A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.

Centrosomes have critical roles in microtubule organization and in cell signaling.1-8 However, the mechanisms that regulate centrosome function are not fully defined, and thus how defects in centrosomal regulation contribute to disease is incompletely understood. From functional genomic analyses, we find here that PPP2R3C, a PP2A phosphatase subunit, is a distal centriole protein and functional partner of centriolar proteins CEP350 and FOP. We further show that a key function of PPP2R3C is to counteract the kinase activity of MAP3K1. In support of this model, MAP3K1 knockout suppresses growth defects caused by PPP2R3C inactivation, and MAP3K1 and PPP2R3C have opposing effects on basal and microtubule stress-induced JNK signaling. Illustrating the importance of balanced MAP3K1 and PPP2R3C activities, acute overexpression of MAP3K1 severely inhibits centrosome function and triggers rapid centriole disintegration. Additionally, inactivating PPP2R3C mutations and activating MAP3K1 mutations both cause congenital syndromes characterized by gonadal dysgenesis.9-15 As a syndromic PPP2R3C variant is defective in centriolar localization and binding to centriolar protein FOP, we propose that imbalanced activity of this centrosomal kinase-phosphatase pair is the shared cause of these disorders. Thus, our findings reveal a new centrosomal phospho-regulatory module, shed light on disorders of gonadal development, and illustrate the power of systems genetics to identify previously unrecognized gene functions.

Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome.

Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogeneous disorders characterized by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in over 20 genes encoding ciliary proteins have been found to cause OFDS through deleterious structural or functional impacts on primary cilia. We identified by exome sequencing bi-allelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families. Affected individuals presented a novel form of OFDS (OFDS-RAB34) accompanied by cardiac, cerebral, skeletal and anorectal defects. RAB34 encodes a member of the Rab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Unlike many genes required for cilium assembly, RAB34 acts selectively in cell types that use the intracellular ciliogenesis pathway, in which nascent cilia begin to form in the cytoplasm. We find that the protein products of these pathogenic variants, which are clustered near the RAB34 C-terminus, exhibit a strong loss of function. Although some variants retain the ability to be recruited to the mother centriole, cells expressing mutant RAB34 exhibit a significant defect in cilium assembly. While many Rab proteins have been previously linked to ciliogenesis, our studies establish RAB34 as the first small GTPase involved in OFDS and reveal the distinct clinical manifestations caused by impairment of intracellular ciliogenesis.

Cooking, Shopping, and Eating Behaviors of African American and Hispanic Families: Implications for a Culturally Appropriate Meal Kit Intervention.

Families with low incomes face barriers to preparing healthy meals, including decreased food access and limited time, and may turn to fast, low-quality, and inexpensive foods. Affordable and accessible meal kits may reduce these barriers. The objective of this study was to explore the cooking, eating, and shopping behaviors of African American (AA) and Hispanic participants living in the United States with low incomes and determine the knowledge of and preferences for a culturally appropriate meal kit intervention. Trained researchers conducted focus groups using a semi-structured questionnaire with AA and Hispanic food preparers with low incomes. Participant cooking, eating, and shopping behaviors and knowledge of and preferences for a culturally appropriate meal kit intervention were evaluated using thematic analysis. AA participants (n = 16) reported cooking on average 2 to 3 days per week and more often on weekends. Hispanic participants (n = 15) reported cooking 5 days per week and more often during the week. Both groups identified cost as the number one consideration when shopping. Most were unfamiliar with meal kits but indicated they would try an affordable meal kit. AA and Hispanic participants differed in their cooking, eating, and shopping behaviors but were equally interested in trying meal kits if affordable and culturally appropriate.

Acceptability and Willingness to Pay for a Meal Kit Program for African American Families with Low Income: A Pilot Study.

Food insecurity is a persistent issue among individuals with low income and is associated with various nutrition- and health-related consequences. Creative approaches to increasing food access should be investigated as possible solutions. Meal kits, which are boxes or bags of fresh and shelf-stable ingredients for one or more meals, along with a step-by-step recipe showing how to cook each meal at home, may serve as a creative solution. Meal kits have historically been marketed to higher-income demographics. The purpose of this pilot study was to investigate the utilization, acceptability, and willingness to pay for a healthy meal kit program among African American main food preparers with children and low income (n = 36). Participants received a healthy meal kit with three recipes and ingredients, a cooking incentive, and a nutrition handout weekly for six weeks. Data were collected on participants' use, acceptability, and willingness to pay for the meal kits and analyzed using descriptive statistics. The intervention was highly utilized, and participants reported high acceptability ratings for most recipes. After the intervention, participants were willing to pay $88.61 ± 47.47 for a meal kit with three meals, each with four portions, which was higher than indicated at baseline and similar to the cost to produce the kits. Meal kits may offer a creative solution to improving food access if affordable for families with low income.

Sociodemographic patterns of urine sodium excretion and its association with hypertension in Chile: a cross-sectional analysis.

OBJECTIVE: The aim of the study was to determine the main factors (sociodemographic, anthropometric, lifestyle and health status) associated with high Na excretion in a representative population of Chile. DESIGN: Na excretion (g/d), a valid marker of Na intake, was determined by urine analysis and Tanaka's formulas. Blood pressure was measured by trained staff and derived from the mean of three readings recorded after 15 min rest. The associations of Na excretion with blood pressure and the primary correlates of high Na excretion were determined using logistic regression. SETTING: Chileans aged ≥15 years.ParticipantsParticipants (n 2913) from the Chilean National Health Survey 2009-2010. RESULTS: Individuals aged 25 years or over, those who were obese and those who had hypertension, diabetes or metabolic syndrome were more likely to have higher Na excretion. The odds for hypertension increased by 10·2 % per 0·4 g/d increment in Na excretion (OR=1·10; 95 % CI 1·06, 1·14; P < 0·0001). These findings were independent of major confounding factors. CONCLUSIONS: Age, sex, adiposity, sitting behaviours and existing co-morbidities such as diabetes were associated with higher Na excretion levels in the Chilean population. These findings could help policy makers to implement public health strategies tailored towards individuals who are more likely to consume high levels of dietary salt.

Comparative mortality of persons with intellectual disability in California: an update (2000-2010).

This paper updates our 2003 study on the effect of intellectual disability (ID) on mortality in persons with no significant physical disability. As previously, we used the California Department of Developmental Services database to compute mortality rates by age, sex, and severity of ID. There were 64,207 subjects age 5 and older, who contributed 386,000 person-years of follow-up and 1514 deaths during the 2000 to 2010 study period. The excess death rates increased with age, ranging from 0.1 to 6.8 per 1000 in mild/moderate ID, and 3.4 to 6.7 in severe/profound.

Hip and knee joint kinematics during a diagonal jump landing in anterior cruciate ligament reconstructed females.

Anterior cruciate ligament (ACL) injury is a common injury encountered by sport medicine clinicians. Surgical reconstruction is the recommended treatment of choice for those athletes wishing to return to full-contact sports participation and for sports requiring multi-directional movement patterns. The aim of ACL reconstruction is to restore knee joint mechanical stability such that the athlete can return to sporting participation. However, knowledge regarding the extent to which lower limb kinematic profiles are restored following ACL reconstruction is limited. In the present study the hip and knee joint kinematic profiles of 13 ACL reconstructed (ACL-R) and 16 non-injured control subjects were investigated during the performance of a diagonal jump landing task. The ACL-R group exhibited significantly less peak knee joint flexion (P=0.01). Significant between group differences were noted for time averaged hip joint sagittal plane (P<0.05) and transverse plane (P<0.05) kinematic profiles, as well as knee joint frontal plane (P<0.05) and sagittal plane (P<0.05) kinematic profiles. These results suggest that aberrant hip and knee joint kinematic profiles are present following ACL reconstruction, which could influence future injury risk.

Lower limb kinematic alterations during drop vertical jumps in female athletes who have undergone anterior cruciate ligament reconstruction.

The aim of this study was to determine if anterior cruciate ligament reconstructed (ACL-R) female athletes exhibit altered lower limb kinematic profiles during jump landing when compared to a non-injured age, sex, and activity matched control group. Fourteen ACL-R and 14 non-injured control subjects performed 3 vertical drop jump (DVJ) trials. Lower limb kinematics were recorded at 200 Hz. Peak and time-averaged angular displacements were quantified and utilized for between-group analysis. The ACL-R group displayed altered hip joint frontal and transverse plane kinematic alterations, and knee joint frontal and sagittal plane kinematic alterations. Specifically the ACL-R group displayed an increased adducted (p < 0.05) and internally rotated (p < 0.05) hip joint position, both peak and time-averaged, following landing. The ACL-R group also displayed a decreased adducted (p < 0.05) and flexed (p < 0.05) position of the knee joint following landing. The observed aberrant lower limb kinematics could pre-dispose ACL-R athletes to potential future knee joint injuries. Further studies are required to determine in a prospective manner whether such deficits increase the incidence of recurrent ACL injury, and whether specific sensorimotor protocols following ACL reconstruction can minimize these kinematic deficits.

An introductory biology lab that uses enzyme histochemistry to teach students about skeletal muscle fiber types.

One important goal of introductory biology laboratory experiences is to engage students directly in all steps in the process of scientific discovery. Even when laboratory experiences are built on principles discussed in the classroom, students often do not adequately apply this background to interpretation of results they obtain in lab. This disconnect has been described at the level of medical education (4), so it should not be surprising that educators have struggled with this same phenomenon at the undergraduate level. We describe a new introductory biology lab that challenges students to make these connections. The lab utilizes enzyme histochemistry and morphological observations to draw conclusions about the composition of functionally different types of muscle fibers present in skeletal muscle. We report that students were not only successful at making these observations on a specific skeletal muscle, the gastrocnemius of the frog Rana pipiens, but that they were able to connect their results to the principles of fiber type differences that exist in skeletal muscles in all vertebrates.