teacher licensure. Using a mixed methods design, we investigated concerns of coordinators who were responsible for edTPA implementation in their institutions. We utilized the Concerns Based Adoption Model (CBAM) to understand edTPA coordinators' "Stages of Concern," the nature of the challenges they faced, and the professional development opportunities that alleviated their concerns. Based on the CBAM survey, the most common "Stage of Concern" for edTPA coordinators was "Management." Coordinators' interviews revealed the nature of their concerns at different stages and how the size of their institution and supportive resources at particular times may have played a crucial role in shaping the edTPA roll-out in their institutions. The use of the CBAM framework enabled edTPA coordinators (a) to understand their own concerns about the high-stakes policy, (b) to articulate the complexities involved in implementing edTPA initiatives, and (c) to underscore the importance of relating concerns to appropriate professional development opportunities and support for themselves as well as their faculty.

During reading instruction, sustaining learners' reading motivation (RM) may be a challenge but a requisite when the goal is to keep learners reading. In the context of the present study, it was examined as to how RM may be sustained in a reading course. For this purpose, information on learners' RM was collected in a semester-long university reading course with 118 Korean learners of English at the pre- and post-instructional stages of reading. RM was assessed with "Motivations for Reading Questionnaire" before and after reading instruction. Results indicated that "reading involvement" had decreased for all learners whereas the less skilled learners demonstrated an increase of "reading efficacy" and a drop in "reading for grades." A linear multiple regression further indicated that "reading efficacy" was a significant predictor of reading proficiency only for the skilled learners. Implications are presented on how reading needs to be conducted by allowing learners to choose their own materials, which in turn may have an effect on developing more robust forms of RM.

NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2-/- mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2-/- Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2-/- Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2-/- mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition.

Recently developed methods for transforming 2D patterns of thin-film materials into 3D mesostructures create many interesting opportunities in microsystems design. A growing area of interest is in multifunctional thermal, electrical, chemical, and optical interfaces to biological tissues, particularly 3D multicellular, millimeter-scale constructs, such as spheroids, assembloids, and organoids. Herein, examples of 3D mechanical interfaces are presented, in which thin ribbons of parylene-C form the basis of transparent, highly compliant frameworks that can be reversibly opened and closed to capture, envelop, and mechanically restrain fragile 3D tissues in a gentle, nondestructive manner, for precise measurements of viscoelastic properties using techniques in nanoindentation. Finite element analysis serves as a design tool to guide selection of geometries and material parameters for shape-matching 3D architectures tailored to organoids of interest. These computational approaches also quantitate all aspects of deformations during the processes of opening and closing the structures and of forces imparted by them onto the surfaces of enclosed soft tissues. Studies of cerebral organoids by nanoindentation show effective Youngs moduli in the range from 1.5 to 2.5 kPa depending on the age of the organoid. This collection of results suggests broad utility of compliant 3D mesostructures in noninvasive mechanical measurements of millimeter-scale, soft biological tissues.

Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.

Use of edTPA for preservice teacher assessment is becoming increasingly common across the country, with some states, including Georgia, mandating the passing of the edTPA for initial teacher licensure. This state-wide study investigated whether edTPA as a new policy initiative was being integrated by the teacher education programs and faculty in their practice. The edTPA Levels of Integration (LoI) Survey was sent to faculty, eliciting 145 responses. Results showed that the integration of edTPA was significantly higher at the program level than in faculty's personal practice and that, most aspects of edTPA were currently being used at the mechanical level. The five-factor solution from the exploratory factor analysis and a high Cronbach's alpha showed that this survey is internally consistent and a valid measure for measuring edTPA faculty's LoI. These factors were robust and strong constructs for understanding faculty's use of edTPA both at the program level and the individual faculty level.

BACKGROUND: Autism spectrum disorder involves neurodevelopmental dysregulations that lead to visible symptoms at early stages of life. Many autism spectrum disorder-related mechanisms suggested by animal studies are supported by demonstrated improvement in autistic-like phenotypes in adult animals following experimental reversal of dysregulated mechanisms. However, whether such mechanisms also act at earlier stages to cause autistic-like phenotypes is unclear. METHODS: We used Shank2-/- mice carrying a mutation identified in human autism spectrum disorder (exons 6 and 7 deletion) and combined electrophysiological and behavioral analyses to see whether early pathophysiology at pup stages is different from late pathophysiology at juvenile and adult stages and whether correcting early pathophysiology can normalize late pathophysiology and abnormal behaviors in juvenile and adult mice. RESULTS: Early correction of a dysregulated mechanism in young mice prevents manifestation of autistic-like social behaviors in adult mice. Shank2-/- mice, known to display N-methyl-D-aspartate receptor (NMDAR) hypofunction and autistic-like behaviors at postweaning stages after postnatal day 21 (P21), show the opposite synaptic phenotype-NMDAR hyperfunction-at an earlier preweaning stage (∼P14). Moreover, this NMDAR hyperfunction at P14 rapidly shifts to NMDAR hypofunction after weaning (∼P24). Chronic suppression of the early NMDAR hyperfunction by the NMDAR antagonist memantine (P7-P21) prevents NMDAR hypofunction and autistic-like social behaviors from manifesting at later stages (∼P28 and P56). CONCLUSIONS: Early NMDAR hyperfunction leads to late NMDAR hypofunction and autistic-like social behaviors in Shank2-/- mice, and early correction of NMDAR dysfunction has the long-lasting effect of preventing autistic-like social behaviors from developing at later stages.

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value