Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.     

Variation in the lactase dehydrogenase activity of the esophagus

Summary Quantitative assay and electrophroetic study of lactate dehydrogenase (LDH) from various tissues of the opossum esophagus were performed. On the basis of expression of the LDH isozymes, we concluded that the smooth muscle of the body of the esophagus carry on more anaerobic glycolysis than the striated muscle. The smooth muscle of the gastroesophageal junction carry on both anaerobic as well aerobic glycolysis.Acknowledgments. This work was supported by Kelsey-Leary Foundation grant No. 962, Houston, Texas. We appreciate the technical assistance of Henry D. Kasten, and Carol K. Kitson.     

Chlamydospore germination and artificial culture ofProtomyces macrosporus unger

Zusammenfassung Die Keimruhe der Chlamydosporen vonProtomyces macrosporus Unger, welcher aufCoriandrum sativum L. Stamm-Gallen erzeugt, kann durch künstliches Aufweichen der Exospore gebrochen werden. Der Pilz ist auf Kartoffel-Dextrose-Agar kultivierbar.     

Early differentiation and volatile accretion recorded in deep-mantle neon and xenon

The isotopes (129)Xe, produced from the radioactive decay of extinct (129)I, and (136)Xe, produced from extinct (244)Pu and extant (238)U, have provided important constraints on early mantle outgassing and volatile loss from Earth. The low ratios of radiogenic to non-radiogenic xenon ((129)Xe/(130)Xe) in ocean island basalts (OIBs) compared with mid-ocean-ridge basalts (MORBs) have been used as evidence for the existence of a relatively undegassed primitive deep-mantle reservoir. However, the low (129)Xe/(130)Xe ratios in OIBs have also been attributed to mixing between subducted atmospheric Xe and MORB Xe, which obviates the need for a less degassed deep-mantle reservoir. Here I present new noble gas (He, Ne, Ar, Xe) measurements from an Icelandic OIB that reveal differences in elemental abundances and (20)Ne/(22)Ne ratios between the Iceland mantle plume and the MORB source. These observations show that the lower (129)Xe/(130)Xe ratios in OIBs are due to a lower I/Xe ratio in the OIB mantle source and cannot be explained solely by mixing atmospheric Xe with MORB-type Xe. Because (129)I became extinct about 100 million years after the formation of the Solar System, OIB and MORB mantle sources must have differentiated by 4.45 billion years ago and subsequent mixing must have been limited. The Iceland plume source also has a higher proportion of Pu- to U-derived fission Xe, requiring the plume source to be less degassed than MORBs, a conclusion that is independent of noble gas concentrations and the partitioning behaviour of the noble gases with respect to their radiogenic parents. Overall, these results show that Earth's mantle accreted volatiles from at least two separate sources and that neither the Moon-forming impact nor 4.45 billion years of mantle convection has erased the signature of Earth's heterogeneous accretion and early differentiation.     

Effect of poly(vinyl pyrrolidone ) on the morph ology and physical properties of poly(vinyl alcohol) /sodium montmorill onite nanocompos ite films

Nanocomposites of poly(vinyl alcohol)(PVA),poly(vinyl pyrrolidone)(PVP) and sodium montmorillonite(Na~+MMT) were prepared by solution mixing and then cast into films.X-ray diffraction analysis and images of transmission electron microscopy establish the formation of PVA/Na~+MMT intercalated nanocomposite.Exfoliated and highly intercalated PVA/PVP/Na~+MMT nanocomposite formed in the presence of PVP.Inclusion of PVP in PVA/Na~+MMT matrix enhances the hydrogen bonding interactions between PVA and Na~+MMT and thus increases the mechanical properties and thermal stability of PVA/PVP/Na~+MMT nanocomposites compared to PVA/Na~+MMT nanocomposite.The interactions between PVA,PVP and Na~+MMT were established by the Fourier transform infrared spectroscopy.The moisture absorption tendency of both the PVA and PVA/PVP films reduced after the incorporation of Na~+MMT at 75%constant relative humidity.Differential scanning calorimetry studies show that the presence of PVP and Na~+MMT both are responsible for reducing the heat of fusion,and crystallinity of PVA.The flow behavior of the PVA,PVA/PVP and its nanocomposite solutions has been also studied.Water vapor permeability of PVA/PVP/Na~+MMT composite films decreased in the presence of nanoclay due to increasing tortuous paths for diffusion.     

Role of different system delays on ecological food chain dynamics: Mathematical modelling and analysis

<正> This paper studies a three tier ecological food chain model consisting of nutrient,autotroph,and herbivore populations.Regeneration of nutrient from dead autotroph and herbivore biomass bydecomposers present in the soil is included.The time required for maturation of the herbivore populationis incorporated as a distributed time delay.Next,the authors introduce the time lag requiredfor regeneration of nutrient from the dead herbivore as a discrete time delay.Stability and bifurcationbehavior of the one-and two-delay models are carried out and a comparative study of the significanceof these delays in controlling the system dynamics is performed.Numerical simulations are done tojustify analytical results.     

Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation

Chromatin insulators demarcate expression domains by blocking the cis effects of enhancers or silencers in a position-dependent manner. We show that the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation. Chromatin immunoprecipitation analysis showed that a poly(ADP-ribosyl)ation mark, which exclusively segregates with the maternal allele of the insulator domain in the H19 imprinting control region, requires the bases that are essential for interaction with CTCF. Chromatin immunoprecipitation-on-chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. An insulator trap assay showed that the insulator function of most of these CTCF target sites is sensitive to 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase activity. We suggest that poly(ADP-ribosyl)ation imparts chromatin insulator properties to CTCF at both imprinted and nonimprinted loci, which has implications for the regulation of expression domains and their demise in pathological lesions.     

The Accuracy of Non‐traditional versus Traditional Methods of Forecasting Lumpy Demand

Forecasting for inventory items with lumpy demand is difficult because of infrequent nonzero demands with high variability. This article developed two methods to forecast lumpy demand: an optimally weighted moving average method and an intelligent pattern‐seeking method. We compare them with a number of well‐referenced methods typically applied over the last 30 years in forecasting intermittent or lumpy demand. The comparison is conducted over about 200,000 forecasts (using 1‐day‐ahead and 5‐day‐ahead review periods) for 24 series of actual product demands across four different error measures. One of the most important findings of our study is that the two non‐traditional methods perform better overall than the traditional methods. We summarize results and discuss managerial implications. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparison of lysine and tryptophan catabolizing enzymes in rat and bovine tissues

Earlier studies indicate that alpha-aminoadipate aminotransferase (AadAT) and kynurenine aminotransferase (KAT) activities from rat tissues are associated with a single protein. However, our recent studies indicate that AadAT activity from bovine liver and kidney is not associated with KAT activity. To test whether the lysine and tryptophan catabolism in bovine tissues differ from that in rat tissues, we compared the activities of enzymes involved in lysine and tryptophan pathways in rat and bovine tissues. The activities of lysine catabolizing enzymes such as AadAT, lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase in the bovine tissues were significantly lower than those found in rat tissues. The activities of tryptophan catabolizing enzymes such as KAT and kynurenine hydroxylase in the bovine tissues were negligible as compared to those in rat tissues. The results suggest that lysine is degraded via the saccharopine pathway in the livers and kidneys of both species but the metabolism of tryptophan in bovine tissues may be different from that in rat tissues.