New complexities in the genetics of stuttering: significant sex-specific linkage signals

Stuttering is a speech disorder long recognized to have a genetic component. Recent linkage studies mapped a susceptibility locus for stuttering to chromosome 12 in 46 highly inbred families ascertained in Pakistan. We report here on linkage studies in 100 families of European descent ascertained in the United States, Sweden, and Israel. These families included 252 individuals exhibiting persistent stuttering, 45 individuals classified as recovered from stuttering, and 19 individuals too young to classify. Primary analyses identified moderate evidence for linkage of the broader diagnosis of "ever stuttered" (including both persistent and recovered stuttering) on chromosome 9 (LOD = 2.3 at 60 cM) and of the narrower diagnosis of persistent stuttering on chromosome 15 (LOD = 1.95 at 23 cM). In contrast, sex-specific evidence for linkage on chromosome 7 at 153 cM in the male-only data subset (LOD = 2.99) and on chromosome 21 at 34 cM in the female-only data subset (LOD = 4.5) met genomewide criteria for significance. Secondary analyses revealed a significant increase in the evidence for linkage on chromosome 12, conditional on the evidence for linkage at chromosome 7, with the location of the increased signal congruent with the previously reported signal in families ascertained in Pakistan. In addition, a region on chromosome 2 (193 cM) showed a significant increase in the evidence for linkage conditional on either chromosome 9 (positive) or chromosome 7 (negative); this chromosome 2 region has been implicated elsewhere in studies on autism, with increased evidence for linkage observed when the sample is restricted to those with delayed onset of phrase speech. Our results support the hypothesis that the genetic component to stuttering has significant sex effects.     

血液磁极化疗法对糖尿病兔胰岛功能的影响

目的观察血液磁极化疗法(简称血磁治疗)对糖尿病(DM)的治疗效果和对胰岛功能的影响。方法制备了四氧嘧啶DM兔模型20只,随机分为两组,即DM模型血磁治疗组及DM模型未治疗组,同时设立正常对照组10只,分别测定治疗前后空腹血糖(FPG)、糖化血红蛋白(HbA1c)、胰岛素(INS)及C-肽(C-P),并于观察期结束后处死动物取胰腺组织常规石蜡包埋切片,行HE及Mallory三色法特殊染色观察3组胰岛形态学变化。结果血磁治疗显著降低DM兔的FPG(P<0.001)。DM治疗组INS及C-P水平较治疗前明显升高(P<0.01),与未治疗组相比差异显著(P<0.05)。胰岛病理改变可见治疗组β细胞数量明显多于DM未治疗组,提示血磁疗法具有促进胰岛修复,改善胰岛功能的作用。结论血磁疗法能够促进DM时受损胰岛组织的修复,改善胰岛β细胞分泌功能,降血糖作用明显。     

Nematode and macrofaunal diversity in central Arctic Ocean benthos

Deep-sea diversity studies have revealed intriguing patterns on both local and regional scales, but there is insufficient evidence with which to evaluate these trends in the Arctic Ocean basin. We collected data on the diversity of benthic macrofauna and meiofaunal nematodes along two transects from the shelf margin to the North Pole. Contrary to prevailing paradigms, there was no change in diversity with depth between 1000 and 4273 m. There was a trend, however, toward reduced taxonomic richness for both macrofauna and nematodes with increasing latitude. Regional (β-) diversity differences were not observed for nematodes, but significant contrasts in Bray-Curtis similarity-based community structure of macrofauna were seen between the Eurasian and Amerasian Basins, as well as between the Lomonosov and Mendeleev Ridges. Since fauna within the deep Arctic Ocean appear to represent a single species pool, we suggest that both local (α-) and β-diversity may be determined by ecological processes in the Arctic, and are not the consequence of historical or evolutionary processes. Furthermore, insights gained from studies of benthic-pelagic coupling, known to play a significant role in determining benthic community structure and function at high latitudes, may also be useful in investigations of Arctic biodiversity. This model may be valuable in designing future studies of biodiversity, and for predicting potential impacts of climate change on diversity patterns.     

Obstructive sleep apnea and chronic intermittent hypoxia: a review

Hypoxia is an important topic both physiologically and clinically. Traditionally, physiology research has been focusing on the effect of acute and chronic sustained hypoxia and human adaptive response to high altitude. In the past 20 years, genetic studies by many have expanded our understanding of hypoxia to the molecular level. However, in contrast to our extensive knowledge about acute and chronic sustained hypoxia, we know relatively little about the effect of chronic intermittent hypoxia (CIH). In recent years, CIH has attracted more research attention because of the increasing prevalence of obesity and obstructive sleep apnea (OSA) in the western countries. Clinically, CIH is commonly seen in patients with sleep-disordered breathing including OSA, Cheyne-Stokes respiration and nocturnal hypoventilation. It was estimated that for OSA of at least mild severity prevalence estimates range from 3 to 28% in the general population. OSA is characterized by recurrent upper airway collapse during sleep leading to intermittent nocturnal hypoxia and sleep fragmentation. OSA is associated with significant mortality and morbidity including neurocognitive dysfunction, hypertension, many cardiovascular disorders and metabolic disorders such as diabetes and metabolic syndrome. The intermittent hypoxia in OSA closely mimics what is seen in the ischemia-reperfusion injury. Experimentally, there is no universally accepted definition for CIH. Laboratory protocols vary greatly in duration of hypoxia exposure, numbers of hypoxia episodes per day and the total number of days of exposure. Despite the lack of a uniform definition, recent data suggest that CIH may lead to multiple long-term pathophysiologic consequences similar to what we see in patients with OSA. Recent evidences also demonstrate that there are remarkable differences in the response of the physiologic systems to sustained hypoxia and intermittent hypoxia. This review is aimed to briefly discuss the clinical significance of sleep-disordered breathing and our current understanding of CIH.     

Growth line deposition and variability in growth of two circumpolar bivalves (Serripes groenlandicus, and Clinocardium ciliatum)

Growth patterns of two common circumpolar bivalves, the Greenland cockle (Serripes groenlandicus), and the hairy cockle (Clinocardium ciliatum) have been used in previous studies to reconstruct environmental conditions in the arctic. To date, there has been no direct determination that growth lines in either species are deposited periodically, and there has been no examination of factors affecting growth. We placed calcein-marked individuals of both species on oceanographic moorings in two fjords (Rijpfjord and Kongsfjord) in the Svalbard archipelago for one and two (Kongsfjord only) years. Growth patterns were compared with concurrent in situ temperature and fluorescence data in order to assess environmental controls on growth. Dark growth lines are evident on the outer shell surface and internally in shell cross section in both S. groenlandicus and C. ciliatum, and both species deposited only one line per year, unequivocally confirming that internal lines are deposited annually. Growth line deposition in both species began in late summer to early fall, before the seasonal decline in temperature. There was no difference in growth of S. groenlandicus between the two fjords despite differences in water temperature (3°C), fluorescence (nearly threefold) and the onset and duration of the winter season. C. ciliatum, however, grew approximately 2.8 times faster in the warmer, more food-rich Kongsfjord than in Rijpfjord. Subannual lines were counted in two individuals of each species from each fjord, but deposition of these lines was not clearly related to number of growing days estimated by temperature and fluorescence.     

Hyaluronic acid receptor CD44 deficiency is associated with decreased Cryptococcus neoformans brain infection

Cryptococcus neoformans is a pathogenic yeast that can invade the brain and cause meningoencephalitis. Our previous in vitro studies suggested that the interaction between C. neoformans hyaluronic acid and human brain endothelial CD44 could be the initial step of brain invasion. In this report, we used a CD44 knock-out (KO or CD44(-/-)) mouse model to explore the importance of CD44 in C. neoformans brain invasion. Our results showed that C. neoformans-infected CD44 KO mice survived longer than the infected wild-type mice. Consistent with our in vitro results, the brain and cerebrospinal fluid fungal burden was reduced in CD44-deficient mice. Histopathological studies showed smaller and fewer cystic lesions in the brains of CD44 KO mice. Interestingly, the cystic lesions contained C. neoformans cells embedded within their polysaccharide capsule and were surrounded by host glial cells. We also found that a secondary hyaluronic acid receptor, RHAMM (receptor of hyaluronan-mediated motility), was present in the CD44 KO mice. Importantly, our studies demonstrated an in vivo blocking effect of simvastatin. These results suggest that the CD44 and RHAMM receptors function on membrane lipid rafts during invasion and that simvastatin may have a potential therapeutic role in C. neoformans infections of the brain.