Increased noise sensitivity and altered inner ear MENA distribution in VASP−/− mice

Vasodilator-stimulated phosphoprotein (VASP) and mammalian-enabled protein (MENA) share similar cellular localisation and functions (signal transduction pathways, regulation of actin cytoskeleton dynamics). Functional substitution and compensation among Ena/VASP proteins have been proposed as the reason for the absence of major morphological and functional deficits in VASP–/– mice. The aim of this study was to investigate VASP expression in the mouse cochlea, to analyse cochlear function in VASP–/– mice compared with wildtype mice, and to analyse cochlear MENA distribution taking into account that MENA protein might compensate VASP loss in the cochlea of VASP–/– mice. We confirmed specific VASP expression in the pillar cells of the mice organ of Corti as previously reported for rat cochlea. By analysing the hearing function in VASP–/– mice, we found no differences in auditory brainstem responses and distortion product otoacoustic emissions from those of wildtype mice but evidence for an increased noise sensitivity at lower frequencies. When MENA protein levels in cochlea tissue were tested in mutant and wildtype mice by Western blot analysis, no significant differences were found, as was also seen with regard to MENA mRNA levels in laser-microdissected single pillar cells. Most surprisingly, however, MENA protein was absent in pillar cells of VASP–/– mice, whereas it was detected in other cochlear cells. The finding of a cell-specific, and not organ-specific, redundancy of MENA protein expression noted for the first time in VASP–/– mice is proposed as the reason for the observed distinct cochlear phenotype.     

Cathepsin B mRNA and protein expression following contusion spinal cord injury in rats

We provide the first data that cathepsin B (Cath B), a lysosomal cysteine protease, is up-regulated following contusion-spinal cord injury (SCI). Following T12 laminectomy and moderate contusion, Cath B mRNA and protein expression profiles were examined from 2 to 168 h post-injury in rats using real-time PCR and immunoblots, respectively. Contusion injury significantly increased [mRNA]Cath B in the injury site and adjacent segments over sham injury levels. While the largest [mRNA]Cath B induction (20-fold over naive) was seen in the injury site, the caudal segment routinely yielded [mRNA]Cath B levels greater than 10-fold over naive. Interestingly, sham injury animals also experienced mRNA induction at several time points at the injury site and in segments rostral and caudal to the injury site. Contusion injury also significantly elevated levels of Cath B proenzyme protein (37 kDa) over sham injury in the injury site (48, 72 and 168 h post-injury). Furthermore, significant protein increases of single and double chain Cath B (both active forms) occurred at the injury site at 72 and 168 h post-injury. Similar significant increases in Cath B protein levels were seen in areas adjacent to the injury site. The induction of Cath B mRNA and protein expression following contusion injury is previously undescribed and suggests that Cath B may potentially be involved in the secondary injury cascade, perhaps for as long as 1 week post-injury.     

4-Hydroxynonenal induces oxidative stress and death of cultured spinal cord neurons

Primary spinal cord trauma can trigger a cascade of secondary processes leading to delayed and amplified injury to spinal cord neurons. Release of fatty acids, in particular arachidonic acid, from cell membranes is believed to contribute significantly to these events. Mechanisms of fatty acid-induced injury to spinal cord neurons may include lipid peroxidation. One of the major biologically active products of arachidonic acid peroxidation is 4-hydroxynonenal (HNE). The levels of HNE-protein conjugates in cultured spinal cord neurons increased in a dose-dependent manner after a 24-h exposure to arachidonic acid. To study cellular effects of HNE, spinal cord neurons were treated with different doses of HNE, and cellular oxidative stress, intracellular calcium, and cell viability were determined. A 3-h exposure to 10 microM HNE caused approximately 80% increase in oxidative stress and 30% elevation of intracellular calcium. Exposure of spinal cord neurons to HNE caused a dramatic loss of cellular viability, indicated by a dose-dependent decrease in MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-s ulfophenyl)- 2H-tetrazolium, inner salt] conversion. The cytotoxic effect of HNE was diminished by pretreating neurons with ebselen or N-acetylcysteine. These data support the hypothesis that formation of HNE may be responsible, at least in part, for the cytotoxic effects of membrane-released arachidonic acid to spinal cord neurons.     

Unraveling Silence: Violence,Memory and the Limits of Anthropology’s Craft<Superscript>1</Superscript>

What are the ethical dilemmas that conducting anthropological on memory in South Africa poses to the student of violence? In the specific context of “victim support groups” in post-1994 South Africa, one of the most problematic issues relates to the interactions between “trauma experts” and “victims.” In the view of many survivors, the violence of voicelessness, an issue to which there is a particular sensitivity in the country, is re-inscribed in their life through the specific intervention of social scientists. One of the effects of this interventions, which determines the limits and possibilities of any research on memory as it connects to violence, is a widespread reaction against experts, whose work, the production and dissemination of knowledge about trauma on the basis of other people’s experiences, is often perceived by survivors as being part of a broader economy of subtraction where their “voices” have become commodities in a transnational network of prestige.     

Stress responses and innate immunity: aging as a contributory factor

Evolutionary pressure has selected individuals with traits that allow them to survive to reproduction, without consideration of the consequences for the post-child rearing years and old age. In the 21st century, society is populated increasingly by the elderly and with the falling birth rate and improved health care this trend is set to continue for the foreseeable future. To minimize the potential burden on health services one would hope that 'growing old gracefully' should also mean 'growing old healthily'. However, for too many the aging process is accompanied by increasing physical and mental frailty producing an elevated risk of physical and psychological stress in old age. Stress is a potent modulator of immune function, which in youth can be compensated for by the presence of an optimal immune response. In the elderly the immune response is blunted as a result of the decline in several components of the immune system (immune senescence) and a shifting to a chronic pro-inflammatory status (the so-called 'inflamm-aging' effect). We discuss here what is known of the effects of both stress and aging upon the innate immune system, focusing in particular upon the age-related alterations in the hypopituitary-adrenal axis. We propose a double hit model for age and stress in which the age-related increase in the cortisol/sulphated dehydroepiandrosterone ratio synergizes with elevated cortisol during stress to reduce immunity in the elderly significantly.     

损伤控制外科在严重胸外伤为主的全身多发伤救治中的应用

目的:探讨损伤控制外科(DCS)在严重胸外伤为主的全身多发伤救治中应用的临床效果。方法:2010年1月至2012年6月收治的57例患者采用早期全面治疗(ETC组),2012年7月至2013年12月收治的57例患者采用DCS理论救治(DCS组)。比较两组相关生理指标恢复情况及并发症的发生情况。结果:与ETC组比较,DCS组乳酸清除时间、体温恢复时间、PT和APTT恢复时间、住院时间、ICU治疗时间明显缩短,出血量明显减少(P0.05);DCS组腹腔感染、ARDS、应激性溃疡的发生率及死亡率均较ETC组明显降低(P0.05)。结论:严重胸外伤为主的全身多发伤救治中应用DCS理论可明显改善患者生理指标恢复,减少并发症,提高救治成功率。     

The effects of α-lipoic acid on immature rats with traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality during childhood. TBI enhances formation of reactive oxygen species that cause neuron damage and apoptosis. α-Lipoic acid (LA) is a free radical scavenger and biological antioxidant. We investigated the effects of LA treatment on the parietal and prefrontal cortex, and on the hippocampal regions of the brain in 7-day-old rat pups that had been subjected to contusion injury. Forty-two male rats were divided randomly into a control group, a TBI group and a TBI + LA treated group. LA was administered 30 min after TBI through an intragastric tube once daily for 2 days. Forty-eight hours after TBI, the animals were sacrificed and tissues were examined for apoptosis and density of neurons. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and active caspase-3 immunostaining were used to detect apoptosis. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels also were measured. Histological evaluation showed that LA treatment significantly reduced TBI-induced neuronal death in the hippocampus, prefrontal and parietal cortex; TUNEL- and caspase-3-positive cells also were decreased in the same regions. In addition, LA administration increased GPx and SOD activity in the prefrontal cortex. It appears that LA may be beneficial for TBI in rats.     

基于三维人脸模型及人工测量数据分析现代中国人群面部表型的性别差异

传统体质人类学研究中的样本采集方法是手工测量以及肉眼观察,采集过程中会存在较大的主观性,易产生误差,同时在采集大样本时费时费力。近年来,三维摄像系统被越来越多的应用于人脸分析,其优势是快速高效和准确,并且涵盖了传统测量方法无法精确获取的表型特征信息,可以更加细化地分析人脸表型特征和特征之间的相互关系。本研究探索性地基于三维人脸模型图像,利用曲率和邻域信息的点筛查方法定位了面部的一些关键测量点,建立一套简单、有效、准确率较高的三维人脸模型图像关键点定位方法,能较准确地定位98%以上的眼内角点和鼻尖点,并在此基础上确定了鼻根点、鼻下点、左右鼻翼点和鼻翼外侧最低点等其他面部关键点。并且还提出了在三维人脸模型图像基础上量化部分面部观察类表型特征,如鼻侧深度、鼻根高度、面部扁平度等,尝试性地将这些观察类性状转化为能够测量的性状,建立了一套可以计算的描述方法,具有一定的创新性。本研究还结合三维人脸模型提取数据和人工测量数据,探讨了现代中国人群(以江淮汉族为例)面部表型特征的性别差异,发现大多数面部表型特征在现代中国人群中都存在明显的男女性别差异,鼻侧深度、鼻根高度、面部扁平度的性别差异最为显著,其Z检验的p值均小于0.01。结果显示男性的鼻部整体比女性更大更前凸,而女性的面部更为扁平。     

CB1 receptors in corticotropin-releasing factor neurons selectively control the acoustic startle response in male mice

The endocannabinoid system is an important regulator of the hormonal and behavioral stress responses, which critically involve corticotropin-releasing factor (CRF) and its receptors. While it has been shown that CRF and the cannabinoid type 1 (CB1) receptor are co-localized in several brain regions, the physiological relevance of this co-expression remains unclear. Using double in situ hybridization, we confirmed co-localization in the piriform cortex, the lateral hypothalamic area, the paraventricular nucleus, and the Barrington's nucleus, albeit at low levels. To study the behavioral and physiological implications of this co-expression, we generated a conditional knockout mouse line that selectively lacks the expression of CB1 receptors in CRF neurons. We found no effects on fear and anxiety-related behaviors under basal conditions nor after a traumatic experience. Additionally, plasma corticosterone levels were unaffected at baseline and after restraint stress. Only acoustic startle responses were significantly enhanced in male, but not female, knockout mice. Taken together, the consequences of depleting CB1 in CRF-positive neurons caused a confined hyperarousal phenotype in a sex-dependent manner. The current results suggest that the important interplay between the central endocannabinoid and CRF systems in regulating the organism's stress response is predominantly taking place at the level of CRF receptor-expressing neurons.