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Structurally coloured materials that change their colour in response to mechanical stimuli are uniquely suited for optical sensing and visual communication 1-4 . The main barrier to their widespread adoption is a lack of manufacturing techniques that offer spatial control of the materials' nanoscale structures across macroscale areas. Here, by adapting Lippmann photography 5 , we report an approach for producing large-area, structurally coloured sheets with a rich and easily controlled design space of colour patterns, spectral properties, angular scattering characteristics and responses to mechanical stimuli. Relying on just a digital projector and commercially available photosensitive elastomers, our approach is fast, scalable, affordable and relevant for a wide range of manufacturing settings. We also demonstrate prototypes for mechanosensitive healthcare materials and colorimetric strain and stress sensing for human-computer interaction and robotics., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: With the capacity to modulate gene networks in an environmentally-sensitive manner, the role of epigenetic systems in mental disorders has come under intense investigation. Dysregulation of epigenetic effectors, including microRNAs and histone-modifying enzymes, may better explain the role of environmental risk factors and the observed heritability rate that cannot be fully attributed to known genetic risk alleles. Here, we aimed to identify novel epigenetic targets of the schizophrenia-associated microRNA 132 (miR-132)., Methods: Histone modifications were quantified by immunodetection in response to viral-mediated overexpression of miR-132 while a luminescent reporter system was used to validate targets of miR-132 in vitro. Genome-wide profiling, quantitative PCR and NanoSting were used to quantify gene expression in post-mortem human brains, neuronal cultures and prefrontal cortex (PFC) of mice chronically exposed to antipsychotics. Following viral-mediated depletion of Enhancer of Zeste 1 (EZH1) in the murine PFC, behaviors including sociability and motivation were assessed using a 3-chambered apparatus and forced-swim test, respectively., Results: Overexpression of miR-132 decreased global histone 3 lysine 27 tri-methylation (H3K27me3), a repressive epigenetic mark. Moreover, the polycomb-associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated in the PFC of schizophrenics. Unlike its homolog EZH2, expression of EZH1 in the murine PFC decreased following chronic exposure to antipsychotics. Viral-mediated depletion of EZH1 in the mouse PFC attenuated sociability, enhanced motivational behaviors, and affected gene expression pathways related to neurotransmission and behavioral phenotypes., Conclusions: EZH1 is dysregulated in schizophrenia, sensitive to antipsychotic medications, and a brain-enriched miR-132 target that controls neurobehavioral phenotypes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have been implicated in a number of complex diseases. Schizophrenia and other major psychiatric and neurodevelopmental disorders are associated with abnormalities in multiple epigenetic mechanisms, resulting in altered gene expression during development and adulthood. Polymorphisms and copy number variants in schizophrenia risk genes contribute to the high heritability of the disease, but environmental factors that lead to epigenetic modifications may either reduce or exacerbate the expression of molecular and behavioral phenotypes associated with schizophrenia and related disorders. In the present paper, we will review the current understanding of molecular dysregulation in schizophrenia, including disruption of the dopamine, NMDA, and GABA signaling pathways, and discuss the role of epigenetic factors underlying disease pathology., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A study was conducted at Texas A&M University Baylor College of Dentistry (TAMBCD) in fall 2011 to identify the reasons underrepresented minority (URM) students chose to attend TAMBCD, the factors that supported their success as enrolled students, and their perceptions of the institution's cultural climate. A survey distributed online to all URM students received a 79 percent response rate (129/164). The respondents were primarily Hispanic (62 percent Mexican American and other Hispanic) and African American (33 percent) and had attended a college pipeline program (53 percent). The top reasons these students chose TAMBCD were reputation, location, and automatic acceptance or familiarity from being in a predental program. Alumni had most influenced them to attend. Regarding support services, the largest percentage reported not using any (44 percent); personal advising and tutoring were reported to be the most commonly used. In terms of climate, discrimination was reported by 22 percent (n=29), mostly from classmates and clinical faculty. The majority (87 percent) reported their cultural competence program was "effective" and agreed that faculty (83 percent), staff (85 percent), and students (75 percent) were culturally competent. Overall, the students were "satisfied" with how they were treated (88 percent), their education (91 percent), and the services/resources (92 percent). This information is being used to continue to improve the school's cultural climate and to conduct a broader assessment of all students.

Over the past two decades, it has become clear just how much of our physiology is under the control of the suprachiasmatic nucleus (SCN) and the cell-intrinsic molecular clock that ticks with a periodicity of approximately 24 h. The SCN prepares our digestive system for meals, our adrenal axis for the stress of waking up in the morning, and the genes expressed in our muscles when we prepare to exercise. Long before molecular studies of genes such as Clock, Bmal1, and the Per homologs were possible, it was obvious that female reproductive function was under strict circadian control at every level of the hypothalamic-pituitary-gonadal axis, and in the establishment and successful maintenance of pregnancy. This review highlights our current understanding of the role that the SCN plays in regulating female reproductive physiology, with a special emphasis on the advances made possible through the use of circadian mutant mice.

Ipomoea purpurea (common morning glory) is an annual vine native to Mexico that is well known for its large, showy flowers. Humans have spread morning glories worldwide, owing to the horticultural appeal of morning glory flowers. Ipomoea purpurea is an opportunistic colonizer of disturbed habitats including roadside and agricultural settings, and it is now regarded as a noxious weed in the Southeastern US. Naturalized populations in the Southeastern United States are highly polymorphic for a number of flower color morphs, unlike native Mexican populations that are typically monomorphic for the purple color morph. Although I. purpurea was introduced into the United States from Mexico, little is known about the specific geographic origins of US populations relative to the Mexican source. We use resequencing data from 11 loci and 30 I. purpurea accessions collected from the native range of the species in Central and Southern Mexico and 8 accessions from the Southeastern United States to infer likely geographic origins in Mexico. Based on genetic assignment analysis, haplotype composition, and the degree of shared polymorphism, I. purpurea samples from the Southeastern United States are genetically most similar to samples from the Valley of Mexico and Veracruz State. This supports earlier speculation that I. purpurea in the Southeastern United States was likely to have been introduced by European colonists from sources in Central Mexico.

Policies exist to promote fairness and equal access to opportunities and services that address basic human needs of all U.S. citizens. Nonetheless, health disparities continue to persist among certain subpopulations, including those of racial, ethnic, geographic, socioeconomic, and other cultural identity groups. The Commission on Dental Accreditation (CODA) has added standards to address this concern. According to the most recent standards, adopted in 2010 for implementation in July 2013, CODA stipulates that "students should learn about factors and practices associated with disparities in health." Thus, it is imperative that dental schools develop strategies to comply with this addition. One key strategy for compliance is the inclusion of cultural competence training in the dental curriculum. A survey, the Dental Tool for Assessing Cultural Competence Training (D-TACCT), based on the Association of American Medical Colleges' Tool for Assessing Cultural Competence Training (TACCT), was sent to the academic deans at seventy-one U.S. and Canadian dental schools to determine best practices for cultural competence training. The survey was completed by thirty-seven individuals, for a 52 percent response rate. This article describes the use of this survey as a guide for developing culturally competent strategies and enhancing cultural competence training in dental schools.

Mutations that cause intellectual disability (ID) and autism spectrum disorder (ASD) are commonly found in genes that encode for synaptic proteins. However, it remains unclear how mutations that disrupt synapse function impact intellectual ability. In the SYNGAP1 mouse model of ID/ASD, we found that dendritic spine synapses develop prematurely during the early postnatal period. Premature spine maturation dramatically enhanced excitability in the developing hippocampus, which corresponded with the emergence of behavioral abnormalities. Inducing SYNGAP1 mutations after critical developmental windows closed had minimal impact on spine synapse function, whereas repairing these pathogenic mutations in adulthood did not improve behavior and cognition. These data demonstrate that SynGAP protein acts as a critical developmental repressor of neural excitability that promotes the development of life-long cognitive abilities. We propose that the pace of dendritic spine synapse maturation in early life is a critical determinant of normal intellectual development., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Rationale: Identification of biomarkers that establish diagnosis or treatment response is critical to the advancement of research and management of patients with depression., Objective: Our goal was to identify biomarkers that can potentially assess fluoxetine response and risk to poor treatment outcome., Methods: We measured behavior, gene expression, and the levels of 36 neurobiochemical analytes across a panel of genetically diverse mouse inbred lines after chronic treatment with water or fluoxetine., Results: Glyoxylase 1 (GLO1) and guanine nucleotide-binding protein 1 (GNB1) mostly account for baseline anxiety-like and depressive-like behavior, indicating a common biological link between depression and anxiety. Fluoxetine-induced biochemical alterations discriminated positive responders, while baseline neurobiochemical differences differentiated negative responders (p < 0.006). Results show that glial fibrillary acidic protein, S100 beta protein, GLO1, and histone deacetylase 5 contributed most to fluoxetine response. These proteins are linked within a cellular growth/proliferation pathway, suggesting the involvement of cellular genesis in fluoxetine response. Furthermore, a candidate genetic locus that associates with baseline depressive-like behavior contains a gene that encodes for cellular proliferation/adhesion molecule (Cadm1), supporting a genetic basis for the role of neuro/gliogenesis in depression., Conclusion: We provided a comprehensive analysis of behavioral, neurobiochemical, and transcriptome data across 30 mouse inbred strains that has not been accomplished before. We identified biomarkers that influence fluoxetine response, which, altogether, implicate the importance of cellular genesis in fluoxetine treatment. More broadly, this approach can be used to assess a wide range of drug response phenotypes that are challenging to address in human samples.

Schizophrenia is characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of 854 miRNAs in prefrontal cortical tissue from 100 control, schizophrenic, and bipolar subjects. The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects. Consistent with NMDA-mediated hypofunction observed in schizophrenic subjects, administration of an NMDA antagonist to adult mice results in miR-132 down-regulation in the prefrontal cortex. Furthermore, miR-132 expression in the murine prefrontal cortex exhibits significant developmental regulation and overlaps with critical neurodevelopmental processes during adolescence. Adult prefrontal expression of miR-132 can be down-regulated by pharmacologic inhibition of NMDA receptor signaling during a brief postnatal period. Several key genes, including DNMT3A, GATA2, and DPYSL3, are regulated by miR-132 and exhibited altered expression either during normal neurodevelopment or in tissue from adult schizophrenic subjects. Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia.

There is a large disparity between the proportions of African-Americans, Hispanics, and Native Americans in the general population and in the dental profession. While these underrepresented minorities (URMs) as a group make up almost 30% of the United States population, they constitute only about 6% of the nation's dentists. Eliminating this disparity is important in addressing access to care for underrepresented groups. Texas A&M Health Science Center Baylor College of Dentistry (TAMHSC-BCD) enrolled greater numbers and proportions of URM students than any other non-minority school from 2006-2010. Strategies used to achieve this level of diversity include a Whole File Review process; career awareness activities for elementary, junior high and high school students; and academic enrichment programs for college students and college graduates. Retaining and graduating URM students is just as important as enrolling them. TAMHSC-BCD's retention rate over the last five years is 95.7% for all students and 92.5% for URM students. A wide range of services aids in the retention process. These services are available to all students and include monitoring of students' academic performance followed up with academic advisement as appropriate, peer tutoring, an alternative five-year curriculum, professional psychological counseling, professional learning assessments, social support; and mentoring through student organizations. The retention program at TAMHSC-BCD can serve as a model for other dental and other health professions schools seeking ways to ensure the academic success of their URM students. The more of these students we enroll and graduate, the more the problem of access to dental care is addressed.

There is no better way to give back to dentistry--which has given us so much as dentists--than to mentor a young person into the profession. With the size of the applicant pool dramatically increasing over the past 10 years (73.6 percent), the challenge of the admissions process has increased as well. To put it simply, the "line" of those desiring dentistry as a profession has become quite long. In 2010, based upon data from the Texas Medical and Dental Schools Application Service, the ratio of dental applicants to positions exceeded the ratio of applicants to medical school positions! We haven't seen ratios like this since the late 1970's. This guide will aid mentoring dentists in the process of helping their mentees to be successful as applicants, dental students and, ultimately, dental practitioners.

Background: Animal models of human behavioral endophenotypes, such as the Tail Suspension Test (TST) and the Open Field assay (OF), have proven to be essential tools in revealing the genetics and mechanisms of psychiatric diseases. As in the human disorders they model, the measurements generated in these behavioral assays are significantly impacted by the genetic background of the animals tested. In order to better understand the strain-dependent phenotypic variability endemic to this type of work, and better inform future studies that rely on the data generated by these models, we phenotyped 33 inbred mouse strains for immobility in the TST, a mouse model of behavioral despair, and for activity in the OF, a model of general anxiety and locomotor activity., Results: We identified significant strain-dependent differences in TST immobility, and in thigmotaxis and distance traveled in the OF. These results were replicable over multiple testing sessions and exhibited high heritability. We exploited the heritability of these behavioral traits by using in silico haplotype-based association mapping to identify candidate genes for regulating TST behavior. Two significant loci (-logp >7.0, gFWER adjusted p value <0.05) of approximately 300 kb each on MMU9 and MMU10 were identified. The MMU10 locus is syntenic to a major human depressive disorder QTL on human chromosome 12 and contains several genes that are expressed in brain regions associated with behavioral despair., Conclusions: We report the results of phenotyping a large panel of inbred mouse strains for depression and anxiety-associated behaviors. These results show significant, heritable strain-specific differences in behavior, and should prove to be a valuable resource for the behavioral and genetics communities. Additionally, we used haplotype mapping to identify several loci that may contain genes that regulate behavioral despair.

The study of expression quantitative trait loci (eQTL) is a powerful way of detecting transcriptional regulators at a genomic scale and for elucidating how natural genetic variation impacts gene expression. Power and genetic resolution are heavily affected by the study population: whereas recombinant inbred (RI) strains yield greater statistical power with low genetic resolution, using diverse inbred or outbred strains improves genetic resolution at the cost of lower power. In order to overcome the limitations of both individual approaches, we combine data from RI strains with genetically more diverse strains and analyze hippocampus eQTL data obtained from mouse RI strains (BXD) and from a panel of diverse inbred strains (Mouse Diversity Panel, MDP). We perform a systematic analysis of the consistency of eQTL independently obtained from these two populations and demonstrate that a significant fraction of eQTL can be replicated. Based on existing knowledge from pathway databases we assess different approaches for using the high-resolution MDP data for fine mapping BXD eQTL. Finally, we apply this framework to an eQTL hotspot on chromosome 1 (Qrr1), which has been implicated in a range of neurological traits. Here we present the first systematic examination of the consistency between eQTL obtained independently from the BXD and MDP populations. Our analysis of fine-mapping approaches is based on 'real life' data as opposed to simulated data and it allows us to propose a strategy for using MDP data to fine map BXD eQTL. Application of this framework to Qrr1 reveals that this eQTL hotspot is not caused by just one (or few) 'master regulators', but actually by a set of polymorphic genes specific to the central nervous system.

MicroRNAs (miRNAs) are small regulatory RNAs that individually regulate up to several hundred genes, and collectively may regulate as much as two-thirds of the transcriptome. Recent evidence supports a role for miRNA dysregulation in psychiatric and neurological disorders, including schizophrenia, bipolar disorder, and autism. Small changes in miRNA expression can fine-tune the expression of multiple genes within a biological network, suggesting that miRNA dysregulation may underlie many of the molecular changes observed in psychiatric disease, and that therapeutic regulation of miRNA levels may represent a novel treatment option., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

The Tail Suspension Test (TST), which measures behavioral despair, is widely used as an animal model of human depressive disorders and antidepressant efficacy. In order to identify novel genes involved in the regulation of TST performance, we crossed an inbred strain exhibiting low immobility in the TST (RIIIS/J) with two high-immobility strains (C57BL/6J and NZB/BlNJ) to create two distinct F2 hybrid populations. All F2 offspring (n = 655) were genotyped at high density with a panel of SNP markers. Whole-genome interval mapping of the F2 populations identified statistically significant quantitative trait loci (QTLs) on mouse chromosomes (MMU) 4, 6, and X. Microarray analysis of hippocampal gene expression in the three parental strains was used to identify potential candidate genes within the MMUX QTLs identified in the NZB/BlNJ x RIIIS/J cross. Expression of Gabra3, which encodes the GABA(A) receptor alpha3 subunit, was robust in the hippocampus of B6 and RIIIS mice but absent from NZB hippocampal tissue. To verify the role of Gabra3 in regulating TST behavior in vivo, mice were treated with SB-205384, a positive modulator of the alpha3 subunit. SB-205384 significantly reduced TST immobility in B6 mice without affecting general activity, but it had no effect on behavior in NZB mice. This work suggests that GABRA3 regulates a behavioral endophenotype of depression and establishes this gene as a viable new target for the study and treatment of human depression.

Purpose: A common problem associated with implant-supported prostheses is the fracture of denture teeth. This study was designed to compare the fracture modes of three denture teeth by compressive load at a 30 degrees off-axis angle., Material and Methods: Three denture teeth (Vident Duostat, Ivoclar Vivadent, and Dentsply Trubyte) processed to two denture base processing systems [injection-molded (IM) SR-Ivocap system and compression-molded (CM) denture base resin] were evaluated. Each specimen was processed to a metal framework. Ultimate failure strength of each system when point loaded at a 30 degrees off-axis angle was recorded, along with a visual inspection of each specimen., Results: The average load fracture for each group was (in N): Vident CM 1106.97 +/- 223.20, Vident IM 1168.18 +/- 322.52, Dentsply CM 1098.08 +/- 286.32, Dentsply IM 1023.80 +/- 282.45, Ivoclar CM 1616.98 +/- 204.87, and Ivoclar IM 1373.54 +/- 282.58. There was a significant difference between the groups and the Ivoclar CM group. The Ivoclar CM group had the highest average load force, and the Dentsply IM group had the lowest average load force. On average, the teeth within the groups fractured at a higher compression force than the average maximum occlusal force in natural dentition. Dentsply and Vident denture teeth fractured more horizontally, and the Ivoclar denture teeth fractured more vertically within the groups. There was no significant difference among the groups between the IM and CM processing methods., Conclusions: In the present in vitro study, all specimens were able to withstand 30 degrees off-axis loading with the exception of one specimen. With these results, this would indicate that these denture teeth are able to withstand normal occlusal forces.

Despite widespread use of antidepressants, the factors underlying the behavioral response to antidepressants are unknown. It has been shown that antidepressant treatment promotes the proliferation and survival of neurons in the adult hippocampus via enhanced serotonergic signaling, but it is unclear whether hippocampal neurogenesis is responsible for the behavioral response to antidepressants. Furthermore, a large subpopulation of patients fails to respond to antidepressant treatment due to presumed underlying genetic factors. In the present study, we have used the phenotypic and genotypic variability of inbred mouse strains to show that there is a genetic component to both the behavioral and neuronal effects of chronic fluoxetine treatment, and that this antidepressant induces an increase in hippocampal cell proliferation only in the strains that also show a positive behavioral response to treatment. Furthermore, the behavioral and neuronal responses are associated with an upregulation of genes known to promote neuronal proliferation and survival. These results suggest that inherent genetic predisposition to increased serotonin-induced neurogenesis may be a determinant of antidepressant efficacy.

Circadian rhythms are approximate 24-h behavioral and physiological cycles that function to prepare an organism for daily environmental changes. The basic clock mechanism is a network of transcriptional-translational feedback loops that drive rhythmic expression of genes over a 24-h period. The objectives of this study were to identify transcripts with a circadian pattern of expression in adult skeletal muscle and to determine the effect of the Clock mutation on gene expression. Expression profiling on muscle samples collected every 4 h for 48 h was performed. Using COSOPT, we identified a total of 215 transcripts as having a circadian pattern of expression. Real-time PCR results verified the circadian expression of the core clock genes, Bmal1, Per2, and Cry2. Annotation revealed cycling genes were involved in a range of biological processes including transcription, lipid metabolism, protein degradation, ion transport, and vesicular trafficking. The tissue specificity of the skeletal muscle circadian transcriptome was highlighted by the presence of known muscle-specific genes such as Myod1, Ucp3, Atrogin1 (Fbxo32), and Myh1 (myosin heavy chain IIX). Expression profiling was also performed on muscle from the Clock mutant mouse and sarcomeric genes such as actin and titin, and many mitochondrial genes were significantly downregulated in the muscle of Clock mutant mice. Defining the circadian transcriptome in adult skeletal muscle and identifying the significant alterations in gene expression that occur in muscle of the Clock mutant mouse provide the basis for understanding the role of circadian rhythms in the daily maintenance of skeletal muscle.

Circadian rhythms of cell and organismal physiology are controlled by an autoregulatory transcription-translation feedback loop that regulates the expression of rhythmic genes in a tissue-specific manner. Recent studies have suggested that components of the circadian pacemaker, such as the Clock and Per2 gene products, regulate a wide variety of processes, including obesity, sensitization to cocaine, cancer susceptibility, and morbidity to chemotherapeutic agents. To identify a more complete cohort of genes that are transcriptionally regulated by CLOCK and/or circadian rhythms, we used a DNA array interrogating the mouse protein-encoding transcriptome to measure gene expression in liver and skeletal muscle from WT and Clock mutant mice. In WT tissue, we found that a large percentage of expressed genes were transcription factors that were rhythmic in either muscle or liver, but not in both, suggesting that tissue-specific output of the pacemaker is regulated in part by a transcriptional cascade. In comparing tissues from WT and Clock mutant mice, we found that the Clock mutation affects the expression of many genes that are rhythmic in WT tissue, but also profoundly affects many nonrhythmic genes. In both liver and skeletal muscle, a significant number of CLOCK-regulated genes were associated with the cell cycle and cell proliferation. To determine whether the observed patterns in cell-cycle gene expression in Clock mutants resulted in functional dysregulation, we compared proliferation rates of fibroblasts derived from WT or Clock mutant embryos and found that the Clock mutation significantly inhibits cell growth and proliferation.

In the female mouse, ovulation and estrous cyclicity are under both hormonal and circadian control. We have shown that mice with a mutation in the core circadian gene Clock have abnormal estrous cycles and do not have a luteinizing hormone (LH) surge on the afternoon of proestrus due to a defect at the hypothalamic level. In the present study, we tested the hypotheses that vasopressin (AVP) can act as a circadian signal to regulate the proestrous release of LH, and that this signal is deficient in the Clock mutant. We found that Avp expression in the suprachiasmatic nucleus (SCN) and AVP 1a receptor (Avpr1a) expression in the hypothalamus is reduced in Clock mutant mice compared to wild-type mice. Intracerebroventricular (i.c.v.) injection of AVP on the afternoon of proestrus is sufficient to induce LH secretion, which reaches surge levels in 50% of Clock mutant mice. The effect of AVP on the Clock mutant LH surge is mediated by AVPR1A, as co-infusion of AVP and an AVPR1A-specific antagonist prevents AVP induction of LH release, although infusion of an AVPR1A antagonist into wild-type mice failed to prevent a proestrous LH surge. These results suggest that reduced hypothalamic AVP signaling plays a role in the absence of the proestrous LH surge in Clock mutant mice. The results also support the hypothesis that AVP produced by the SCN may be a circadian signal that regulates LH release.

Objective: To test the effects of curing time and light intensity on the shear bond strength of adhesive composites for stainless-steel orthodontic brackets., Materials and Methods: An argon laser at four different power settings (100, 150, 200, and 250 mW) and four different exposure times (5, 10, 15, and 20 seconds) was used to bond adhesive-precoated (APC) stainless-steel incisor brackets to the facial surfaces of 154 bovine incisors. The shear bond strength of each specimen in 16 randomly divided groups was randomly tested to failure using an Instron universal testing machine. Each mode of failure was described using the adhesive remnant index (ARI)., Results: The ARI scoring system showed that the location of bond failure did not differ significantly in relation to exposure time (P = .40). However, the location of bond failure was significantly different in relation to light power (P = .03)., Conclusions: A short exposure time and a low power setting produce shear bond strengths equivalent to those produced by longer exposure times and higher power settings.

Spontaneous action potentials in the suprachiasmatic nucleus (SCN) are necessary for normal circadian timing of behavior in mammals. The SCN exhibits a daily oscillation in spontaneous firing rate (SFR), but the ionic conductances controlling SFR and the relationship of SFR to subsequent circadian behavioral rhythms are not understood. We show that daily expression of the large conductance Ca(2+)-activated K(+) channel (BK) in the SCN is controlled by the intrinsic circadian clock. BK channel-null mice (Kcnma1(-/-)) have increased SFRs in SCN neurons selectively at night and weak circadian amplitudes in multiple behaviors timed by the SCN. Kcnma1(-/-) mice show normal expression of clock genes such as Arntl (Bmal1), indicating a role for BK channels in SCN pacemaker output, rather than in intrinsic time-keeping. Our findings implicate BK channels as important regulators of the SFR and suggest that the SCN pacemaker governs the expression of circadian behavioral rhythms through SFR modulation.

Objective: The aims of this study were to evaluate increasing exposure times and distance between source (light-emitting diode) and adhesive composite on the shear bond strength (SBS) of stainless steel brackets., Materials and Methods: Stainless steel maxillary incisor brackets (3M Unitek, Monrovia, Calif) were bonded to the facial surfaces of 120 bovine incisors. The bond of each specimen in eight randomly divided groups was tested to failure using an Instron Universal Testing Machine (Instron Corp, Canton, Mass). The mode of failure was evaluated using the adhesive remnant index (ARI)., Results: There were significant SBS differences between exposure times; 5-second exposures were significantly less than at 20-and 40-second exposures; SBS increased in a curvilinear fashion. Significant differences were recorded neither in the frequencies of ARI scores nor the SBS in relation to distance. Significant differences in the frequencies of ARI scores were observed when comparing the 5-second cure time to other time periods, indicating incomplete polymerization in the bracket base., Conclusions: SBS increased with increasing time periods in a curvilinear fashion, with no difference between the distances evaluated from source to specimen.

A novel lotion formulation of fluticasone propionate 0.05% has recently become available. Two large, randomized, placebo-controlled, double-blind studies involving 438 subjects demonstrated its efficacy and safety when applied once daily in the treatment of atopic dermatitis in subjects from 3 months to 87 years of age. The studies were limited to 4 weeks duration of use of fluticasone lotion and did not assess longer term efficacy or side effects.

This research sought to determine the shear bond strength, degree of resin infiltration and failure mode when organic solvent-based adhesives (acetone or ethanol) were used in immediate bonding to enamel bleached with 10% carbamide peroxide or 38% hydrogen peroxide systems. Seventy-two non-carious bovine incisors were randomly assigned to three groups of 24 specimens each-control group (deionized water), 38% hydrogen peroxide bleach group and 10% carbamide peroxide bleach group. Each group was further subdivided into two subgroups of 12 specimens each according to the adhesive system used to bond the resin composite to enamel surfaces. The two adhesive systems used were Single Bond, an ethanol-based adhesive, and One Step, an acetone-based adhesive. The shear bond strengths of 38% hydrogen peroxide and 10% carbamide peroxide were significantly lower compared to the non-bleached controls. Fractography revealed an adhesive failure mode in all specimens. Qualitative comparisons of resin tags present in the bleached and unbleached specimens using scanning electron microscopy (SEM) revealed few, thin and fragmented resin tags when 38% hydrogen peroxide and 10% carbamide peroxide were used.

Classic experiments have shown that ovulation and estrous cyclicity are under circadian control and that surgical ablation of the suprachiasmatic nuclei (SCN) results in estrous acyclicity in rats. Here, we characterized reproductive function in the circadian Clock mutant mouse and found that the circadian Clock mutation both disrupts estrous cyclicity and interferes with the maintenance of pregnancy. Clock mutant females have extended, irregular estrous cycles, lack a coordinated luteinizing hormone (LH) surge on the day of proestrus, exhibit increased fetal reabsorption during pregnancy, and have a high rate of full-term pregnancy failure. Clock mutants also show an unexpected decline in progesterone levels at midpregnancy and a shortened duration of pseudopregnancy, suggesting that maternal prolactin release may be abnormal. In a second set of experiments, we interrogated the function of each level of the hypothalamic-pituitary-gonadal (HPG) axis in order to determine how the Clock mutation disrupts estrous cyclicity. We report that Clock mutants fail to show an LH surge following estradiol priming in spite of the fact that hypothalamic levels of gonadotropin-releasing hormone (GnRH), pituitary release of LH, and serum levels of estradiol and progesterone are all normal in Clock/Clock females. These data suggest that Clock mutants lack an appropriate circadian daily-timing signal required to coordinate hypothalamic hormone secretion. Defining the mechanisms by which the Clock mutation disrupts reproductive function offers a model for understanding how circadian genes affect complex physiological systems.

Noncarious, cervical, wedge-shaped, sclerotic lesions are commonly encountered in clinical practice. In such lesions, dentin has been pathologically altered, often resulting in partial or complete obliteration of the dentinal tubules. These lesions are known to respond to etching and bonding differently from normal dentin, leading to complications during clinical treatment. A search of the literature was performed to obtain background information on the most commonly cited etiologic factors, clinical diagnoses, and morphologic and chemical characterizations along with an extensive review of all potential obstacles to bonding the most recent adhesives to such a dentinal substrate. Recent progress in adaptive strategies to render dentin more receptive to resin bonding is emphasized in this article, and the major drawbacks of these strategies are discussed.

Inducible nitric oxide synthase (iNOS) is a cytoplasmic protein responsible for the generation of nitric oxide (NO. ) in macrophages. In this work, we hypothesized that the intracellular localization of iNOS is significant for effective delivery of NO. to phagosomes containing ingested microorganisms. Using immunofluorescence microscopy and Western blot analysis, iNOS was shown to localize in the vicinity of phagosomes containing latex beads in stimulated macrophages. iNOS also localized to phagosomes containing Escherichia coli. The colocalization of iNOS with ingested latex beads was an actin-dependent process, since treatment with the actin microfilament disrupter cytochalasin D prevented iNOS recruitment to latex bead phagosomes. In contrast to E. coli and inert particle phagosomes, mycobacterial phagosomes did not colocalize with iNOS. This study demonstrates that (i). iNOS can be recruited to phagosomes; (ii). this recruitment is dependent on a functional actin cytoskeleton; (iii). certain microorganisms have the ability to prevent or reduce colocalization with iNOS; and (iv). spatial exclusion of iNOS may play a role in Mycobacterium tuberculosis pathogenesis.

Purpose: The purpose of this study was to compare internal Morse taper connections in 2 separate modes: repeated torque/reverse-torque values and compressive bending at a 30-degree off-axis angle., Materials and Methods: Three sample groups (n = 12 in each group)--a solid-screw implant paired with a 5.5-mm solid abutment (SSI), a synOcta implant with a 5.5-mm solid abutment (SOI), and a synOcta implant with a synOcta 5.5-mm solid abutment (SOSA)--were torqued to 35 Ncm, and the reverse torque to remove the abutment was recorded. This was repeated for 3 trials. Additionally, the sample groups were loaded 30 degrees off-axis, and the ultimate compressive values were recorded., Results: There was a significant difference in the initial reverse-torque values. The SOSA setup showed significantly lower torque than the SOI and SSI setups (P < .05). In addition, the compressive bending test showed that the SOSA setup was significantly different (P < .05) from the SSI and SOI setups. Radiographic survey of the test groups following compressive bending revealed no implant fractures, but bending of the implant-abutment complex occurred., Discussion: The alteration within the Morse taper did not reduce the strength of the implant-abutment connection, ie, the reduction in surface area did not significantly reduce the torque properties or tensile properties. The new 2-piece synOcta 5.5-mm solid abutment was shown to have a stronger implant-abutment connection when torqued down a second time., Conclusions: In this in vitro study, alteration of the Morse taper with an internal octagon indexing did not significantly reduce the strength of the implant connection. Sufficient strength was exhibited, which would indicate this implant-abutment design for anterior as well as posterior edentulous sites.

Statement of Problem: Amid increasing use of preparable ceramic implant abutments, there is a lack of quantitative data to show which abrasive particle size of diamond bur yields the fastest reduction and provides the smoothest surface., Purpose: The research aim was to determine the effects of diamond bur abrasive particle size and abutment material composition on preparation efficiency, prepared surface roughness, and surface deterioration of diamond burs., Material and Methods: Fifteen alumina (Cera Base) and 15 zirconia (ZiReal) implant abutments were each machined using a high-speed hand piece with a diamond bur having 1 of 3 abrasive particle sizes (150, 100, or 30 microm) (n=5). Control abutments (n=5) were analyzed without machining. Abutments were weighed before starting and between machining cycles. Three profilometry measurements (root mean square surface roughness) were made for each abutment. Scanning electron micrographs were made of each bur. Lost abrasive particles were then counted on each micrograph through a randomly placed template. Two-way analysis of variance (alpha=0.05) was used to test for significant effects., Results: Bur abrasive particle size and ceramic type had a significant interactive effect on the amount of material removed (P<.001). Super coarse (150 microm) burs yielded the roughest surfaces for each abutment material (P<.001), and prepared alumina surfaces were rougher than zirconia surfaces (P<.001). Super coarse burs showed the highest proportion of lost particles (P<.001). Abutment composition did not significantly affect bur wear., Conclusion: Super coarse burs yielded the most efficient material removal for alumina abutments. All abrasive particle sizes removed a similar amount of material from zirconia abutments. Fine-grained alumina abutments experienced greater material removal and rougher prepared surfaces compared with zirconia abutments. Material was removed by an intergranular fracture mechanism for alumina abutments, in contrast to transgranular fracture for zirconia abutments.

This study evaluated the shear-peel bond strength and mode of bond failure of 3 curing devices (plasma arc light, argon laser, and conventional halogen light) and 2 orthodontic bracket adhesives with different filler contents (Transbond XT and Adhesive Precoated [APC]). Observations of microleakage were also reported. Ninety human adolescent premolars were randomly divided into 6 groups, and standardized brackets were bonded according to the manufacturers' recommendations. The plasma arc light produced significantly (P =.006) higher bond strength than did the halogen light or the argon laser when Transbond was used. When APC was used, the plasma arc light and the halogen light produced similar results, and they both produced significantly (P =.015) higher bond strengths than did the argon laser. Overall, the APC showed substantially less variation in bond strength than did the Transbond. Although all curing methods showed significant microleakage (P <.001), differences among the 3 curing lights occurred only when APC was used. Microscopic evaluations demonstrated that 95% of the specimens failed for adhesion at the bracket or tooth surface; the argon laser produced the highest adhesive remnant index scores. On the basis of bond strength and microleakage results, the plasma arc light was comparable with or superior to the other curing devices, depending on the adhesive used.

During reproductive senescence in females, the function of GnRH neurons becomes compromised, and this may play a role in the transition from normal estrous cycles to acyclicity. One hypothalamic component of this dysregulation is an alteration in the stimulatory effects of glutamate, acting via N-methyl-D-aspartate receptors (NMDARs), on GnRH release. The present study examined whether GnRH neurons express the subunits necessary to make functional NMDARs, and how subunit expression may change during aging in association with compromised reproductive physiology. Colocalization of the three NMDAR subunits that are most abundant in the hypothalamus (NR1, NR2A, or NR2B) with GnRH perikarya was determined in female rats at different stages of the reproductive life cycle: young (3-4 months) rats with regular estrous cycles, middle-aged (8-10 months) rats with regular estrous cycles, middle-aged rats with irregular estrous cycles, and middle-aged acyclic rats in persistent estrus. The number, percent, and localization of GnRH perikarya expressing NR1, NR2A, or NR2B were mapped and quantified by double label immunofluorescence microscopy. Overall, each of the NMDAR subunits was present in a majority of GnRH neurons. There were no age- or reproductive status-related changes in coexpression of NR1 or NR2A subunits in GnRH neurons. However, coexpression of the NR2B subunit, which affects several functional channel characteristics, was significantly lower in young compared with middle-aged rats, irrespective of reproductive status. This may result in an age-related increase in the ratio of the NR2B to the NR1 and NR2A subunits on GnRH neurons. These data indicate that the majority of GnRH neurons express the proteins needed to receive direct NMDAR-mediated glutamatergic input, and that a change in the stoichiometry of the NMDAR pentamer occurs during aging that precedes, and may have consequences for, altered neuroendocrine function.

In mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed approximately 650 cycling transcripts and showed that the majority of these were specific to either the SCN or the liver. Genetic and genomic analysis suggests that a relatively small number of output genes are directly regulated by core oscillator components. Major processes regulated by the SCN and liver were found to be under circadian regulation. Importantly, rate-limiting steps in these various pathways were key sites of circadian control, highlighting the fundamental role that circadian clocks play in cellular and organismal physiology.

Adapalene gel 0.1% is approved for use in the treatment of acne vulgaris. A new cream formulation, adapalene cream 0.1%, has been developed. Our objective was to evaluate the efficacy and tolerability of adapalene cream 0.1% in comparison with its cream vehicle, applied once daily for 12 weeks to patients with facial acne vulgaris. We used a 12-week, multicenter, randomized, double-blind, vehicle-controlled, comparative phase 3 study of adapalene cream 0.1% and cream vehicle. The study enrolled 237 patients (125 males and 112 females), aged 12 through 30 years, with mild-to-moderate acne vulgaris. Adapalene cream 0.1% demonstrated superior efficacy compared with its cream vehicle. Significantly lower numbers of total inflammatory and noninflammatory lesion counts were observed at the end of the study period in patients using adapalene cream 0.1% as opposed to those using cream vehicle (P<.05 compared with baseline, for all 3 parameters). Adapalene cream 0.1% caused more cutaneous side effects than the cream vehicle, but these were tolerated in most patients. In summary, the results of this study indicate that adapalene cream 0.1% demonstrates superior efficacy over cream vehicle for the treatment of acne vulgaris. Adapalene cream 0.1% also has excellent tolerability and is associated with a low incidence of cutaneous adverse events.

Insulin-like growth factor-I (IGF-I) is thought to play a role in the onset of reproductive ability at puberty and the control of reproductive function throughout adult life. It is believed that these effects are mediated at least in part by the activation of gonadotropin releasing hormone (GnRH) neurones by IGF-I, but the interactions of IGF-I with GnRH neurones in vivo are largely unknown. We first examined the anatomical relationship between GnRH and IGF-I cells in neuroendocrine regions. Using double-label immunocytochemistry, we observed that in the preoptic area-anterior hypothalamus (POA-AH), the site of GnRH perikarya, the majority (78%) of GnRH cell bodies expressed IGF-I immunoreactivity. IGF-I immunoreactivity was also high in the median eminence, the site of GnRH release, and GnRH neuroterminals were seen to interweave among IGF-I-immunopositive cells. Due to this substantial overlap of GnRH and IGF-I immunoreactive elements, we then tested the hypothesis that changes in IGF-I may regulate the GnRH system. Animals were examined at the two important reproductive life transitions: puberty and reproductive senescence. IGF-I mRNA levels were measured in POA-AH and medial basal hypothalamus-median eminence (MBH-ME) and effects of IGF-I treatment on GnRH mRNA levels were quantified by RNase protection assay. Although IGF-I treatment did not alter GnRH gene expression, there were significant alterations in hypothalamic IGF-I gene expression at both puberty and reproductive senescence. During puberty, IGF-I mRNA levels in the MBH-ME of rats increased from the juvenile stage (P25) to the day of vaginal opening (P35), and from the day of vaginal opening to young adulthood (P45) in the POA-AH. During reproductive ageing, IGF-I mRNA levels were significantly lower in middle-aged than young rats, particularly in the MBH-ME. At all ages, IGF-I expression was greater in the MBH-ME than in the POA-AH. These experiments demonstrate that: (i) the majority of adult GnRH neurones are immunopositive for the IGF-I protein; (ii) hypothalamic IGF-I levels increase at the onset of reproductive function and decrease at reproductive senescence in a regionally specific manner; and (iii) despite the presence of IGF-I in GnRH perikarya, IGF-I does not affect GnRH gene expression, suggesting that IGF-I may act at the level of GnRH release rather than gene expression.

Statement of Problem: Chronic implant screw loosening remains a problem in restorative practices. Some implant manufacturers have introduced abutment screws with treated surfaces in an effort to increase preload and reduce potential loosening. Purpose. This study evaluated the materials and surfaces of 4 commercially available abutment screws on preload generation., Material and Methods: Twenty of each of the following abutment screws-Gold-Tite (Gt), TorqTite (Tt), gold alloy (Ga), and titanium alloy (Ta)-were divided into 2 groups. Measurements were recorded for each abutment screw on a mounted 3.75 x 18 mm external hex implant with a titanium abutment. Rotational angle measurements were conducted on the 4 abutment screws at 20 and 32 Ncm. Removal torque values were recorded and used to indirectly generate preload values. Random implant block specimens were sectioned and qualitatively evaluated with an SEM., Results: At 20 and 32 Ncm, the largest rotational angles were recorded for the Tt groups: 21.2 +/- 3.1 degrees and 38.1 +/- 8.7 degrees, respectively. The greatest preload values at 20 and 32 Ncm were calculated for the Gt groups: 596.8 +/- 101.2 N and 1015.3 +/- 191.2 N, respectively. SEM analysis of the 4 implant block specimens revealed mating thread contacts located in the middle portion of the superior surface of the abutment screw thread. The greatest number of mating thread contacts were seen in the Gt implant block specimen (14 of 20 possible thread contacts)., Conclusion: The Gt and Tt abutment screws with enhanced surfaces that help reduce the coefficient of friction produced greater rotational angles and preload values than the conventional gold alloy and titanium alloy screws.

Background: The ability of Mycobacterium tuberculosis to survive and replicate in macrophages is crucial for the mycobacterium's ability to infect the host and cause tuberculosis. To identify Mycobacterium tuberculosis genes involved in survival in macrophages, a library of non-pathogenic Mycobacterium smegmatis bacteria, each carrying an individual integrated cosmid containing M. tuberculosis H37Rv genomic DNA, was passed through THP-1 human macrophages three times., Results: Two of the clones recovered from this enrichment process, sur2 and sur3, exhibited significantly increased survival relative to wild-type bacteria. In coinfection experiments, the ratio of sur2 colonies to wild-type colonies was 1:1 at 0 hours but increased to 20:1 at 24 hours post phagocytosis. The ratio of sur3 colonies to wild-type colonies was 1:1 at 0 hours and 5:1 at 24 hours. The M. tuberculosis ORFs responsible for increased survival were shown to be Rv0365c for the sur2 clone and Rv2235 for the sur3 clone. These ORFs encode proteins with as-of-yet unknown functions., Conclusions: We identified two M. tuberculosis ORFs which may be involved in the ability of tubercle bacilli to survive in macrophages.

The purpose of this study was to evaluate the shear bond strength and the site of bond failure for 2 visible light-cured composites (Transbond XT and Enlight) and a resin-modified glass ionomer cement (RMGIC; Fuji Ortho LC). Seventy-five extracted human premolars were collected and randomly divided into 3 test groups. Brackets were bonded to the teeth in each test group with the respective adhesive according to the manufacturers' instructions. Each specimen was debonded using an Instron Universal Testing Machine at a crosshead speed of 0.1 mm/min. The mode of bond failure was observed by using light microscopy. The results of this study demonstrated that the light-cured composites had a higher shear bond strength than the RMGIC. The adhesive-remnant scores were similar for the composites with the mean values at about 2, which indicates that more than half of the adhesive remained on the tooth. The RMGIC had a mean score of 3, which was significantly different from the composites and indicated that all of the adhesive remained on the tooth with a distinct impression of the bracket.

A coinfection assay was developed to examine Mycobacterium tuberculosis genes suspected to be involved in resistance to killing by human macrophages. THP-1 macrophages were infected with a mixture of equal numbers of recombinant Mycobacterium smegmatis LR222 bacteria expressing an M. tuberculosis gene and wild-type M. smegmatis LR222 bacteria expressing the xylE gene. At various times after infection, the infected macrophages were lysed and the bacteria were plated. The resulting colonies were sprayed with catechol to determine the number of recombinant colonies and the number of xylE-expressing colonies. M. smegmatis bacteria expressing the M. tuberculosis glutamine synthetase A (glnA) gene or open reading frame Rv2962c or Rv2958c demonstrated significantly increased survival rates in THP-1 macrophages relative to those of xylE-expressing bacteria. M. smegmatis bacteria expressing M. tuberculosis genes for phospholipase C (plcA and plcB) or for high temperature requirement A (htrA) did not.