Small marker chromosomes in two patients with segmental aneusomy for proximal 17p

We report a nine-year-old girl (patient 1934) and a five-year-old boy (patient 2170) with small, de novo supernumerary marker chromosomes (SMCs) derived from proximal 17p. The clinical features of patient 1934 include developmental delay, triangular face, prominent forehead, low set ears, dental abnormalities, a high arched palate, long, flexible fingers, and joint laxity. Patient 2170 is affected with developmental delay, oral-motor dyspraxia/verbal apraxia, thick upper and lower lips, bilateral fifth finger clinodactyly, joint laxity and mild hypotonia. G-banded chromosome analysis of patient 1934 revealed mosaicism for a SMC in 72% of peripheral lymphocytes analyzed, whereas analysis of patient 2170 identified a smaller SMC present in 100% of cells analyzed. Fluorescence in situ hybridization (FISH) studies demonstrated that both of the SMCs derived from 17p10-p11.2. Using FISH and array-CGH analysis, the proximal breakpoints mapped within the centromere and the distal breakpoints were both located within the Smith-Magenis syndrome (SMS) common deletion region. We compare the clinical characteristics of our patients with those previously reported to have either SMC including 17p or duplications of proximal 17p in an effort to further delineate the phenotype of trisomy 17p10-p11.2 and to elucidate genotype-phenotype correlations.     

迁移的鼻咽癌细胞容积激活性氯电流

用膜片钳技术研究了Transwell小室趋化迁移后的鼻咽癌CNE-2Z细胞容积激活性CT电流。47％低渗刺激迁移后的CNE-2Z细胞诱发容积激活性氯电流,与未迁移细胞相比,其特性以及其对氯通道阻断剂的敏感性发生明显的变化,此电流的密度明显高于未迁移细胞,而且该电流几乎完全被氯通道阻断剂adenosine-5'-triphosphate(ATP,10 mmol/L)、5-nitro-2-3-phenylpropylamino benzoic acid(NPPB,100μmol/L)和他莫昔芬(30μmol/L)抑制,其中NPPB和他莫昔芬对迁移细胞的抑制作用明显强于未迁移细胞。迁移后的CNE-2Z细胞容积激活性氯通道对阴离子的通透性为:Br>Cl>I>葡萄糖酸,与未迁移细胞(I>Br>Cl>葡萄糖酸)不同。结果提示,容积激活性氯通道可能参与CNE-2Z细胞的迁移过程。     

ATP激活鼻咽癌细胞氯电流并减小细胞容积

采用全细胞膜片钳技术和细胞容积测量技术,在低分化鼻咽癌细胞株CNE-2Z上观察ATP 诱导的Cl- 电流的特性及其对细胞容积的影响。细胞外微摩尔水平的ATP 以剂量依赖性的方式激活一个具有弱外向整流特性,没有时间依赖性失活的电流,此电流的反转电位 [(-0.05 ± 0.03) mV]接近Cl- 的平衡电位(-0.9 mV)。用葡萄糖酸置换细胞外液Cl- 后, ATP 激活的电流明显减小并且反转电位发生改变。氯通道抑制剂NPPB (200 μmol/L)可以抑制这一电流 [(81.03 ± 9.3)%] 。此电流亦可被嘌呤受体(P2Y) 拮抗剂反应蓝 2 抑制 [(67.39 ± 5.06)%]。50 μmol/L 的 ATP 使在等渗状态下的细胞容积缩小, 替代和耗竭细胞外、内的Cl- 后, ATP 的这一作用消失。这些结果提示细胞外微摩尔水平的 ATP 可通过兴奋 P2Y 受体激活氯通道而产生与细胞容积调节相关的Cl- 电流。     

Inferring ethanol tolerance of Saccharomyces and non-Saccharomyces yeasts by progressive inactivation

The kinetics of cell inactivation in the presence of ethanol at 20, 22.5% and 25% (v/v), was measured by progressive sampling and viable counting, and used as an inference of the ethanol resistance status of five non-Saccharomyces strains and one strain of Saccharomyces cerevisiae. The capacity of standard inocula of the same strains to establish growth at increasing initial ethanol concentrations was employed as a comparison. The effect of various different pre-culture conditions on the ethanol resistance of the 6 strains was analysed by the cell inactivation method and by the cell growth method. Exposing cells to 25% (v/v) ethanol for 4 min enabled the differentiation of the yeasts in terms of their resistance to ethanol. The results suggest that the two methods are generally concordant and that the cell inactivation method can, thus, be used to infer ethanol resistance of yeast strains.     

Skeletons, noise and population growth: the end of an old debate?

Population dynamics models remain largely deterministic, although the presence of random fluctuations in nature is well recognized. This deterministic approach is based on the implicit assumption that systems can be separated into a deterministic part that captures the essential features of the system and a random part that can be neglected. But is it possible, in general, to understand population dynamics without the explicit consideration of random fluctuations? Here, we suggest perhaps not, and argue that the dynamics of many systems are a result of interactions between the deterministic nonlinear skeleton and noise.     

A model of inflammatory arthritis highlights a role for oncostatin M in pro-inflammatory cytokine-induced bone destruction via RANK/RANKL

Oncostatin M is a pro-inflammatory cytokine previously shown to promote marked cartilage destruction both in vitro and in vivo when in combination with IL-1 or tumour necrosis factor alpha. However, the in vivo effects of these potent cytokine combinations on bone catabolism are unknown. Using adenoviral gene transfer, we have overexpressed oncostatin M in combination with either IL-1 or tumour necrosis factor alpha intra-articularly in the knees of C57BL/6 mice. Both of these combinations induced marked bone damage and markedly increased tartrate-resistant acid phosphatase-positive multinucleate cell staining in the synovium and at the front of bone erosions. Furthermore, there was increased expression of RANK and its ligand RANKL in the inflammatory cells, in inflamed synovium and in articular cartilage of knee joints treated with the cytokine combinations compared with expression in joints treated with the cytokines alone or the control. This model of inflammatory arthritis demonstrates that, in vivo, oncostatin M in combination with either IL-1 or tumour necrosis factor alpha represents cytokine combinations that promote bone destruction. The model also provides further evidence that increased osteoclast-like, tartrate-resistant acid phosphatase-positive staining multinucleate cells and upregulation of RANK/RANKL in joint tissues are key factors in pathological bone destruction.     

Optimal assessment of multiple cues

In a wide range of contexts from mate choice to foraging, animals are required to discriminate between alternative options on the basis of multiple cues. How should they best assess such complex multicomponent stimuli? Here, we construct a model to investigate this problem, focusing on a simple case where a ''chooser'' faces a discrimination task involving two cues. These cues vary in their accuracy and in how costly they are to assess. As an example, we consider a mate-choice situation where females choose between males of differing quality. Our model predicts the following: (i) females should become less choosy as the cost of finding new males increases; (ii) females should prioritize cues differently depending on how choosy they are; (iii) females may sometimes prioritize less accurate cues; and (iv) which cues are most important depends on the abundance of desirable mates. These predictions are testable in mate-choice experiments where the costs of choice can be manipulated. Our findings are applicable to other discrimination tasks besides mate choice, for example a predator''s choice between palatable and unpalatable prey, or an altruist''s choice between kin and non-kin.     

Habitat conversion and global avian biodiversity loss

The magnitude of the impacts of human activities on global biodiversity has been documented at several organizational levels. However, although there have been numerous studies of the effects of local-scale changes in land use (e.g. logging) on the abundance of groups of organisms, broader continental or global-scale analyses addressing the same basic issues remain largely wanting. None the less, changing patterns of land use, associated with the appropriation of increasing proportions of net primary productivity by the human population, seem likely not simply to have reduced the diversity of life, but also to have reduced the carrying capacity of the environment in terms of the numbers of other organisms that it can sustain. Here, we estimate the size of the existing global breeding bird population, and then make a first approximation as to how much this has been modified as a consequence of land-use changes wrought by human activities. Summing numbers across different land-use classes gives a best current estimate of a global population of less than 100 billion breeding bird individuals. Applying the same methodology to estimates of original land-use distributions suggests that conservatively this may represent a loss of between a fifth and a quarter of pre-agricultural bird numbers. This loss is shared across a range of temperate and tropical land-use types.