Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair

The genetic determinants of hair texture in humans are largely unknown. Several human syndromes exist in which woolly hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly hair has only rarely been reported. To identify a gene involved in controlling hair texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2-14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein-coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining hair texture in humans.     

Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity

The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca overexpression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity.     

Transmit Power Optimization for Relay-Aided Multi-Carrier D2D Communication

In this paper,we consider the power optimization problem in Orthogonal Frequency Division Multiplexing(OFDM)-based relay-enhanced device-to-device(D2D) communication.In a single cell transmission scenario,dualhop communication is assumed in which each D2D user re-uses the spectrum of just one Cellular User(CU).In this work,we formulate a joint optimization scheme under a Decode-and-Forward(DF) relaying protocol to maximize the sum throughput of D2D and cellular networks via power allocation over different sub-carriers.The problem is thus transformed into a standard convex optimization,subject to individual power constraints at different transmitting nodes.We exploit the duality theory to decompose the problem into several sub-problems and use Karush–Kuhn–Tucker(KKT) conditions to solve each sub-problem.We provide simulation results to validate the performance of our proposed scheme.     

Structural Decomposition Analysis to Investigate the Changes in Energy Consumption in Pakistan

The world energy demand is increasing due to rapid growth in the global economy, industrialization, and urbanization. Pakistan is also confronted with increasing energy demand on one hand and is confronted with the challenge of energy demand-supply gap on the other hand. Since energy is the major driver for growth, it becomes important to investigate the trends of energy consumption in a country and the factors that are most affecting the changes in the use of energy. This particular study aims to investigate the use of energy by all the economic sectors of Pakistan during 2000–2012.The major contribution is the first time application of structural decomposition analysis(SDA) for energy usage along with using Input-Output data for the period of 2002–2012. The results show the fluctuation of the energy intensity of the sectors throughout the study period. Also, the overall effect of energy intensity is negative on energy consumption and it shows a negative contribution value of-80.90% for the study period. Furthermore, the focus on more energy-intensive products like cement,automobiles, iron, steel products and the increasing final demand of the economy contributes to the growth of energy consumption in Pakistan during 2000–2012.     

Influence of alkaline treatment and fiber loading on the physical and mechanical properties of kenaf/polypropylene composites for variety of applications

Due to current trend and increasing interest towards natural based fiber products, Kenaf (Hibiscus cannabinus) fibers have been used for the developments of many products. Therefore, Kenaf fiber-reinforced composites have been widely used in engineering and industrial applications. The present work deals with the fabricating and characterization of untreated and treated kenaf/polypropylene (PP)-reinforced composites. Composites of PP reinforced with treated and untreated kenaf fibers were fabricated using the injection molding technique. Different fiber loadings of 10, 20, 30, 40, 50 wt% treated and untreated kenaf composites were also prepared. X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis (TGA) were performed on the treated, untreated kenaf fibers and kenaf/PP composites. Moreover, the alkaline-treated kenaf composites exhibit better physical, morphological, and mechanical properties because of the compatibility of kenaf with PP. However, variations in tensile and flexural properties depend on treatment and kenaf fiber contents. The percentage increase in the mechanical properties of the treated kenaf/PP composites relative to that of PP was also measured. In addition, 40 wt% kenaf fiber loading resulted in higher mechanical properties. By contrast, kenaf/PP composite with 50% fiber loading was not successfully prepared because of improper mixing and the burning of kenaf fibers in the PP matrix. To conclude, 40% kenaf/PP composites with superior physical and mechanical properties may be used in variety of applications such as automotive, sports, construction, animal bedding, and mass production industries.     

Rationalization of Metaphorical Exploration: Improving the Creativity Phase of Total Systems Intervention (TSI) on the Basis of Theory and Practice

Metaphors play a significant role in the creativity phase of Total Systems Intervention (TSI). They help managers and other stakeholders to think creatively about their organizations and to highlight their organizational problems. However, in the current form of the creativity phase of TSI there are no explicit criteria in the selection of metaphors or in the disclosure and prioritization of organizational issues. This paper seeks to open a dialog with management consultants who might be interested in the consulting meta-methodology called TSI. It proposes the creativity phase of TSI to management consultants along with the theoretical improvements, as well as the context-dependent and conditional practical innovations. It emphasizes my reflections about the potential of this stage in the appreciation of organizational problems and invites new modifications. To reach this aim, the paper initially gives a brief account of the creativity phase of TSI, deals with its shortcomings, highlights its theoretical improvements and empirical findings in the PALMEK manufacturing company, Turkey, and then rationalizes this phase through proposing an appropriate method for its implementation. This method, on the whole, facilitates systematic and comprehensive analyses of problem situations, characterization of organizational issues, and disclosure and prioritization of concealed organizational problems in a structured and democratic conversational setting.     

A discoidin domain receptor 1 knock-out mouse as a novel model for osteoarthritis of the temporomandibular joint

Discoidin domain receptor 1 (DDR-1)-deficient mice exhibited a high incidence of osteoarthritis (OA) in the temporomandibular joint (TMJ) as early as 9 weeks of age. They showed typical histological signs of OA, including surface fissures, loss of proteoglycans, chondrocyte cluster formation, collagen type I upregulation, and atypical collagen fibril arrangements. Chondrocytes isolated from the TMJs of DDR-1-deficient mice maintained their osteoarthritic characteristics when placed in culture. They expressed high levels of runx-2 and collagen type I, as well as low levels of sox-9 and aggrecan. The expression of DDR-2, a key factor in OA, was increased. DDR-1-deficient chondrocytes from the TMJ were positively influenced towards chondrogenesis by a three-dimensional matrix combined with a runx-2 knockdown or stimulation with extracellular matrix components, such as nidogen-2. Therefore, the DDR-1 knock-out mouse can serve as a novel model for temporomandibular disorders, such as OA of the TMJ, and will help to develop new treatment options, particularly those involving tissue regeneration.     

Molecular evolution of rice S 5 n and functional comparison among different sequences

The wide compatibility gene, S ₅ ⁿ , can overcome embryo sac sterility between indica and japonica subspecies of rice. Therefore, it is very important to characterize the features of the S ₅ ⁿ sequence to reveal the origin and evolution of S ₅ ⁿ . In this paper, 26 cultivated rice haplotypes and 22 wild rice accessions harboring S ₅ ⁿ were used to sequence S ₅ ⁿ . The results showed that 15 genotypes among the 48 materials were fully consistent with control cultivar 02428 (CK). The other 33 accessions had different degrees of variation in the S ₅ ⁿ sequence. Variations in the coding region mainly occurred in the second exon and eight materials showed a 10-bp deletion at 1710?C1719 bp, including wild (O. nivara) and cultivated rice, such as IRW501 and Yuetai B. S ₅ ⁿ sequences were not biased and evolved neutrally. The 48 materials could be divided into 4 categories using a phylogenetic tree of the amino acid sequences. Most of the wild rice clustered together, and the cultivated rice clustered into another group. Eight cultivated rice and O. nivara (wild rice) clustered in another group, which were found to lack 10 consecutive bases in exon 2. Eight rice varieties with high numbers of differences in their S ₅ ⁿ coding regions were crossed with testers (typically indica and japonica) to produced test cross F₁ populations. The F₁s were examined for their ability to overcome indica-japonica hybrid sterility. The result showed that the embryo sac fertility of S ₅ ⁿ -containing hybrids increased significantly compared with control hybrids, but there were no differences among the materials with divergent sequences, indirectly proving that S ₅ ⁿ is a non-functional gene.