Immunocytochemical approach to the structure of human blood group B and H glycoconjugate antigens in the three days old rat cochlea

The possible structure of human blood-group antigens, as found in cochlear hair cells of 3-day-old rats, is suggested. Data were obtained from immunocytochemical studies using 77 antibodies against the major human blood group antigens of the ABO, H, I and Lewis genetic systems. Neither the anti-A-related nor the anti-Lewis-related antibodies showed any positive immunoreaction on hair cells. In contrast, anti-B, anti-AB and anti-H antibodies displayed specific positive immunoreactive patterns on the hair cells. The results suggest that, in immature hair cells, two main glycoconjugate structures of the lactoseries are present: H type 2 antigen, which is the precursor of the B type 2 antigen, and the B type 2 antigen itself. Similar H and B carbohydrate structures have been reported in rat olfactory receptors. The type 2 glycoconjugates carrying these H and B antigens of auditive and olfactory receptors are resistant to fixation and paraffin embedding, suggesting that they might be glycoproteins. These auditive and olfactory H and B antigens must be different from the B-related antigens that are expressed by pseudo-unipolar neurons of rat posterior root ganglia, that are built from type 4 core chains, and that are destroyed by routine paraffin embedding procedures.     

Hyposensitive canopy conductance renders ecosystems vulnerable to meteorological droughts

Increased meteorological drought intensity with rising atmospheric demand for water (hereafter vapor pressure deficit [VPD]) increases the risk of tree mortality and ecosystem dysfunction worldwide. Ecosystem-scale water-use strategy is increasingly recognized as a key factor in regulating drought-related ecosystem responses. However, the link between water-use strategy and ecosystem vulnerability to meteorological droughts is poorly established. Using the global flux observations, historic hydroclimatic data, remote-sensing products, and plant functional-trait archive, we identified potentially vulnerable ecosystems, examining how ecosystem water-use strategy, quantified by the percentage bias (δ) of the empirical canopy conductance sensitivity to VPD relative to the theoretical value, mediated ecosystem responses to droughts. We found that prevailing soil water availability substantially impacted δ in dryland regions where ecosystems with insufficient soil moisture usually showed conservative water-use strategy, while ecosystems in humid regions exhibited more pronounced climatic adaptability. Hyposensitive and hypersensitive ecosystems, classified based on δ falling below or above the theoretical sensitivity, respectively, achieved similar net ecosystem productivity during droughts, employing different structural and functional strategies. However, hyposensitive ecosystems, risking their hydraulic system with a permissive water-use strategy, were unable to recover from droughts as quickly as hypersensitive ones. Our findings highlight that processed-based models predicting current functions and future performance of vegetation should account for the greater vulnerability of hyposensitive ecosystems to intensifying atmospheric and soil droughts.     

山医群体近交系中国地鼠(Cricetulus griseus)的研究——Ⅲ.生物学特性

山医群体近交系中国地鼠的红细胞、白细胞、网织红细胞、血红蛋白及血清蛋白量均与人类相近。血小板数高于人类,但低于小鼠。嗜中性与淋巴细胞的比值与人类相反而与小鼠近似。血清尿素氮及谷丙转氨酶高于人类生理值,低于SD大鼠。心率为658±102次/min,呼吸率20±30次/min。心电图除T波低平外,其余与人类相近。颈动脉血压为13.47±1.01/12.48±1.09kPa。染色体数为2n=22。以上各项在近交系地鼠和野生地鼠间未见明显差异。     

高寒草甸植物群落功能多样性对不同生长期干旱的响应机制

植物对干旱胁迫的响应表现为各功能性状的差异化表达。全球气候变化下,青藏高原地区降水格局发生改变,高寒草甸群落功能性状及功能多样性在不同生长期干旱事件下的响应机制对加深高寒草甸适应气候变化认知具有重要意义。以藏北高寒草甸为研究对象,设置截雨棚模拟生长季前期（ED）、中期（MD）和非生长季时期（ND）干旱事件,通过观测群落物种功能性状,分析高寒草甸群落功能多样性对不同生长期干旱的响应机制。结果表明：（1）叶片功能性状对干旱存在差异响应,表现为叶片小而厚且寿命长,同化速率降低,并受氮元素限制加剧;（2）生长季前期干旱对高寒草甸群落功能性状的影响最强,生长季中期干旱次之,非生长季干旱的影响最弱;（3）生长季干旱处理显著改变了群落的功能多样性,ED处理下功能分散度指数（FDiv）和功能分异度指数（FDis）显著降低（P<0.05）,而Rao二次熵指数（RaoQ）显著升高（P<0.05）,MD处理下功能均匀度指数（FEve）显著降低（P<0.05）;（4）相关性分析得出,群落功能性状与功能多样性对干旱的响应之间存在着联系。本研究发现高寒草甸植物功能性状与群落功能多样性对生长季前期和中期干旱存在差异化响应,指示着高寒草甸植物群落在响应不同时期干旱时可能采取不同的生存策略,即对生长季前期干旱采用耐旱策略、对生长季中期干旱采用避旱策略。探讨了高寒草甸植物群落功能多样性对不同生长时期干旱胁迫的响应机制,为预测未来季节性干旱事件对青藏高原高寒草甸植物功能性状、群落特征和功能多样性的影响提供科学依据。     

Human urinary and blood toxicokinetics of beryllium after accidental exposure

PurposeBeryllium is known to have adverse health effects and is classified as carcinogenic to humans. However, data on systemic beryllium exposure in humans are rare and especially human toxicokinetics are largely uncharted. As such, the first reported multi-annual course of blood and urine concentrations after a high exposure scenario provides important new insights.MethodsFor a medical follow-up biomonitoring samples were collected for 56 months from a male subject after an accidental and multi-faceted high exposure. Sampling started on day 2 post-exposure for urine and day 147 for blood. The samples were analyzed by inductively coupled mass spectrometry (ICP-MS) and plotted longitudinally as a function of time. Terminal half-lives were calculated assuming a first-order elimination process.Main findingsBoth matrices showed highly increased initial concentrations (about 100-fold), despite the 147-day delay in blood sampling, and a marked decline over time. In urine, a two-phase excretion process was suspected based on the longitudinal data. Calculations gave terminal half-lives of 117.5 days and 666.5 days for phases 1 and 2, respectively. Blood kinetics called for a terminal half-life of 103.5 days. Elimination kinetics in blood and urine were comparable, simultaneously gathered samples showed an excellent correlation (R² = 0.985).Principal conclusionsThe long-term follow-up after a high initial exposure to beryllium provides the first detailed insights into the elimination course of systemically available beryllium in humans. Conform kinetics of beryllium in urine and blood and the strong correlation between both parameters indicate high data validity and support the good representation of the current systemically available beryllium by urine and blood concentration in humans. The relatively long terminal half-lives in both matrices suggest a possible accumulation in humans in case of repeated exposures.     

Exposure of preterm neonates to toxic metals during their stay in the Neonatal Intensive Care Unit and its impact on neurodevelopment at 2 months of age

BackgroundPremature neonates might be exposed to toxic metals during their stay in the neonatal intensive care unit (NICU), which could adversely affect neurodevelopment; however, limited evidence is available. The present study was therefore designed to assess the exposure to mercury, lead, cadmium, arsenic, and manganese of preterm neonates who received total parenteral nutrition (TPN) and/or red blood cell (RBC) transfusions during their NICU stay and the risk of neurodevelopment delay at the age of 2 months.MethodsWe recruited 33 preterm neonates who required TPN during their NICU admission. Blood samples were collected for metal analysis at two different time points (admission and before discharge). Metals in the daily TPN received by preterm neonates were analyzed. Neurodevelopment was assessed using the Ages and Stages Questionnaire Edition 3 (ASQ-3).ResultsAll samples of TPN had metal contamination: 96% exceeded the critical arsenic limit (0.3 μg/kg body weight/day); daily manganese intake from TPN for preterm neonates exceeded the recommended dose (1 µg/kg body weight) as it was added intentionally to TPN solutions, raising potential safety concerns. All samples of RBC transfusions exceeded the estimated intravenous reference dose for lead (0.19 µg/kg body weight). Levels of mercury, lead and manganese in preterm neonates at discharge decreased 0.867 µg/L (95% CI, 0.76, 0.988), 0.831 (95%CI, 0.779, 0.886) and 0.847 µg/L (95% CI, 0.775, 0.926), respectively. A decrease in ASQ-3-problem solving scores was associated with higher levels of blood lead in preterm neonates taken at admission (ß = −0.405, 95%CI = −0.655, −0.014), and with plasma manganese (ß = −0.562, 95%CI = −0.995, −0.172). We also observed an association between decreased personal social domain scores with higher blood lead levels of preterm neonates before discharge (ß = −0.537, 95%CI = −0.905, −0.045).ConclusionOur findings provide evidence to suggest negative impacts on the neurodevelopment at 2 months of preterm infants exposed to certain metals, possibly related to TPN intake and/or blood transfusions received during their NICU stay. Preterm neonates may be exposed to levels of metals in utero.     

The role of non-natural foods in the nutritional strategies of monkeys in a human-modified mosaic landscape

Many tropical animals inhabit mosaic landscapes including human-modified habitat. In such landscapes, animals commonly adjust feeding behavior, and may incorporate non-natural foods. These behavioral shifts can influence consumers' nutritional states, with implications for population persistence. However, few studies have addressed the nutritional role of non-natural food. We examined nutritional ecology of wild blue monkeys to understand how dietary habits related to non-natural foods might support population persistence in a mosaic landscape. We documented prevalence and nutritional composition of non-natural foods in monkey diets to assess how habitat use influenced their consumption, and their contribution to nutritional strategies. While most energy and macronutrients came from natural foods, subjects focused non-natural feeding activity on five exotic plants, and averaged about a third of daily calories from non-natural foods. Most non-natural food calories came from non-structural carbohydrates and least from protein. Consumption of non-natural foods related to time in human-modified habitats, which two groups used non-randomly. Non-natural and natural foods were similar in nutrients, and the amount of non-natural food consumed drove variation in nutritional strategy. When more daily calories came from non-natural foods, females consumed a higher ratio of non-protein energy to protein (NPE:P). Females also prioritized protein while allowing NPE:P to vary, increasing NPE while capitalizing on non-natural foods. Overall, these tropical mammals achieved a similar nutrient balance regardless of their intake of non-natural foods. Forest and forest-adjacent areas with non-natural vegetation may provide adequate nutrient access for consumers, and thus contribute to wildlife conservation in mosaic tropical landscapes.     

Circadian Rhythm of Cardiac Output, Peripheral Vascular Resistance, and Related Variables by a Beat-to-Beat Monitoring

This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomano-metric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus.     

靶向蛋白质泛素修饰及降解在前列腺癌治疗中的机遇与挑战

前列腺癌是中国发病率增长最快的男性肿瘤,抗雄激素治疗耐药是导致前列腺癌患者预后差的主要原因。因此,解决耐药性难题是前列腺癌转化研究的关键问题。哺乳动物细胞利用泛素-蛋白酶体系统实现蛋白质的靶向降解。因此,前列腺癌中关键的癌基因如雄激素受体（AR）的上游泛素化调控因子（如去泛素化酶）是潜在的治疗靶点。然而,这些酶具有较广的底物谱系,存在脱靶的可能性。近来,基于泛素-蛋白酶体系统开发的蛋白质降解靶向嵌合体（proteolysis-targeting chimeras,PROTAC）技术是最具前景和革命性的新型抗癌药物研发技术,能够利用特定E3泛素连接酶对靶蛋白进行降解而不影响其他底物。与传统小分子抑制剂相比,PROTAC分子在克服耐药性以及针对不可成药的靶点方面拥有巨大优势。目前,针对AR的PROTAC降解剂已在II期临床取得了成功,靶向蛋白质泛素化及降解途径的新技术将有望为前列腺癌的临床治疗带来新的突破。