Slow and fast fiber isoform gene expression is systematically altered in skeletal muscle of the Sox6 mutant, p100H.

We have previously demonstrated that p100H mutant mice, which lack a functional Sox6 gene, exhibit skeletal and cardiac muscle degeneration and develop cardiac conduction abnormalities soon after birth. To understand the role of Sox6 in skeletal muscle development, we identified muscle-specific genes differentially expressed between wild-type and p100H mutant skeletal muscles and investigated their temporal expression in the mutant muscle. We found that, in the mutant skeletal muscle, slow fiber and cardiac isoform genes are expressed at significantly higher levels, whereas fast fiber isoform genes are expressed at significantly lower levels than wild-type. Onset of this aberrant fiber type-specific gene expression in the mutant coincides with the beginning of the secondary myotube formation, at embryonic day 15-16 in mice. Together with our earlier report, demonstrating early postnatal muscle defects in the Sox6 null-p100H mutant, the present results suggest that Sox6 likely plays an important role in muscle development.     

A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4–S5 linker in fast inactivation

Missense mutations in the human skeletal muscle Na⁺ channel α subunit (hSkM1) are responsible for a number of muscle excitability disorders. Among them, paramyotonia congenita (PC) is characterized by episodes of muscle stiffness induced by cold and aggravated by exercise. We have identified a new PC-associated mutation, which substitutes aspartic acid for a conserved alanine in the S4–S5 linker of domain III (A1152D). This residue is of particular interest since its homologue in the rat brain type II Na⁺ channel has been suggested as an essential receptor site for the fast inactivation particle. To identify the biophysical changes induced by the A1152D mutation, we stably expressed hSkM1 mutant or wild-type (WT) channels in HEK293 (human embryonic kidney) cells, and recorded whole-cell Na⁺ currents with the patch-clamp technique. Experiments were performed both at 21 and 11°C to better understand the sensitivity to cold of paramyotonia. The A1152D mutation disrupted channel fast inactivation. In comparison to the WT, mutant channels inactivated with slower kinetics and displayed a 5 mV depolarizing shift in the voltage dependence of the steady-state. The other noticeable defect of A1152D mutant channels was an accelerated rate of deactivation from the inactivated state. Decreasing temperature by 10°C amplified the differences in channel gating kinetics between mutant and WT, and unveiled differences in both the sustained current and channel deactivation from the open state. Overall, cold-exacerbated mutant defects may result in a sufficient excess of Na⁺ influx to produce repetitive firing and myotonia. In the light of previous reports, our data point to functional as well as phenotypic differences between mutations of conserved S4–S5 residues in domains II and III of the human skeletal muscle Na⁺ channel.     

Identification of neurons with acetylcholinesterase and NADPH-diaphorase activities in the centrifugal visual system of the chick

The isthmo-optic nuclei (ION) and ectopic neurons, which constitute the centrifugal visual system (CVS), are thought to be cholinoceptive and nitrergic. However, it is not clear which neurons express these markers, namely the ones that project to the retina rather than in neurons that only participate in a local circuit. Therefore, to characterize the neurochemical patterns of the centrifugal visual system in the post-hatched chick, retinopetal cells of the isthmo-optic nuclei and the ectopic region were identified via immunolabeling for cholera toxin, a neuronal tracer, which has been injected in the ocular globe. Then, double labeled with acetylcholinesterase histochemistry to reveal cholinergic synapses, or NADPH-diaphorase histochemistry as a nitrergic marker. Briefly, acetylcholinesterase activity was present mainly in cholera toxin labeled cell bodies of the isthmo-optic nucleus and the ectopic region indicating that retinal projecting neurons of centrifugal visual system comprise a cholinoceptive pathway. On the other hand, NADPH-diaphorase histochemistry was present in the neuropile and sparse cell bodies inside of the isthmo-optic nucleus and in ectopic neurons which were not cholera toxin positive suggesting their role in an intrinsic circuit of the centrifugal visual system. These data support the idea that these two neurochemical systems are present in distinct neuronal populations in the centrifugal visual system.     

Antagonism of the discriminative effects of ethylketazocine,cyclazocine, and nalorphine in macaques

dl-Ethylketazocine (EKC, 0.01 mg/kg) and saline were established as discriminative stimuli for food-maintained responding in macaque monkeys. Thirty consecutive presses on a right or left lever were reinforced with food, contingent on whether EKC or saline were administered before the session. For tests of antagonism, naltrexone, or UM 979 [(l)-5,9-alpha-dimethyl-2-(3-furylmethyl)-2-hydroxy-6,7-benzomorphan] was administered concomitantly with EKC,dl-cyclazocine, or nalorphine. Both antagonists blocked completely the EKC discriminative stimulus. The antagonism of the stimulus and rate-altering effects of EKC was surmountable, with considerable intersubject variability in the magnitude of the EKC dose increase required to overcome the blockade. Cyclazocine and nalophine, mixed agonist-antagonist opioids that share stimulus properties with EKC, were also susceptible to antagonism. Naltrexone antagonized completely the EKC stimulus effects of nalorphine; naltrexone and UM 979 antagonized completely the EKC stimulus effects of cyclazocine. Naltrexone antagonism of the cyclazocine stimulus was not surmountable, due to a lack of antagonism of the rate-decreasing effects of high cyclazocine doses.     

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results

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Barriers and Facilitators to Participation in Health Screening: an Umbrella Review Across Conditions

Prevention Science - Screening is an essential prevention practice for a number of health conditions. However, screening coverage remains generally low. Studies that investigate determinants of...     

High Prevalence of Low Birth Weight Babies Born to Pregnant Women Referred to a District Hospital in Rural Zambia

Maternal and Child Health Journal - Low birthweight (LBW) is a significant public health problem in sub-Saharan Africa and LBW in rural Zambia is high. Our study explored the prevalence of LBW for...     

Barriers and Facilitators to Effective Implementation of the NAMWEZA Intervention in Dar es Salaam,Tanzania

Prevention Science - The NAMWEZA intervention was implemented, using a ten-session group format, to build skills targeting psychosocial vulnerabilities and enhancing HIV prevention among people...     

In Vivo Observation of Cutaneous Larva Migrans by Fluorescence-Advanced Videodermatoscopy

Fluorescence-advanced videodermatoscopy is not a widespread diagnostic technique. Its application in dermatology can facilitate the diagnosis of diseases such as cutaneous larva migrans by enabling us to recognize the precise position of larva in vivo on the skin. Using this noninvasive technique, we detected a case of cutaneous larva migrans in a patient.