On the symmetry of limb deficiencies among children with multiple congenital anomalies

In humans, unpaired organs are placed in a highly ordered pattern along the left-right axis. As indicated by animal studies, a cascade of signaling molecules establish left-right asymmetry in the developing embryo. Some of the same genes are involved also in limb patterning. To provide a better insight into the connection between these processes in humans, we analysed the symmetry of limb deficiencies among infants with multiple congenital anomalies. The study was based on data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). Registries of the ICBDMS provided information on infants who, in addition to a limb deficiency, also had at least one major congenital anomaly in other organ systems. We reviewed 815 such cases of which 149 cases (18.3 %) were syndromic and 666 (81.7 %) were nonsyndromic. The comparisons were made within the associated limb deficiencies, considering the information on symmetry, using a comparison group with malformations associated not involved in the index association. Among the non-syndromic cases, the left-right distribution of limb deficiencies did not differ appreciably between limb deficiency subtypes (e.g., preaxial, transverse, longitudinal). The left-right distribution of limb anomalies did not differ among most types of non-limb anomalies, though a predominance of left-sided limb deficiencies was observed in the presence of severe genital defects - odds ratio [OR], 2.6; 95 % CI, 1.1-6.4). Limb deficiencies (LDs) were more often unilateral than bilateral when accompanied by gastroschisis (OR, 0.1) or axial skeletal defects (OR, 0.5). On the contrary, LDs were more often bilateral than unilateral when associated with cleft lip with or without cleft palate (OR, 3.9) or micrognathia (OR, 2.6). Specifically, we found an association between bilateral preaxial deficiencies and cleft lip, bilateral amelia with gastroschisis and urinary tract anomalies, and bilateral transverse deficiencies and gastroschisis and axial skeleton defects. Of 149 syndromic cases, 62 (41.6 %) were diagnosed as trisomy 18. Out of the 30 cases of trisomy 18 with known laterality, 20 cases were bilateral. In the remainder the right and left sides were equally affected. Also, in most cases (74.4 %) only the upper limbs were involved. In conclusion the left-right distribution of limb deficiencies among some non-limb anomalies may suggest a relationship between the development of the limb and the left-right axis of the embryo.     

Citrullination, a possible functional link between susceptibility genes and rheumatoid arthritis

Antibodies directed to citrullinated proteins (anti-cyclic citrullinated peptide) are highly specific for rheumatoid arthritis (RA). Recent data suggest that the antibodies may be involved in the disease process of RA and that several RA-associated genetic factors might be functionally linked to RA via modulation of the production of anti-cyclic citrullinated peptide antibodies or citrullinated antigens.     

Redox modulation of T-type calcium channels in rat peripheral nociceptors

Although T-type calcium channels were first described in sensory neurons, their function in sensory processing remains unclear. In isolated rat sensory neurons, we show that redox agents modulate T currents but not other voltage- and ligand-gated channels thought to mediate pain sensitivity. Similarly, redox agents modulate currents through Ca(v)3.2 recombinant channels. When injected into peripheral receptive fields, reducing agents, including the endogenous amino acid L-cysteine, induce thermal hyperalgesia. This hyperalgesia is blocked by the oxidizing agent 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) and the T channel antagonist mibefradil. DTNB alone and in combination with mibefradil induces thermal analgesia. Likewise, L-cysteine induces mechanical DTNB-sensitive hyperalgesia in peripheral receptive fields. These data strongly suggest a role for T channels in peripheral nociception. Redox sites on T channels in peripheral nociceptors could be important targets for agents that modify pain perception.     

Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats

Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P) rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total) or were given access only to water (control). Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4)-desaturase (Degs2), an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels achieved by alcohol-preferring P rats as a result of chronic voluntary exposure may have favorable vs. detrimental effects on lipid profiles in this genetic line, consistent with data supporting beneficial cardioprotective and neuroprotective effects of moderate ethanol consumption.     

Motion Tracker: Camera-Based Monitoring of Bodily Movements Using Motion Silhouettes

Researchers in the cognitive and affective sciences investigate how thoughts and feelings are reflected in the bodily response systems including peripheral physiology, facial features, and body movements. One specific question along this line of research is how cognition and affect are manifested in the dynamics of general body movements. Progress in this area can be accelerated by inexpensive, non-intrusive, portable, scalable, and easy to calibrate movement tracking systems. Towards this end, this paper presents and validates Motion Tracker, a simple yet effective software program that uses established computer vision techniques to estimate the amount a person moves from a video of the person engaged in a task (available for download from http://jakory.com/motion-tracker/). The system works with any commercially available camera and with existing videos, thereby affording inexpensive, non-intrusive, and potentially portable and scalable estimation of body movement. Strong between-subject correlations were obtained between Motion Tracker’s estimates of movement and body movements recorded from the seat (r =.720) and back (r = .695 for participants with higher back movement) of a chair affixed with pressure-sensors while completing a 32-minute computerized task (Study 1). Within-subject cross-correlations were also strong for both the seat (r =.606) and back (r = .507). In Study 2, between-subject correlations between Motion Tracker’s movement estimates and movements recorded from an accelerometer worn on the wrist were also strong (rs = .801, .679, and .681) while people performed three brief actions (e.g., waving). Finally, in Study 3 the within-subject cross-correlation was high (r = .855) when Motion Tracker’s estimates were correlated with the movement of a person’s head as tracked with a Kinect while the person was seated at a desk (Study 3). Best-practice recommendations, limitations, and planned extensions of the system are discussed.     

Arabidopsis Contains at Least Four Independent Blue-Light-Activated Signal Transduction Pathways

We have investigated the stomatal and phototropic responses to blue light of a number of single and double mutants at various loci that encode proteins involved in blue-light responses in Arabidopsis. The stomatal responses of light-grown mutant plants (cry1, cry2, nph1, nph3, nph4, cry1cry2, and nph1cry1) did not differ significantly from those of their wild-type counterparts. Second positive phototropic responses of etiolated mutant seedlings, cry1, cry2, cry1cry2, and npq1-2, were also similar to those of their wild-type counterparts. Although npq1 and single and double cry1cry2 mutants showed somewhat reduced amplitude for first positive phototropism, threshold, peak, and saturation fluence values for first positive phototropic responses of etiolated seedlings did not differ from those of wild-type seedlings. Similar to the cry1cry2 double mutants and to npq1-2, a phyAphyB mutant showed reduced curvature but no change in the position or shape of the fluence-response curve. By contrast, the phototropism mutant nph1-5 failed to show phototropic curvature under any of the irradiation conditions used in the present study. We conclude that the chromoproteins cry1, cry2, nph1, and the blue-light photoreceptor for the stomatal response are genetically separable. Moreover, these photoreceptors appear to activate separate signal transduction pathways.     

Cerebral metabolic response to systematic kainic acid: 14-C-deoxyglucose studies

Kainic acid (KA) given once intravenously in a dose of 12 mg/kg results successively in staring spells, wet dog shakes, and overt behavioral convulsions over a 90 minute time period. Convulsions last up to 18 hours and are followed by aphagia, adipsia and startle. behavior. Five minutes after KA, deoxyglucose autoradiography reveals a 3–6 fold increase in glucose utilization in ventral CA3 of hippocampus, ventral subiculum, lateral septum with a less intense increase in dorsal hippocampus. During severe behavioral convulsions the entire limbic system and its subcortical projections are metabolically active, while sensory pathways and neocortex are depressed. One to three days following convulsions many limbic areas that participated in seizures are necrotic, while metabolism in the rest of the brain has returned toward normal.     

Periconceptional maternal alcohol consumption and neural tube defects

BACKGROUND: Neural tube defects (NTD)s, which occur when the neural tube fails to close during early gestation, are some of the most common birth defects worldwide. Alcohol is a known teratogen and has been shown to induce NTDs in animal studies, although most human studies have failed to corroborate these results. Using data from the National Birth Defects Prevention Study, associations between maternal reports of periconceptional (1 month prior through 2 months postconception) alcohol consumption and NTDs were examined. METHODS: NTD cases and unaffected live born control infants, delivered from 1997 through 2005, were included. Interview reports of alcohol consumption (quantity, frequency, variability, and type) were obtained from 1223 case mothers and 6807 control mothers. Adjusted odds ratios (aOR)s and 95% confidence intervals were estimated using multivariable logistic regression analysis. RESULTS: For all NTDs combined, most aORs for any alcohol consumption, one or more binge episodes, and different type(s) of alcohol consumed were near unity or modestly reduced (≥0.7<aOR≤1.1) and were not statistically significant. Findings were similar for individual NTD subtypes. CONCLUSIONS: These findings suggest no elevated association between maternal periconceptional alcohol consumption and NTDs. Underreporting of alcohol consumption, due to negative social stigma associated with alcohol consumption during pregnancy, and limited reports for mothers with early pregnancy loss of a fetus with an NTD may have affected the estimated odds ratios. Future studies should aim to increase sample sizes for less prevalent subtypes, reduce exposure misclassification, and improve ascertainment offetal deaths and elective terminations. Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.