PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.     

The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD.     

Inflammasomes: current understanding and open questions

The innate immune system relies on its capability to detect invading microbes, tissue damage, or stress via evolutionarily conserved receptors. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family of pattern recognition receptors includes several proteins that drive inflammation in response to a wide variety of molecular patterns. In particular, the NLRs that participate in the formation of a molecular scaffold termed the “inflammasome” have been intensively studied in past years. Inflammasome activation by multiple types of tissue damage or by pathogen-associated signatures results in the autocatalytic cleavage of caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines, most importantly interleukin (IL)-1β and IL-18. Here, we review the current knowledge of mechanisms leading to the activation of inflammasomes. In particular, we focus on the controversial molecular mechanisms that regulate NLRP3 signaling and highlight recent advancements in DNA sensing by the inflammasome receptor AIM2.     

‘Public’ Science: Hydrogen Balloons and Lavoisier's Decomposition of Water

The balloon mania between 1783 and 1785 put an extraordinary strain on the Paris Academy of Sciences, threatening its status as the highest tribunal of European science. Faced with repeated royal directives and public frenzy, the Academy manoeuvred carefully to steer the research toward the hydrogen balloon and thereby to maintain its scientific superiority. Antoine-Laurent Lavoisier seized this moment when the promise of ‘the empire of airs’ brought science to the centre of public attention to push his theoretical reform for chemistry. He utilized the established protocol of the Academy and the resources of the Republic of Letters to broadly publicize his first decomposition of water in April 1784. Once he attained the publicity and the balloon fever began to cool, he staged a much more elaborate experiment for the experts in February 1785. Although this second, large-scale experiment cost much expense and effort, Lavoisier never published a full account. The differential care given to the two experiments can only be understood in their divergent rhetorical contexts. The written accounts in 1784 addressed the court of public opinion, while the exclusive performance in 1785 aimed at the court of experts to inaugurate the collaborative phase of the Chemical Revolution.     

Construction of protograph LDPC codes with circular generator matrices

The application of protograph low density parity check(LDPC) codes involves the encoding complexity problem.Since the generator matrices are dense,and if the positions of "1" s are irregularity,the encoder needs to store every "1" of the generator matrices by using huge chip area.In order to solve this problem,we need to design the protograph LDPC codes with circular generator matrices.A theorem concerning the circulating property of generator matrices of nonsingular protograph LDPC codes is proposed.The circulating property of generator matrix of nonsingular protograph LDPC codes can be obtained from the corresponding quasi-cyclic parity check matrix.This paper gives a scheme of constructing protograph LDPC codes with circulating generator matrices,and it reveals that the fast encoding algorithm of protograph LDPC codes has lower encoding complexity under the condition of the proposed theorem.Simulation results in additive white Gaussian noise(AWGN) channels show that the bit error rate(BER) performance of the designed codes based on the proposed theorem is much better than that of GB20600 LDPC codes and Tanner LDPC codes.     

Birds of a Feather Protest Together: Theorizing Self-Organizing Political Protests with Flock Theory

The current research theorizes decentralized and self-organized political protests via flock theory (Rosen 2002), a theory of emergent self-organization in communicative human interaction. Flock theory draws from a theoretical basis of emergence and self-organizing systems, and is presented as a theory of decentralized communication structures. Focusing on the optimization of decentralized networks and roadmap based coordination of organizationally homopholous foci; the current theory poses a model of human interaction that captures the potentially egalitarian effects of cooperative evolution and collective action. Case studies of two separate decentralized political protests against Korean government and FARC are offered as evidences of such phenomena.     

A novel cyclin encoded by a bcl1-linked candidate oncogene

We have previously identified a candidate oncogene (PRAD1 or D11S287E) on chromosome 11q13 which is clonally rearranged with the parathyroid hormone locus in a subset of benign parathyroid tumours. We now report that a cloned human placental PRAD1 complementary DNA encodes a protein of 295 amino acids with sequence similarities to the cyclins. Cyclins can form a complex with and activate p34cdc2 protein kinase, thereby regulating progress through the cell cycle. PRAD 1 messenger RNA levels vary dramatically across the cell cycle in HeLa cells. Addition of the PRAD1 protein to interphase clam embryo lysates containing inactive p34cdc2 kinase and lacking endogenous cyclins allows it to be isolated using beads bearing p13suc1, a yeast protein that binds cdc2 and related kinases with high affinity and coprecipitates kinase-associated proteins. Addition of PRAD1 also induces phosphorylation of histone H1, a preferred substrate of cdc2. These data suggest that PRAD1 encodes a novel cyclin whose overexpression may play an important part in the development of various tumours with abnormalities in 11q13.     

用单个摄像机获取三维视觉信息的一种方法

讨论了在平面坐标系上摄像机的标定和利用单个摄像机获取三维视觉信息的一种方法。实验结果表明，采用单个摄像机获取三维视觉信息的精度与摄像机相对目标物体的高度及对象物本身的厚度有关，在视场范围内，对象物的厚度越小，摄像机坐标中心相对于目标物体表面中心的距离越远，定位精度越好。