Keratins in Skin Epidermal Development and Diseases

Epidermal keratinocyte (KC), the major cell type in the skin epidermis, plays critical roles in forming a permeability barrier to separate internal organs from external stimuli. Keratins, constituting about 30–80% of the total protein in KCs, form the major intermediate filament cytoskeleton of KC. Keratins consist of 54 unique genes in humans and they are expressed in cell-, differentiation- and development-dependent manner. While keratin pairs K5-K14 and K1-K10 are normally associated with KCs at different cell differentiation stages, other keratin pairs such as K6-K16/K17 and K8–K18 and are usually not expressed in normal skin interfollicular epidermis, but are elevated during wounding, inflammatory skin diseases such as psoriasis or malignant conversion of KC. The expression and function of keratins are tightly regulated at both transcriptional and post-transcriptional levels. Inherited or spontaneous mutations in keratins or abnormal keratin regulations or modifications can cause KC and cutaneous tissue fragility, skin hypertrophic and inflammatory conditions or malignant transformation of KC, therefore accounting for a large number of disorders in human skin. Here we review the recent literature on how keratins are normally expressed during skin development and how mutations or misregulations of these keratins are involved in the pathogenesis of skin diseases

Robust functional principal components: A projection-pursuit approach

In many situations, data are recorded over a period of time and may be regarded as realizations of a stochastic process. In this paper, robust estimators for the principal components are considered by adapting the projection pursuit approach to the functional data setting. Our approach combines robust projection-pursuit with different smoothing methods. Consistency of the estimators are shown under mild assumptions. The performance of the classical and robust procedures are compared in a simulation study under different contamination schemes.Comment: Published in at http://dx.doi.org/10.1214/11-AOS923 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Predicting the schedule and cost performance in public school building projects in Taiwan

The Ministry of Education (MOE) of Taiwan invests about NTD 30 billion a year in Public School Building Projects (PSBPs). However, 95% of the PSBPs have been extended and have incurred increased costs. A PSBP performance evaluation and prediction system was established by using the Fuzzy Delphi Method (FDM), association rules and an Artificial Neural Network (ANN). Sixty-two Taiwanese PSBPs were used as the samples, while eleven high correlation factors that influence the project performance of PSBPs were defined, and the reasons leading to the poor project performance were discussed in this study. Moreover, the results of the test cases operated by ANN showed that the accuracy rate for schedule and cost variability predictions can reach 84%. The high accuracy rate indicated the reliability of priority control for high-risk projects in the future. The proposed approach can be provided to clients, design and construction firms, and project managers to understand the project performance in real time and to establish a dynamic tracking review and response measures for improving the overall project satisfaction. First published online 20 December 202

Generation of Oligodendrocyte Progenitor Cells From Mouse Bone Marrow Cells.

Oligodendrocyte progenitor cells (OPCs) are a subtype of glial cells responsible for myelin regeneration. Oligodendrocytes (OLGs) originate from OPCs and are the myelinating cells in the central nervous system (CNS). OLGs play an important role in the context of lesions in which myelin loss occurs. Even though many protocols for isolating OPCs have been published, their cellular yield remains a limit for clinical application. The protocol proposed here is novel and has practical value; in fact, OPCs can be generated from a source of autologous cells without gene manipulation. Our method represents a rapid, and high-efficiency differentiation protocol for generating mouse OLGs from bone marrow-derived cells using growth-factor defined media. With this protocol, it is possible to obtain mature OLGs in 7-8 weeks. Within 2-3 weeks from bone marrow (BM) isolation, after neurospheres formed, the cells differentiate into Nestin+ Sox2+ neural stem cells (NSCs), around 30 days. OPCs specific markers start to be expressed around day 38, followed by RIP+O4+ around day 42. CNPase+ mature OLGs are finally obtained around 7-8 weeks. Further, bone marrow-derived OPCs exhibited therapeutic effect in shiverer (Shi) mice, promoting myelin regeneration and reducing the tremor. Here, we propose a method by which OLGs can be generated starting from BM cells and have similar abilities to subventricular zone (SVZ)-derived cells. This protocol significantly decreases the timing and costs of the OLGs differentiation within 2 months of culture

Membrane repair against H. pylori promotes cancer cell proliferation

Membrane repair is a universal response against physical and biological insults and enables cell survival. Helicobacter pylori is one of the most common human pathogens and the first formally recognized bacterial carcinogen associated with gastric cancer. However, little is known about host membrane repair in the context of H. pylori infection. Here we show that H. pylori disrupts the host plasma membrane and induces Ca2+ influx, which triggers the translocation of annexin family members A1 and A4 to the plasma membrane. This in turn activates a membrane repair response through the recruitment of lysosomal membranes and the induction of downstream signaling transduction pathways that promote cell survival and proliferation. Based on our data, we propose a new model by which H. pylori infection activates annexin A1 and A4 for membrane repair and how annexin A4 over-expression induced signaling promotes cell proliferation. Continual activation of this membrane repair response signaling cascade may cause abnormal cellular states leading to carcinogenesis. This study links H. pylori infection to membrane repair, providing insight into potential mechanisms of carcinogenesis resulting from membrane damage

Ethyl 3-[2-(p-tolyl­carbamothio­yl)hydrazinyl­idene]butano­ate

The title compound, C14H19N3O2S, was obtained from a condensation reaction of N-(p-tol­yl)hydrazinecarbothio­amide and ethyl acetoacetate. The mol­ecule assumes an E configuration; the thio­semicarbazide and ester groups are located on the opposite sides of the C=N bond. The almost planar thio­semicarbazide unit (r.m.s. deviation = 0.0130 Å) is tilted at a dihedral angle of 49.54 (12)° with respect to the benzene ring. Inter­molecular N—H⋯N and N—H⋯S hydrogen bonding stabilizes the crystal structure. The eth­oxy group of the ester unit is disordered over two positions, with a site-occupancy ratio of 0.680 (10):0.320 (10)