Developmental learning impairments in a rodent model of nodular heterotopia

Developmental malformations of neocortex—including microgyria, ectopias, and periventricular nodular heterotopia (PNH)—have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21–42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60–100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans

Backward walking training improves balance in school-aged boys

<p>Abstract</p> <p>Background</p> <p>Falls remain a major cause of childhood morbidity and mortality. It is suggested that backward walking (BW) may offer some benefits especially in balance and motor control ability beyond those experienced through forward walking (FW), and may be a potential intervention for prevention of falls. The objective of this study was to investigate the effects of BW on balance in boys.</p> <p>Methods</p> <p>Sixteen healthy boys (age: 7.19 ± 0.40 y) were randomly assigned to either an experimental or a control group. The experimental group participated in a BW training program (12-week, 2 times weekly, and 25-min each time) but not the control group. Both groups had five dynamic balance assessments with a Biodex Stability System (anterior/posterior, medial/lateral, and overall balance index) before, during and after the training (week- 0, 4, 8, 12, 24). Six control and six experimental boys participated in a study comparing kinematics of lower limbs between FW and BW after the training (week-12).</p> <p>Results</p> <p>The balance of experimental group was better than that of control group after 8 weeks of training (<it>P </it>< 0.01), and was still better than that of control group (<it>P </it>< 0.05), when the BW training program had finished for 12 weeks. The kinematic analysis indicated that there was no difference between control and experimental groups in the kinematics of both FW and BW gaits after the BW training (<it>P </it>> 0.05). Compared to FW, the duration of stance phase of BW tended to be longer, while the swing phase, stride length, walking speed, and moving ranges of the thigh, calf and foot of BW decreased (<it>P </it>< 0.01).</p> <p>Conclusion</p> <p>Backward walking training in school-aged boys can improve balance.</p

A Common Variant Associated with Dyslexia Reduces Expression of the KIAA0319 Gene

Numerous genetic association studies have implicated the KIAA0319 gene on human chromosome 6p22 in dyslexia susceptibility. The causative variant(s) remains unknown but may modulate gene expression, given that (1) a dyslexia-associated haplotype has been implicated in the reduced expression of KIAA0319, and (2) the strongest association has been found for the region spanning exon 1 of KIAA0319. Here, we test the hypothesis that variant(s) responsible for reduced KIAA0319 expression resides on the risk haplotype close to the gene's transcription start site. We identified seven single-nucleotide polymorphisms on the risk haplotype immediately upstream of KIAA0319 and determined that three of these are strongly associated with multiple reading-related traits. Using luciferase-expressing constructs containing the KIAA0319 upstream region, we characterized the minimal promoter and additional putative transcriptional regulator regions. This revealed that the minor allele of rs9461045, which shows the strongest association with dyslexia in our sample (max p-value = 0.0001), confers reduced luciferase expression in both neuronal and non-neuronal cell lines. Additionally, we found that the presence of this rs9461045 dyslexia-associated allele creates a nuclear protein-binding site, likely for the transcriptional silencer OCT-1. Knocking down OCT-1 expression in the neuronal cell line SHSY5Y using an siRNA restores KIAA0319 expression from the risk haplotype to nearly that seen from the non-risk haplotype. Our study thus pinpoints a common variant as altering the function of a dyslexia candidate gene and provides an illustrative example of the strategic approach needed to dissect the molecular basis of complex genetic traits

A New Direction to Athletic Performance: Understanding the Acute and Longitudinal Responses to Backward Running

Backward running (BR) is a form of locomotion that occurs in short bursts during many overground field and court sports. It has also traditionally been used in clinical settings as a method to rehabilitate lower body injuries. Comparisons between BR and forward running (FR) have led to the discovery that both may be generated by the same neural circuitry. Comparisons of the acute responses to FR reveal that BR is characterised by a smaller ratio of braking to propulsive forces, increased step frequency, decreased step length, increased muscle activity and reliance on isometric and concentric muscle actions. These biomechanical differences have been critical in informing recent scientific explorations which have discovered that BR can be used as a method for reducing injury and improving a variety of physical attributes deemed advantageous to sports performance. This includes improved lower body strength and power, decreased injury prevalence and improvements in change of direction performance following BR training. The current findings from research help improve our understanding of BR biomechanics and provide evidence which supports BR as a useful method to improve athlete performance. However, further acute and longitudinal research is needed to better understand the utility of BR in athletic performance programs

Estimating population birth rates of zooplankton when rates of egg deposition and hatching are periodic

I present a general method of computing finite birth and death rates of natural zooplankton populations from changes in the age distribution of eggs and changes in population size. The method is applicable to cases in which eggs hatch periodically owing to variable rates of oviposition. When morphological criteria are used to determine the age distribution of eggs at the beginning and end of a sampling interval, egg mortality can be incorporated in estimates of population birth rate. I raised laboratory populations of Asplanchna priodonta , a common planktonic rotifer, in semicontinuous culture to evaluate my method of computing finite birth rate. The Asplanchna population became synchronized to a daily addition of food but grew by the same amount each day once steady state was achieved. The steady-state rate of growth, which can be computed from the volume-specific dilution rate of the culture, was consistent with the finite birth rate predicted from the population's egg ratio and egg age distribution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47764/1/442_2004_Article_BF00410359.pd

A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains

Offspring size in Daphnia: does it pay to be overweight?

Variation in offspring size and number has been described for a wide range of organisms. In this study I investigated the relationship between resource level of the mother and size of her offspring in the cladoceran Daphnia magna, in order to assess whether offspring produced at different food levels are optimal in size for these food levels. Optimal offspring size was defined as the size of offspring that yields the highest parental fitness (i.e. offspring of optimal size have the highest juvenile fitness per unit maternal effort invested in them). I observed that especially at the higher food levels, daphnids produced offspring that are larger than the computed optimal offspring size at these food levels. I interpret this as a mechanism to avoid starvation of neonates in the case of suddenly deteriorating food conditions