Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.     

MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity

Following homozygosity mapping in a single kindred, we identified nonsense and missense mutations in MYO5B, encoding type Vb myosin motor protein, in individuals with microvillus inclusion disease (MVID). MVID is characterized by lack of microvilli on the surface of enterocytes and occurrence of intracellular vacuolar structures containing microvilli. In addition, mislocalization of transferrin receptor in MVID enterocytes suggests that MYO5B deficiency causes defective trafficking of apical and basolateral proteins in MVID.     

季风与大气环流系统

人类有气象仪器记录的历史太短, 不足以捕捉气候系统全部的变率, 更难以用来预测未来数十年到数百年的气候变化. 重建过去气候变化的历史、理解其机制和过程可以在很大程度上弥补上述不足. 在气候系统中, 由于季风的演化与变率对人类经济、文化和生活节奏的许多方面均有重要影响, 其研究工作对社会的重要性也日益增加. 亚洲季风受欧亚大陆和印度洋-太平洋之间海陆热力差异及青藏高原的强烈影响, 是气候系统非常重要的一个组成部分. 从气候学上讲, 季风区是大气对流活动最强烈的地区, 与热带辐合带密切相关, 对全球大气的热量和水汽传递起着非常重要的作用[1]. 通过地质记录来揭示季风在地质历史时期的变化过程和机制, 对更好地理解季风的变化规律、预测其未来趋势至关重要.     

The balance between immunity and tolerance: The role of Langerhans cells

Langerhans cells are immature skin-homing dendritic cells that furnish the epidermis with an immune surveillance system, and translate information between the internal and external milieu. Dendritic cells, in particular Langerhans cells, are gaining prominence as one of the potential principal players orchestrating the decision between immunity and tolerance. Langerhans cells capture aberrant self-antigen and pathogen-derived antigen for display to the efferent immune response. Recent evidence suggests redundancy in the antigen-presenting function of Langerhans cells, with dermal dendritic subsets capable of fulfilling an analogous role. There is mounting evidence that Langerhans cells can cross-prime T cells to recognize antigens. Langerhans cells are proposed to stimulate T regulatory cells, and are implicated in the pathogenesis of cutaneous T cell lymphoma.The phenotype of Langerhans cells, which may be tolerogenic or immunogenic, appears to depend on their state of maturity, inciting immunogen and cytokine environment, offering the potential for manipulation in immunotherapy. Received 6 August 2008; received after revision 18 September 2008; accepted 13 October 2008     

Abduction aiming at empirical progress or eventruth approximationleading to a challenge for computational modelling

This paper primarily deals with theconceptual prospects for generalizing the aim ofabduction from the standard one of explainingsurprising or anomalous observations to that ofempirical progress or even truth approximation. Itturns out that the main abduction task then becomesthe instrumentalist task of theory revision aiming atan empirically more successful theory, relative to theavailable data, but not necessarily compatible withthem. The rest, that is, genuine empirical progress aswell as observational, referential and theoreticaltruth approximation, is a matter of evaluation andselection, and possibly new generation tasks forfurther improvement. The paper concludes with a surveyof possible points of departure, in AI and logic, forcomputational treatment of the instrumentalist taskguided by the `comparative evaluation matrix'.     

Of volatiles and peptides: in search for MHC-dependent olfactory signals in social communication

Genes of the major histocompatibility complex (MHC), which play a critical role in immune recognition, are considered to influence social behaviors in mice, fish, humans, and other vertebrates via olfactory cues. As studied most extensively in mice, the polymorphism of MHC class I genes is considered to bring about a specific scent signature, which is decoded by the olfactory system resulting in an individual-specific reaction such as mating. On the assumption that this signature resides in volatiles, extensive attempts to identify these MHC-specific components in urine failed. Alternatively, it has been suggested that peptide ligands of MHC class I molecules are released into urine and can elicit an MHC-haplotype-specific behavioral response after uptake into the nose by sniffing. Analysis of the urinary peptide composition of mice shows that MHC-derived peptides are present, albeit in extremely low concentrations. In contrast, urine contains abundant peptides which differ between mouse strains due to genomic variations such as single-nucleotide variations or complex polymorphisms in multigene families as well as in their concentration. Thus, urinary peptides represent a real-time sampling of the expressed genome available for sensory evaluation. It is suggested that peptide variation caused by genomic differences contains sufficient information for individual recognition beyond or instead of an influence of the MHC in mice and other vertebrates.     

Superconductors: time-reversal symmetry breaking?

One of the mysteries of modern condensed-matter physics is the nature of the pseudogap state of the superconducting cuprates. Kaminski et al. claim to have observed signatures of time-reversal symmetry breaking in the pseudogap regime in underdoped Bi2Sr2CaCu2O8+delta (Bi2212). Here we argue that the observed circular dichroism is due to the 51 superstructure replica of the electronic bands and therefore cannot be considered as evidence for spontaneous time-reversal symmetry breaking in cuprates.     

Mast cells stimulated by membrane-bound,but not soluble,steel factor are dependent on phospholipase C activation

The steel factor (SLF) and c-Kit growth factor/receptor pair are key molecules governing mast cell development and survival. SLF is expressed on stromal cells as a membrane-bound molecule (mSLF) which can be cleaved by proteases to release a soluble form (sSLF). We investigated the importance of phospholipase C (PLC) activation in mast cells stimulated by sSLF and mSLF. PLC antagonists U73122, neomycin sulfate and oleic acid inhibited mast cell thymidine incorporation stimulated by mSLF, but not by sSLF. These antagonists suppressed sSLF-induced Ca2+ transients but did not significantly interfere with c-Kit phosphorylation or PLC-gamma2 recruitment. p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase), was found to be efficiently recruited to c-Kit following stimulation by sSLF or mSLF. However PKB/Akt, a kinase activated by PI3-kinase products, was phosphorylated following sSLF stimulation, but not with mSLF. Taken together, these studies demonstrate the importance of PLC activation by mSLF in supporting mast cells.