Discordant growth of nasal cartilage and bone contributes to phenotypic variability of the skull in a mouse model.

BACKGROUND: We previously determined a nonlinear relationship between connexin 43 (Cx43) function and craniofacial phenotypic variation in the mutant mouse model G60S/+, and that this variation was driven by nasal bone deviation. While nonlinearities in the genotype-phenotype map appear to be common, few studies have looked at the developmental processes that underlie this nonlinearity. Here, we investigated the potential tissue-level developmental determinants of the variation in nasal bone phenotype in G60S/+ mice through postnatal development. RESULTS: The deviated nasal bone phenotype arises by postnatal day 21 and becomes more severe by 3 months in G60S/+ mice. Measures of nasal bone remodeling including the number of osteoclasts, mineralizing surface, mineral apposition rate, and bone formation rate are significantly greater in G60S/+ mice compared to wild-type mice at 2 months, but these differences do not correspond with nasal bone deviation. The degree of nasal bone deviation does significantly and negatively correlate with the ratio between nasal bone and cartilaginous nasal septum length. CONCLUSIONS: Our findings indicate that the mean phenotypic changes observed between G60S/+ and wild-type mice are due to reduced bone growth, but the increased phenotypic variation found within mutant mice is due to discordant growth between nasal cartilage and bone.

Effects of Reduced Connexin43 Function on Mandibular Morphology and Osteogenesis in Mutant Mouse Models of Oculodentodigital Dysplasia.

Mutations in the gene encoding the gap-junctional protein connexin43 (Cx43) are the cause of the human disease oculodentodigital dysplasia (ODDD). The mandible is often affected in this disease, with clinical reports describing both mandibular overgrowth and conversely, retrognathia. These seemingly opposing observations underscore our relative lack of understanding of how ODDD affects mandibular morphology. Using two mutant mouse models that mimic the ODDD phenotype (I130T/+ and G60S/+), we sought to uncover how altered Cx43 function may affect mandibular development. Specifically, mandibles of newborn mice were imaged using micro-CT, to enable statistical comparisons of shape. Tissue-level comparisons of key regions of the mandible were conducted using histomorphology, and we quantified the mRNA expression of several cartilage and bone cell differentiation markers. Both G60S/+ and I130T/+ mutant mice had altered mandibular morphology compared to their wildtype counterparts, and the morphological effects were similarly localized for both mutants. Specifically, the biggest phenotypic differences in mutant mice were focused in regions exposed to mechanical forces, such as alveolar bone, muscular attachment sites, and articular surfaces. Histological analyses revealed differences in ossification of the intramembranous bone of the mandibles of both mutant mice compared to their wildtype littermates. However, chondrocyte organization within the secondary cartilages of the mandible was unaffected in the mutant mice. Overall, our results suggest that the morphological differences seen in G60S/+ and I130T/+ mouse mandibles are due to delayed ossification and suggest that mechanical forces may exacerbate the effects of ODDD on the skeleton.

Emotion Reactivity, Comfort Expressing Emotions, and Future Suicidal Ideation in Emerging Adults.

OBJECTIVE: Emotion reactivity and difficulties in expressing emotions have been implicated in risk for suicidal behavior. This study examined comfort in expressing emotions (positive vs. negative) and depressive symptoms as mediators of the prospective relation between emotion reactivity and suicidal ideation. DESIGN: Emerging adults (N = 143; 72% female; 28% White) completed measures of emotion reactivity, comfort expressing emotions, and suicidal ideation at baseline and of depressive symptoms and suicidal ideation 12 months later. RESULTS: Emotion reactivity predicted suicidal ideation at follow-up through depressive symptoms. Difficulty expressing love-but not happiness, sadness, and anger-partially mediated the relationship between emotion reactivity and suicidal ideation at follow-up before but not after adjusting for baseline ideation. CONCLUSION: The relation between high emotion reactivity and suicidal ideation may be explained by discomfort in the expression of positive emotions and by depressive symptoms. Promotion of comfort in positive emotion expression may reduce vulnerability to suicidal ideation.

Resveratrol and Depression in Animal Models: A Systematic Review of the Biological Mechanisms.

Depression is currently treated by pharmacotherapies that can elicit debilitating side effects for patients. Novel treatment options with limited side effects are currently being researched. Resveratrol is a polyphenol and phytoalexin found in the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been studied extensively for its antioxidant and anti-inflammatory properties. Resveratrol has also gained attention for its neuroprotective properties. The aim of the review was to examine the mechanisms by which resveratrol reduces depressive behaviors in animal models. In total, 22 studies met the established criteria for final review. Behavioral aspects of depression were investigated using validated measures such as the forced swimming test, tail suspension test, sucrose preference test, and open field test. While many physical measures were taken, three main biological mechanisms were explored: Regulation of the hypothalamic⁻pituitary⁻adrenal axis; decreased inflammation; and increased Brain-Derived Neurotrophic Factor and neurogenesis. Based on these findings, resveratrol may be deemed an effective treatment for depression in animal models at doses between 10⁻80 mg/kg/day, although higher doses had the most significant effects. Future studies should examine the effects of resveratrol on depression in humans to determine the eligibility of resveratrol as a natural antidepressant with less severe side effects.

Imaging of N-Linked Glycans in Biological Tissue Sections Using Nanospray Desorption Electrospray Ionization (nano-DESI) Mass Spectrometry.

N-linked glycans are complex biomolecules vital to cellular functions that have been linked to a wide range of pathological conditions. Mass spectrometry imaging (MSI) has been used to study the localization of N-linked glycans in cells and tissues. However, their structural diversity presents a challenge for MSI techniques, which stimulates the development of new approaches. In this study, we demonstrate for the first time spatial mapping of N-linked glycans in biological tissues using nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI). Nano-DESI MSI is an ambient ionization technique that has been previously used for imaging of metabolites, lipids, and proteins in biological tissue samples without special sample pretreatment. N-linked glycans are released from glycoproteins using an established enzymatic digestion with peptide N-glycosidase F, and their spatial localization is examined using nano-DESI MSI. We demonstrate imaging of N-linked glycans in formalin-fixed paraffin-embedded human hepatocellular carcinoma and human prostate tissues in both positive and negative ionization modes. We examine the localization of 38 N-linked glycans consisting of high mannose, hybrid fucosylated, and sialyated glycans. We demonstrate that negative mode nano-DESI MSI is well-suited for imaging of underivatized sialylated N-linked glycans. On-tissue MS/MS of different adducts of N-linked glycans proves advantageous for elucidation of the glycan sequence. This study demonstrates the applicability of liquid extraction techniques for spatial mapping of N-linked glycans in biological samples, providing an additional tool for glycobiology research.

Syn3 Gene Knockout Negatively Impacts Aspects of Reversal Learning Performance.

Behavioral flexibility enables the ability to adaptively respond to changes in contingency requirements to maintain access to desired outcomes, and deficits in behavioral flexibility have been documented in many psychiatric disorders. Previous research has shown a correlation between behavioral flexibility measured in a reversal learning test and Syn3, the gene encoding synapsin III, which negatively regulates phasic dopamine release. Syn3 expression in the hippocampus, striatum, and neocortex is reported to be negatively correlated with reversal learning performance, so here, we used a global knock-out line to investigate reversal learning in mice homozygous wild type, heterozygous null, and homozygous null for the Syn3 gene. Compared with wild-type animals, we found a reversal-specific effect of genetic Syn3 deficiency that resulted in a greater proportional increase in trials required to reach a preset performance criterion during contingency reversal, despite no observed genotype effects on the ability to acquire the initial discrimination. Behavioral flexibility scores, which quantified the likelihood of switching subsequent choice behavior following positive or negative feedback, became significantly more negative in reversal only for Syn3 homozygous-null mice, suggesting a substantial increase in perseverative behavior in the reversal phase. Syn3 ablation reduced the number of anticipatory responses made per trial, often interpreted as a measure of waiting impulsivity. Overall, Syn3 expression negatively affected behavioral flexibility in a reversal-specific manner but may have reduced waiting impulsivity.

The effects of force requirements on microstructure: Subcriterion responses and the mismeasurement of bouts.

The effects of response force on microstructure were evaluated. A strain-gauge operandum permitted the manipulation of the force required to produce reinforcers (criterion responses) independently from the force defining response threshold. Thus, we could detect subcriterion forces that fell short of the force criterion. Eight rats earned food according to variable-interval (VI) 30- and 120-s schedules. The force requirements were set to 5.6 or 32.0 g; the response threshold was fixed at 5.6 g. Interresponse times were computed when subcriterion responses were both included and omitted from the analysis. Log-survivor functions of interresponse times showed that increasing force requirements elevated the mean between-bout interval of the VI 120-s schedule, but only if subcriterion behavior was excluded. Omitting subcriterion responses thus leads to overestimation of intervals separating response bouts. Increasing force requirements also increased the skewness of the between-bout distribution. A subsequent analysis found that subcriterion responses are most plentiful following reinforcer delivery, which helps to explain why their omission might inflate between-bout intervals, as this period is an important transition from reinforcer consumption to engagement in operant activity. The data suggest caution interpreting the effects of force on microstructure when subcriterion behavior is not or cannot be measured.

Amputation Following Hand Escharotomy in Patients with Burn Injury.

OBJECTIVE: Hand burns are commonly seen in patients with burn injury. In the past, focus was on lifesaving measures, but with advances in burn care during the last century, the paradigm shifted to digital salvage and eventually to functional digital salvage. Good outcomes are heavily dependent on the care that is rendered during the initial management of the burn. METHODS: A retrospective medical record review was conducted through the Central Illinois Regional Burn Center Patient Registry. Patients with burn injury treated with upper extremity and hand escharotomy between January 1, 2000, and December 31, 2005, were included in the study. RESULTS: We identified a total of 34 patients with 57 burned hands. Six hands required delayed amputation of digits despite recognition of neurovascular compromise and escharotomy, yielding a 10% amputation rate. No correlation could be drawn with regard to total body surface area, age, or sex. CONCLUSION: Important principles in the acute phase include early splinting, recognition of the need for escharotomy and complete escharotomy when necessary, early excision and grafting, and involvement of occupational therapy for splinting and to guide both active and passive exercises. Although uncommon, some extremity burns may require subsequent amputation despite prompt attention and optimal treatment. In our case series, the need for amputation after successful escharotomies of salvageable digits was associated with full-thickness and electrical burns.

Bioinformatics Resources for MicroRNA Discovery.

Biomarker identification is often associated with the diagnosis and evaluation of various diseases. Recently, the role of microRNA (miRNA) has been implicated in the development of diseases, particularly cancer. With the advent of next-generation sequencing, the amount of data on miRNA has increased tremendously in the last decade, requiring new bioinformatics approaches for processing and storing new information. New strategies have been developed in mining these sequencing datasets to allow better understanding toward the actions of miRNAs. As a result, many databases have also been established to disseminate these findings. This review focuses on several curated databases of miRNAs and their targets from both predicted and validated sources.

Mental Health Treatment Barriers Among Racial/Ethnic Minority Versus White Young Adults 6 Months After Intake at a College Counseling Center.

OBJECTIVE: This study examined mental health treatment barriers following intake at a counseling center among racially/ethnically diverse college students. METHODS: College students (N = 122) seen for intake at a college counseling center in 2012-2013 completed self-reports of depressive symptoms, suicidal ideation, and mental health treatment barriers 6 months later. RESULTS: Racial/ethnic minority students less often reported previous mental health treatment and treatment after being seen at the counseling center, compared with white students. They also endorsed more treatment barriers--most commonly, financial concerns and lack of time--and more often endorsed stigma-related concerns. Treatment barriers were associated with not following through with counseling center recommendations and with greater depressive symptom severity but not with suicidal ideation during follow-up. CONCLUSIONS: Improving mental health treatment seeking among racial/ethnic minority college students should involve decreasing treatment barriers, improving access to affordable options, providing flexible scheduling or time-limited options, and decreasing stigma.