Genome‐wide detection of CNVs associated with beak deformity in chickens using high‐density 600K SNP arrays

Beak deformity (crossed beaks) is found in several indigenous chicken breeds including Beijing‐You studied here. Birds with deformed beaks have reduced feed intake and poor production performance. Recently, copy number variation (CNV) has been examined in many species and is recognized as a source of genetic variation, especially for disease phenotypes. In this study, to unravel the genetic mechanisms underlying beak deformity, we performed genome‐wide CNV detection using Affymetrix chicken high‐density 600K data on 48 deformed‐beak and 48 normal birds using penncnv . As a result, two and eight CNV regions (CNVRs) covering 0.32 and 2.45 Mb respectively on autosomes were identified in deformed‐beak and normal birds respectively. Further RT‐qPCR studies validated nine of the 10 CNVRs. The ratios of six CNVRs were significantly different between deformed‐beak and normal birds (P < 0.01). Within these six regions, three and 21 known genes were identified in deformed‐beak and normal birds respectively. Bioinformatics analysis showed that these genes were enriched in six GO terms and one KEGG pathway. Five candidate genes in the CNVRs were further validated using RT‐qPCR. The expression of LRIG2 (leucine rich repeats and immunoglobulin like domains 2) was lower in birds with deformed beaks (P < 0.01). Therefore, the LRIG2 gene could be considered a key factor in view of its known functions and its potential roles in beak deformity. Overall, our results will be helpful for future investigations of the genomic structural variations underlying beak deformity in chickens.     

NdhO,a Subunit of NADPH Dehydrogenase,Destabilizes Medium Size Complex of the Enzyme in Synechocystis sp. Strain PCC 6803

Two mutants that grew faster than the wild-type (WT) strain under high light conditions were isolated from Synechocystis sp. strain PCC 6803 transformed with a transposon-bearing library. Both mutants had a tag in ssl1690 encoding NdhO. Deletion of ndhO increased the activity of NADPH dehydrogenase (NDH-1)-dependent cyclic electron transport around photosystem I (NDH-CET), while overexpression decreased the activity. Although deletion and overexpression of ndhO did not have significant effects on the amount of other subunits such as NdhH, NdhI, NdhK, and NdhM in the cells, the amount of these subunits in the medium size NDH-1 (NDH-1M) complex was higher in the ndhO-deletion mutant and much lower in the overexpression strain than in the WT. NdhO strongly interacts with NdhI and NdhK but not with other subunits. NdhI interacts with NdhK and the interaction was blocked by NdhO. The blocking may destabilize the NDH-1M complex and repress the NDH-CET activity. When cells were transferred from growth light to high light, the amounts of NdhI and NdhK increased without significant change in the amount of NdhO, thus decreasing the relative amount of NdhO. This might have decreased the blocking, thereby stabilizing the NDH-1M complex and increasing the NDH-CET activity under high light conditions.     

Localized reversible frameshift mutation in an adhesin gene confers a phase-variable adherence phenotype in mycoplasma

The variable adherence-associated (Vaa) antigen of Mycoplasma hominis is an abundant surface lipoprotein adhesin that may mediate important interactions of this wall-less prokaryotic pathogen with the human host. Extensive mutational variation of Vaa size, as well as sequence and antigenic divergence, has been described previously. Using a series of clonal isolates representing an isogenic lineage of variants oscillating in Vaa expression, Vaa is further shown in this study to undergo high-frequency phase variation in expression, which correlated precisely with the ability of M . hominis to adhere to cultured human cells. Although no DNA rearrangements or sequence differences in the 5' regions flanking vaa alleles were detected between Vaa⁺ and Vaa⁻ variants, intragenic vaa sequences from this lineage revealed an oscillating mutation involving a single nucleotide deletion/insertion in a short tract of adenine residues near the 5' end of the mature Vaa coding sequence, which created a translational frameshift resulting in either a complete Vaa ORF or an in-frame UAG stop codon immediately downstream of the poly-A tract. Evidence for the occurrence of this high-frequency frameshift mutation in vivo was obtained from analysis of PCR-generated vaa sequences amplified from the joint synovial fluid of a patient with M . hominis -associated arthritis, which indicated that Vaa phase variation occurs during M . hominis infection in the natural host. These results identify a distinctive frameshift mutator element in the vaa gene that governs M . hominis adherence and highlight the importance of mutational alteration of primary gene products on the mycoplasma surface as a means of generating and maintaining functional diversity in the host.     

Phrasal Paraphrase Based Question Reformulation for Archived Question Retrieval

Lexical gap in cQA search, resulted by the variability of languages, has been recognized as an important and widespread phenomenon. To address the problem, this paper presents a question reformulation scheme to enhance the question retrieval model by fully exploring the intelligence of paraphrase in phrase-level. It compensates for the existing paraphrasing research in a suitable granularity, which either falls into fine-grained lexical-level or coarse-grained sentence-level. Given a question in natural language, our scheme first detects the involved key-phrases by jointly integrating the corpus-dependent knowledge and question-aware cues. Next, it automatically extracts the paraphrases for each identified key-phrase utilizing multiple online translation engines, and then selects the most relevant reformulations from a large group of question rewrites, which is formed by full permutation and combination of the generated paraphrases. Extensive evaluations on a real world data set demonstrate that our model is able to characterize the complex questions and achieves promising performance as compared to the state-of-the-art methods.     

The Optimal Solution of a Non-Convex State-Dependent LQR Problem and Its Applications

This paper studies a Non-convex State-dependent Linear Quadratic Regulator (NSLQR) problem, in which the control penalty weighting matrix in the performance index is state-dependent. A necessary and sufficient condition for the optimal solution is established with a rigorous proof by Euler-Lagrange Equation. It is found that the optimal solution of the NSLQR problem can be obtained by solving a Pseudo-Differential-Riccati-Equation (PDRE) simultaneously with the closed-loop system equation. A Comparison Theorem for the PDRE is given to facilitate solution methods for the PDRE. A linear time-variant system is employed as an example in simulation to verify the proposed optimal solution. As a non-trivial application, a goal pursuit process in psychology is modeled as a NSLQR problem and two typical goal pursuit behaviors found in human and animals are reproduced using different control weighting . It is found that these two behaviors save control energy and cause less stress over Conventional Control Behavior typified by the LQR control with a constant control weighting , in situations where only the goal discrepancy at the terminal time is of concern, such as in Marathon races and target hitting missions.     

The Neural Basis of Responsibility Attribution in Decision-Making

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.     

Tampering with cancer chemoresistance by targeting the TGM2-IL6-autophagy regulatory network

Macroautophagy/autophagy is a well-established process involved in maintaining cellular homeostasis, but its role in cancer is complex and even controversial. Many studies have reported a correlative relationship between increased autophagy and evolving cancer cells under stress conditions such as nutrient or oxygen deprivation; however, there has been a lack of a plausible mechanistic link to properly target the autophagy process in the context of this microenvironment. We recently unveiled a positive regulatory loop involving TGM2 (transglutaminase 2)-NFKB/NF-κB signaling, IL6 and autophagy in cancer using mantle cell lymphoma (MCL) as a model system. These pathways are functionally connected to each other, thereby promoting malignant B cell survival and leading to enhanced lymphoma progression both in mice and in patients. Disruption of this network could provide an opportunity to increase the efficacies of current therapies and to reduce MCL drug resistance.