Selection of Cashmere Fineness Functional Genes by Translatomics

Cashmere fineness is an important index to evaluate cashmere quality. Liaoning Cashmere Goat (LCG) has a large cashmere production and long cashmere fiber, but its fineness is not ideal. Therefore, it is important to find genes involved in cashmere fineness that can be used in future endeavors aiming to improve this phenotype. With the continuous advancement of research, the regulation of cashmere fineness has made new developments through high-throughput sequencing and genome-wide association analysis. It has been found that translatomics can identify genes associated with phenotypic traits. Through translatomic analysis, the skin tissue of LCG sample groups differing in cashmere fineness was sequenced by Ribo-seq. With these data, we identified 529 differentially expressed genes between the sample groups among the 27197 expressed genes. From these, 343 genes were upregulated in the fine LCG group in relation to the coarse LCG group, and 186 were downregulated in the same relationship. Through GO enrichment analysis and KEGG enrichment analysis of differential genes, the biological functions and pathways of differential genes can be found. In the GO enrichment analysis, 491 genes were significantly enriched, and the functional region was mainly in the extracellular region. In the KEGG enrichment analysis, the enrichment of the human papillomavirus infection pathway was seen the most. We found that the COL6A5 gene may affect cashmere fineness.

Slow conformational changes of blue light sensor BLUF proteins in milliseconds

BLUF (blue light sensor using flavin) proteins consist of flavin-binding BLUF domains and functional domains. Upon blue light excitation, the hydrogen bond network around the flavin chromophore changes, and the absorption spectrum in the visible region exhibits red-shift. Ultimately, the light information received in the BLUF domain is transmitted to the functional region. It has been believed that this red-shift is complete within nanoseconds. Contrary to this commonly accepted scheme, in this study, slow reaction kinetics were discovered in milliseconds (τ1- and τ2-phase) for all the BLUF proteins examined (AppA, OaPAC, BlrP1, YcgF, PapB, SyPixD, and TePixD). Despite extensive reports on BLUF, this is the first clear observation of the BLUF protein absorption change with the duration in the millisecond time region. From the measurements of some domain-deleted mutants of OaPAC and two chimeric mutants of PixD proteins, it was found that the slower dynamics (τ2-phase) are strongly affected by the size and nature of the C-terminal region adjacent to the BLUF domain. Hence, this millisecond reaction is a significant indicator of conformational changes in the C-terminal region, which is essential for the biological functions. On the other hand, the τ1-phase commonly exists in all BLUF proteins, including any mutants. The origin of the slow dynamics was studied using site-specific mutants. These results clearly show the importance of Trp in the BLUF domain. Based on this, a reaction scheme for the BLUF reaction is proposed.

Multi-model mapping of phonemic fluency

The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analyses approaches. We investigated a large number of patients with focal unilateral right or left frontal (n = 110) or posterior (n = 100) or subcortical (n = 65) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcel-based lesion symptom mapping, tract-wise statistical analysis as well as Bayesian multivariate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcel-based lesion symptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multivariate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localised left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of energization, which sustains activation for the duration of the task and middle and inferior frontal regions concerned with selection, required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes.

Identification and Application of BhAPRR2 Controlling Peel Colour in Wax Gourd (Benincasa hispida)

Peel color is an important factor affecting commodity quality in vegetables; however, the genes controlling this trait remain unclear in wax gourd. Here, we used two F2 genetic segregation populations to explore the inheritance patterns and to clone the genes associated with green and white skin in wax gourd. The F2 and BC1 trait segregation ratios were 3:1 and 1:1, respectively, and the trait was controlled by nuclear genes. Bulked segregant analysis of both F2 plants revealed peaks on Chr5 exceeding the confidence interval. Additionally, 6,244 F2 plants were used to compress the candidate interval into a region of 179 Kb; one candidate gene, Bch05G003950 (BhAPRR2), encoding two-component response regulator-like protein Arabidopsis pseudo-response regulator2 (APRR2), which is involved in the regulation of peel color, was present in this interval. Two bases (GA) present in the coding sequence of BhAPRR2 in green-skinned wax gourd were absent from white-skinned wax gourd. The latter contained a frameshift mutation, a premature stop codon, and lacked 335 residues required for the protein functional region. The chlorophyll content and BhAPRR2 expression were significantly higher in green-skinned than in white-skinned wax gourd. Thus, BhAPRR2 may regulate the peel color of wax gourd. This study provides a theoretical foundation for further studies of the mechanism of gene regulation for the fruit peel color of wax gourd.

A small regulatory RNA alters Staphylococcus aureus virulence by titrating RNAIII activity

Staphylococcus aureus is an opportunistic human and animal pathogen with an arsenal of virulence factors that are tightly regulated during bacterial infection. The latter is achieved through a sophisticated network of regulatory proteins and regulatory RNAs. Here, we describe the involvement of a novel prophage-carried small regulatory S. aureus RNA, SprY, in the control of virulence genes. An MS2-affinity purification assay reveals that SprY forms a complex in vivo with RNAIII, a major regulator of S. aureus virulence genes. SprY binds to the 13th stem-loop of RNAIII, a key functional region involved in the repression of multiple mRNA targets. mRNAs encoding the repressor of toxins Rot and the extracellular complement binding protein Ecb are among the targets whose expression is increased by SprY binding to RNAIII. Moreover, SprY decreases S. aureus hemolytic activity and virulence. Our results indicate that SprY titrates RNAIII activity by targeting a specific stem loop. Thus, we demonstrate that a prophage-encoded sRNA reduces the pathogenicity of S. aureus through RNA sponge activity.

Placental mammals acquired the functional region and domain in NRK for regulating the CK2-PTEN-AKT pathway and placental cell proliferation

The molecular evolution processes underlying the acquisition of the placenta in eutherian ancestors are not fully understood. Mouse NCK-interacting kinase (NIK)-related kinase (NRK) is expressed highly in the placenta and plays a role in preventing placental hyperplasia. Here, we show the molecular evolution of NRK, which confers its function for inhibiting placental cell proliferation. Comparative genome analysis identified NRK orthologues across vertebrates, which share the kinase and citron homology (CNH) domains. Evolutionary analysis revealed that NRK underwent extensive amino acid substitutions in the ancestor of placental mammals and has been since conserved. Biochemical analysis of mouse NRK revealed that the CNH domain binds to phospholipids, and a region in NRK binds to and inhibits casein kinase-2 (CK2), which we named the CK2-inhibitory region (CIR). Cell culture experiments suggest the following: (1) mouse NRK is localised at the plasma membrane via the CNH domain, where the CIR inhibits CK2. (2) This mitigates CK2-dependent phosphorylation and inhibition of PTEN, and (3) leads to the inhibition of AKT signalling and cell proliferation. Nrk deficiency increased phosphorylation levels of PTEN and AKT in mouse placenta, supporting our hypothesis. Unlike mouse NRK, chicken NRK did not bind to phospholipids and CK2, decrease phosphorylation of AKT, or inhibit cell proliferation. Both the CNH domain and CIR have evolved under purifying selection in placental mammals. Taken together, our study suggests that placental mammals acquired the phospholipid-binding CNH domain and CIR in NRK for regulating the CK2-PTEN-AKT pathway and placental cell proliferation.

A Dynamic Model of Cytosolic Calcium Concentration Oscillations in Mast Cells

In this paper, a dynamic model of cytosolic calcium concentration () oscillations is established for mast cells (MCs). This model includes the cytoplasm (Cyt), endoplasmic reticulum (ER), mitochondria (Mt), and functional region (μd), formed by the ER and Mt, also with channels in these cellular compartments. By this model, we calculate oscillations that are driven by distinct mechanisms at varying (degradation coefficient of inositol 1, 4, 5-trisphosphate, and production coefficient of ), as well as at different distances between the ER and Mt (ER–Mt distance). The model predicts that (i) Mt and μd compartments can reduce the amplitude of oscillations, and cause the ER to release less during oscillations; (ii) with increasing cytosolic concentration (), the amplitude of oscillations increases (from 0.1 μM to several μM), but the frequency decreases; (iii) the frequency of oscillations decreases as the ER–Mt distance increases. What is more, when the ER–Mt distance is greater than 65 nm, the μd compartment has less effect on oscillations. These results suggest that Mt, μd, and can all affect the amplitude and frequency of oscillations, but the mechanism is different. The model provides a comprehensive mechanism for predicting cytosolic concentration oscillations in mast cells, and a theoretical basis for calcium oscillations observed in mast cells, so as to better understand the regulation mechanism of calcium signaling in mast cells.

Rolling controls sperm navigation in response to the dynamic rheological properties of the environment

Mammalian sperm rolling around their longitudinal axes is a long-observed component of motility, but its function in the fertilization process, and more specifically in sperm migration within the female reproductive tract, remains elusive. While investigating bovine sperm motion under simple shear flow and in a quiescent microfluidic reservoir and developing theoretical and computational models, we found that rolling regulates sperm navigation in response to the rheological properties of the sperm environment. In other words, rolling enables a sperm to swim progressively even if the flagellum beats asymmetrically. Therefore, a rolling sperm swims stably along the nearby walls (wall-dependent navigation) and efficiently upstream under an external fluid flow (rheotaxis). By contrast, an increase in ambient viscosity and viscoelasticity suppresses rolling, consequently, non-rolling sperm are less susceptible to nearby walls and external fluid flow and swim in two-dimensional diffusive circular paths (surface exploration). This surface exploration mode of swimming is caused by the intrinsic asymmetry in flagellar beating such that the curvature of a sperm’s circular path is proportional to the level of asymmetry. We found that the suppression of rolling is reversible and occurs in sperm with lower asymmetry in their beating pattern at higher ambient viscosity and viscoelasticity. Consequently, the rolling component of motility may function as a regulatory tool allowing sperm to navigate according to the rheological properties of the functional region within the female reproductive tract.

Automatic delimitation of labour market areas based on multi-criteria optimisation: The case of Spain 2011

Labour market areas (LMAs) are a type of functional region (FR) defined on commuting flows and used in many countries to serve as the territorial reference for regional studies and policy making at local levels. Existing methods rely on manual adjustments of the results to ensure high quality, making them difficult to be monitored, hard to apply to different territories, and onerous to produce in terms of required work-hours. We propose an approach to automatise all stages of the delineation procedure and improve the final results, building upon a state-of-the-art stochastic search procedure that ensures optimal allocation of municipalities/counties to LMAs while keeping good global indicators: a pre-processing layer clusters adjoining municipalities with strong commuting flows to constrain the initial search space of the stochastic search, and a multi-criteria heuristic corrects common deficiencies that derive from global maximisation approaches or simple greedy heuristics. It produces high quality LMAs with optimal local characteristics. To demonstrate this methodology and assess the improvement achieved, we apply it to define LMAs in Spain based on the latest commuting data.