The Growth and Differentiation of Cultured Newborn Rat Keratinocytes

Keratinocytes were cultured from adult and newborn rat epidermis using the 3T3 feeder cell technique. By modifying culture conditions a long-lived line of new- born rat keratinocytes was developed which showed a plating efficiency of 40% and a doubling time of 16 h. The cells produced stratified colonies with tonofilaments, desmosomes, cell envelopes, and keratohyaline granules. When the cells were grown on a collagen gel they formed a thick stratum corneum and many keratohyaline granules. The fibrous proteins synthesized by the newborn rat cultured keratinocytes were different than those of newborn rat epidermis but similar to those of adult rat cultured keratinocytes. A histidine-rich basic protein was identified by immunologic techniques but it appeared to be more heterogeneous than that of newborn rat epidermis. A cell envelope precursor protein was identified by dansyl cadaverine incorporation studies and was identical to a major envelope precursor of newborn rat epidermis. The growth characteristics, colony morphology, and biochemical markers did not change for up to 40 pas- sages and there was no evidence of malignant transformation. Because of their ease of growth and long-term survival these cells are useful for studying a variety of problems related to keratinization

Effect of Minoxidil on Cultured Keratinocytes

Minoxidil has been shown to stimulate hair growth and these studies were undertaken to determine whether the drug had a direct effect on keratinocytes. Cultures of human epidermal cells were treated with minoxidil and it was found that they survived longer than control cultures. In addition, minoxidil prolonged the time that cells could be passed after reaching confluence. The results suggest that minoxidil slows the senescence of keratinocytes, which is similar to what has been found with epidermal growth factor

A Longitudinal Study of Adolescent Identity Development and Harmful Alcohol Use within a Racially/Ethnically Diverse Sample

The development of a clear sense of identity is a key developmental task in adolescence, and recent studies have found that identity synthesis and confusion are associated negatively and positively, respectively, to alcohol use. One alcohol expectancy - tension reduction - coincides with the hypothesis that identity development may prove to be a stressful developmental process, and may thereby serve as a motivator for adolescents to drink when a belief exists that stress can be reduced through alcohol use. In the present study, we examined the mediational effects between identity synthesis and confusion and later alcohol risk via alcohol expectancies and valuations. The sample included 756 adolescents (53% girls; Mage=13.7 years; SD=1.6 years, 41.4% Hispanic, 39.6% non-Hispanic Black, 8.7% non-Hispanic White, 5.2% Asian, and 5.2% Other). Neither identity synthesis nor confusion significantly predicted tension reduction expectancies. Results indicated that tension reduction expectancies at Time 2 positively predicted alcohol risk levels at Time 3 (β=.112, p=.018). Our findings did not fully support our a-priori hypothesis that identity confusion and identity synthesis later predict tension reduction, in turn predicting alcohol risk. Interestingly, however, the findings revealed that identity synthesis did predict declines in expectancy valuations. This research contributes to the current literature and expounds upon the potential interactions between adolescent identity development and alcohol expectancies and specifically, valuations

Relating Teacher Attendance to Student English Language Arts and Math Achievement

On average, teachers in the United States are absent for 9.6 days of student instruction per school year, while in this study\u27s rural Northeast Ohio school district, teachers averaged 16.2 absences in the 2015-16 school year. Teacher absence is a concern because the classroom teacher is often considered the most crucial school-related influence on student achievement. Guided by Bowlby\u27s attachment theory, the purpose of this study was to examine the possible predictive relationships between teacher absences for sick/personal and professional leave as well as other teacher-related variables, including teaching experience, teacher education level, and teacher evaluation results, with the outcome variables of student achievement in 4th through 8th grade English language arts and math. In this quantitative correlational study, data from 36 4th through 8th grade English language arts and math teachers were examined using simple and multiple linear regression models. Results indicated that none of the 5 teacher-related variables were significantly predictive of student achievement. Despite these non-significant results, the district\u27s Board of Education expressed concerns about the public\u27s perception of the district\u27s teacher attendance rate. To address the Board\u27s concern, a 3-day professional development program was created for the Board, administrators, and teachers to collaborate and recommend strategies to increase teacher attendance. The knowledge gained from implementing this project will promote positive social change by offering this and other school districts a variety of options to support the consistent attendance of teachers, which may, in turn, enhance student-teacher relationships, student-teacher engagement, and potentially student achievement over time

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL

Pathogenesis of the cutaneous phenotype in inherited disorders of cholesterol metabolism: Therapeutic implications for topical treatment of these disorders

Molecular geneticists tend to conceptualize disease pathogenesis from the mutated gene outward, an approach that does not take into account the impact of barrier requirements in determining disease phenotype. An ‘outside-to-inside’ perspective has provided quite different explanations for the ichthyoses, including several of the disorders of distal cholesterol metabolism. Elucidation of responsible pathogenic mechanisms also is pointing to appropriate, pathogenesis (pathway)-based therapeutic strategies. In the case of the lipid metabolic disorders, it takes full advantage of new molecular, genetic and cellular pathogenesis information to correct or bypass the metabolic abnormality. This approach fully exploits the unique accessibility of the skin to a topical approach. Moreover, since it will utilize topical lipids and lipid-soluble, and often generic, lipid-soluble drugs, these treatments should be readily transported across the stratum corneum. If successful, this approach could initiate an entirely new departure for the therapy of the ichthyoses. Finally, because these agents are relatively safe and inexpensive, this form of treatment has the potential to be widely-deployed, even in the developing world

Distinct Roles for Neuropilin1 and Neuropilin2 during Mouse Corneal Innervation

Trigeminal sensory innervation of the cornea is critical for protection and synthesis of neuropeptides required for normal vision. Little is known about axon guidance during mammalian corneal innervation. In contrast to the chick where a pericorneal nerve ring forms via Npn/Sema signaling, mouse corneal axons project directly into the presumptive cornea without initial formation of an analogous nerve ring. Here we show that during development of the mouse cornea, Npn1 is strongly expressed by the trigeminal ganglion whereas Npn2 is expressed at low levels. At the same time Sema3A and Sema3F are expressed in distinct patterns in the ocular tissues. Npn1sema−/− mutant corneas become precociously and aberrantly innervated by nerve bundles that project further into the corneal stroma. In contrast, stromal innervation was not affected in Npn2−/− mutants. The corneal epithelium was prematurely innervated in both Npn1sema−/− and Npn2−/− mutants. These defects were exacerbated in Npn1sema−/−;Npn2−/− double mutants, which in addition showed ectopic innervation of the region between the optic cup and lens vesicle. Collectively, our data show that Sema3A/Npn1 and Sema3F/Npn2 signaling play distinct roles and both are required for proper innervation of the mouse cornea