Effect of lithium carbonate on mouse and rat embryos in vitro

Lithium is effective in the treatment of manic-depressive psychosis but is suspected to be a developmental toxicant in humans. It is a developmental toxicant in mice and rats in vivo, but at human therapeutic serum levels of 0.6-1.6 meq/L, rats appear to be more sensitive to the effects of the drug than do mice. The species susceptibility to lithium-induced defects was evaluated by using a rodent whole embryo culture system employing mouse and rat embryos treated at comparable developmental stages. Mouse embryos were cultured on gestational days 8-10, and rat embryos were cultured on gestational days 10-12. Care was taken to insure that all embryos had 10 +/- 2 somite pairs at the beginning of the culture period. Embryos were cultured for 44 hours in rat serum to which lithium was added to attain final drug concentrations of 0.6, 1.2, 1.8, 2.4, or 5.0 meq/L. Control embryos were treated with distilled water, which served as the vehicle. In rats, lithium induced significant decreases in various parameters at 1.8, 2.4, and 5.0 meq/L; no malformations were observed in rats of this stage. In mice, significant decreases occurred at 2.4 and 5.0 meq/L, and embryos treated at the highest concentration had a significantly increased frequency of open neural tubes. Rat embryos were also cultured with lithium on gestational days 9-11. The lowest dose producing developmental toxicity at this stage was 0.6 meq/L. Open neural tubes were present among younger rat embryos; however, this defect occurred in all groups, including the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic Analysis of Two Allelic Temperature-Sensitive Mutants of DROSOPHILA MELANOGASTER Both of Which Are Zygotic and Maternal-Effect Lethals

After fertilization, the development of a zygote depends upon both gene products synthesized by its maternal parent and gene products synthesized by the zygote itself. To analyze genetically the relative contributions of these two sources of gene products, several laboratories have been isolating two classes of mutants of Drosophila melanogaster: maternal-effect lethals and zygotic lethals. This report concerns the analysis of two temperature-sensitive mutants, OX736hs and PC025hs, which were isolated as alleles of a small-disc mutant, l(3)1902. These alleles are not only zygotic lethals, but also maternal-effect lethals. They have temperature-sensitive periods during larval life and during oogenesis. Mutant larvae exposed continuously to restrictive temperature have small discs. One-or two-day exposures to the restrictive temperature administered during the third larval instar lead to a homeotic transformation of the midlegs and hindlegs to the pattern characteristic of the forelegs. Mutant females exposed to the restrictive temperature during oogenesis produce eggs that can develop until gastrulation, but do not hatch.--The existence of these mutants, and one that was recently described by another group, implies that there may be a class of genes, heretofore unrecognized, whose products are synthesized during oogenesis, are essential for embryogenesis and are also synthesized during larval stages within imaginal disc cells.     

Task-Based Core-Periphery Organization of Human Brain Dynamics

As a person learns a new skill, distinct synapses, brain regions, and circuits are engaged and change over time. In this paper, we develop methods to examine patterns of correlated activity across a large set of brain regions. Our goal is to identify properties that enable robust learning of a motor skill. We measure brain activity during motor sequencing and characterize network properties based on coherent activity between brain regions. Using recently developed algorithms to detect time-evolving communities, we find that the complex reconfiguration patterns of the brain''s putative functional modules that control learning can be described parsimoniously by the combined presence of a relatively stiff temporal core that is composed primarily of sensorimotor and visual regions whose connectivity changes little in time and a flexible temporal periphery that is composed primarily of multimodal association regions whose connectivity changes frequently. The separation between temporal core and periphery changes over the course of training and, importantly, is a good predictor of individual differences in learning success. The core of dynamically stiff regions exhibits dense connectivity, which is consistent with notions of core-periphery organization established previously in social networks. Our results demonstrate that core-periphery organization provides an insightful way to understand how putative functional modules are linked. This, in turn, enables the prediction of fundamental human capacities, including the production of complex goal-directed behavior.     

Predisposition for venoconstriction in the equine laminar dermis: implications in equine laminitis.

Equine laminitis is a crippling condition associated with a variety of systemic diseases. Although it is apparent that the prodromal stages of laminitis involve microvascular dysfunction, little is known regarding the physiology of this vasculature. The aim of the present study was to determine the relative responses of equine laminar arteries and veins to the vasoconstrictor agonists phenylephrine (1 nM-10 microM), 5-HT (1 nM-10 microM), PGF2alpha (1 nM-100 microM), and endothelin-1 (1 pM-1 microM). We have determined that laminar veins were more sensitive, with respect to the concentration of agonist required to initiate a contractile response and to achieve EC(50), for all agonists tested. EC50 values, for veins and arteries, respectively, were 84+/-7 vs. 688+/-42 nM for phenylephrine, 35+/-6 vs. 224+/-13 nM for 5-HT, 496+/-43 nM vs. 3.0+/-0.6 microM for PGF2alpha, and 467+/-38 pM vs. 70.6+/-6.4 nM for endothelin-1. Moreover, when expressed as a percentage of the response to a depolarizing stimulus (80 mM potassium), the maximal contractile response of laminar veins exceeded that for the laminar arteries for each agonist. These results indicate that there may be a predisposition for venoconstriction within the vasculature of the equine digit. While this physiological predisposition for venoconstriction may be important in the regulation of blood flow during exercise, it also may help to explain why laminitis can result from a variety of pathological systemic conditions.     

Differential recruitment of the sensorimotor putamen and frontoparietal cortex during motor chunking in humans

Motor chunking facilitates movement production by combining motor elements into integrated units of behavior. Previous research suggests that chunking involves two processes: concatenation, aimed at the formation of motor-motor associations between elements or sets of elements, and segmentation, aimed at the parsing of multiple contiguous elements into shorter action sets. We used fMRI to measure the trial-wise recruitment of brain regions associated with these chunking processes as healthy subjects performed a cued-sequence production task. A dynamic network analysis identified chunking structure for a set of motor sequences acquired during fMRI and collected over 3?days of training. Activity in the bilateral sensorimotor putamen positively correlated with chunk concatenation, whereas?a left-hemisphere frontoparietal network was correlated with chunk segmentation. Across subjects, there was an aggregate increase in chunk strength (concatenation) with training, suggesting that subcortical circuits play a direct role in the creation of fluid transitions across chunks.     

Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma Mechanics

This article presents the integration of brain injury biomechanics and graph theoretical analysis of neuronal connections, or connectomics, to form a neurocomputational model that captures spatiotemporal characteristics of trauma. We relate localized mechanical brain damage predicted from biofidelic finite element simulations of the human head subjected to impact with degradation in the structural connectome for a single individual. The finite element model incorporates various length scales into the full head simulations by including anisotropic constitutive laws informed by diffusion tensor imaging. Coupling between the finite element analysis and network-based tools is established through experimentally-based cellular injury thresholds for white matter regions. Once edges are degraded, graph theoretical measures are computed on the "damaged" network. For a frontal impact, the simulations predict that the temporal and occipital regions undergo the most axonal strain and strain rate at short times (less than 24 hrs), which leads to cellular death initiation, which results in damage that shows dependence on angle of impact and underlying microstructure of brain tissue. The monotonic cellular death relationships predict a spatiotemporal change of structural damage. Interestingly, at 96 hrs post-impact, computations predict no network nodes were completely disconnected from the network, despite significant damage to network edges. At early times ([Formula: see text]) network measures of global and local efficiency were degraded little; however, as time increased to 96 hrs the network properties were significantly reduced. In the future, this computational framework could help inform functional networks from physics-based structural brain biomechanics to obtain not only a biomechanics-based understanding of injury, but also neurophysiological insight.     

BICAR: A New Algorithm for Multiresolution Spatiotemporal Data Fusion

We introduce a method for spatiotemporal data fusion and demonstrate its performance on three constructed data sets: one entirely simulated, one with temporal speech signals and simulated spatial images, and another with recorded music time series and astronomical images defining the spatial patterns. Each case study is constructed to present specific challenges to test the method and demonstrate its capabilities. Our algorithm, BICAR (Bidirectional Independent Component Averaged Representation), is based on independent component analysis (ICA) and extracts pairs of temporal and spatial sources from two data matrices with arbitrarily different spatiotemporal resolution. We pair the temporal and spatial sources using a physical transfer function that connects the dynamics of the two. BICAR produces a hierarchy of sources ranked according to reproducibility; we show that sources which are more reproducible are more similar to true (known) sources. BICAR is robust to added noise, even in a “worst case” scenario where all physical sources are equally noisy. BICAR is also relatively robust to misspecification of the transfer function. BICAR holds promise as a useful data-driven assimilation method in neuroscience, earth science, astronomy, and other signal processing domains.     

The Influence of Weekday Eating Patterns on Energy Intake and BMI Among Female Elementary School Personnel

Many health practitioners recommend eating small, frequent meals for weight loss, yet the relationship of eating patterns, such as eating occasion frequency (EOF), to energy intake and body weight is controversial. Broad‐based efforts to promote worksite wellness programs increase the importance of this issue, as many work environments inherently restrict eating patterns. The eating patterns of school personnel are understudied, but are of particular interest, not only because they have limited eating opportunities during the day but also because their diet and weight outcomes are likely to influence behaviors of a much larger population. We examined relationships between weekday EOF and energy intake and BMI among female elementary school personnel in 22 schools in a suburban county of southeastern Louisiana. Two 24‐h dietary recalls were administered to randomly‐selected employees (n = 329) on nonconsecutive days by registered dietitians. Measured heights and weights were used to calculate BMI (weight/height²). On average, employees consumed 2.2 of their total 5.9 meals and snacks during the school day, accounting for 37% of daily energy. In multiple regression models controlling for demographic and health variables, EOF as well as separate counts of meal and snack frequency were each positively and significantly associated with energy intake. However, neither the number of meals, snacks, nor overall EOF was associated with BMI. The proportion of energy consumed during the school day and the positive association of weekday EOF with energy intake suggest an important role for worksite wellness programs that target the dietary improvement of elementary school personnel.