Genomic analyses provide comprehensive insights into the domestication of bast fiber crop ramie (Boehmeria nivea)

Ramie (Boehmeria nivea) is an economically important natural fiber-producing crop that has been cultivated for thousands of years in China; however, the evolution of this crop remains largely unknown. Here, we report a ramie domestication analysis based on genome assembly and resequencing of cultivated and wild accessions. Two chromosome-level genomes representing wild and cultivated ramie were assembled de novo. Numerous structural variations between two assemblies, together with the genetic variations from population resequencing, constituted a comprehensive genomic variation map for ramie. Domestication analysis identified 71 high-confidence selective sweeps comprising 320 predicted genes, and 29 genes from sweeps were associated with fiber growth in the expression. In addition, we identified seven genetic loci associated with the fiber yield trait in the segregated population derived from the crossing of two assembled accessions, and two of which showed an overlap with the selective sweeps. These findings indicated that bast fiber traits were focused on during the domestication history of ramie. This study sheds light on the domestication of ramie and provides a valuable resource for biological and breeding studies of this important crop.     

Follistatin-like 1: A dual regulator that promotes cardiomyocyte proliferation and fibrosis

Follistatin-like 1 (FSTL1) is a key factor in maintaining cardiac growth and development. It can be activated by exercise training and has a dual role in promoting cardiomyocyte proliferation and fibrosis, but its underlying mechanism is not fully understood. To elucidate the dual mechanism and target of FSTL1 regulating of cardiomyocyte proliferation and myocardial fibrosis, and the mechanism by which exercise-regulated FSTL1 improves cardiovascular disease, we explored the signal transduction pathway of FSTL1 promoting cardiomyocyte proliferation and fibrosis, and compared the effects of different modes of exercise on the dual role of FSTL1. We believe that the dual role of promoting cardiomyocyte proliferation and fibrosis may be related to the ratio of cardiomyocyte and myocardial interstitial cell proliferation, different stages of the disease, different degrees of fibrosis, immune repair process, and transforming growth factor-β activation. Compared with long-term excessive endurance exercise, moderate resistance exercise can activate cardiomyocyte proliferation pathway through FSTL1, which is one of the effective ways to prevent cardiovascular disease.     

Cell Shape Can Mediate the Spatial Organization of the Bacterial Cytoskeleton

The bacterial cytoskeleton guides the synthesis of cell wall and thus regulates cell shape. Because spatial patterning of the bacterial cytoskeleton is critical to the proper control of cell shape, it is important to ask how the cytoskeleton spatially self-organizes in the first place. In this work, we develop a quantitative model to account for the various spatial patterns adopted by bacterial cytoskeletal proteins, especially the orientation and length of cytoskeletal filaments such as FtsZ and MreB in rod-shaped cells. We show that the combined mechanical energy of membrane bending, membrane pinning, and filament bending of a membrane-attached cytoskeletal filament can be sufficient to prescribe orientation, e.g., circumferential for FtsZ or helical for MreB, with the accuracy of orientation increasing with the length of the cytoskeletal filament. Moreover, the mechanical energy can compete with the chemical energy of cytoskeletal polymerization to regulate filament length. Notably, we predict a conformational transition with increasing polymer length from smoothly curved to end-bent polymers. Finally, the mechanical energy also results in a mutual attraction among polymers on the same membrane, which could facilitate tight polymer spacing or bundling. The predictions of the model can be verified through genetic, microscopic, and microfluidic approaches.     

Real-Time dynamics of Ca2+, caspase-3/7, and morphological changes in retinal ganglion cell apoptosis under elevated pressure

Quantitative information on the dynamics of multiple molecular processes in individual live cells under controlled stress is central to the understanding of the cell behavior of interest and the establishment of reliable models. Here, the dynamics of the apoptosis regulator intracellular Ca(2+), apoptosis effector caspase-3/7, and morphological changes, as well as temporal correlation between them at the single cell level, are examined in retinal gangling cell line (differentiated RGC-5 cells) undergoing apoptosis at elevated hydrostatic pressure using a custom-designed imaging platform that allows long-term real-time simultaneous imaging of morphological and molecular-level physiological changes in large numbers of live cells (beyond the field-of-view of typical microscopy) under controlled hydrostatic pressure. This examination revealed intracellular Ca(2+) elevation with transient single or multiple peaks of less than 0.5 hour duration appearing at the early stages (typically less than 5 hours after the onset of 100 mmHg pressure) followed by gradual caspase-3/7 activation at late stages (typically later than 5 hours). The data reveal a strong temporal correlation between the Ca(2+) peak occurrence and morphological changes of neurite retraction and cell body shrinkage. This suggests that Ca(2+) elevation, through its impact on ion channel activity and water efflux, is likely responsible for the onset of apoptotic morphological changes. Moreover, the data show a significant cell-to-cell variation in the onset of caspase-3/7 activation, an inevitable consequence of the stochastic nature of the underlying biochemical reactions not captured by conventional assays based on population-averaged cellular responses. This real-time imaging study provides, for the first time, statistically significant data on simultaneous multiple molecular level changes to enable refinements and testing of models of the dynamics of mitochondria-mediated apoptosis. Further, the platform developed and the approach has direct significance to the study of a variety of signaling pathway phenomena.     

Proteomic,functional and motif‐based analysis of C‐terminal Src kinase‐interacting proteins

C‐terminal Src kinase (Csk) that functions as an essential negative regulator of Src family tyrosine kinases (SFKs) interacts with tyrosine‐phosphorylated molecules through its Src homology 2 (SH2) domain, allowing it targeting to the sites of SFKs and concomitantly enhancing its kinase activity. Identification of additional Csk‐interacting proteins is expected to reveal potential signaling targets and previously undescribed functions of Csk. In this study, using a direct proteomic approach, we identified 151 novel potential Csk‐binding partners, which are associated with a wide range of biological functions. Bioinformatics analysis showed that the majority of identified proteins contain one or several Csk‐SH2 domain‐binding motifs, indicating a potentially direct interaction with Csk. The interactions of Csk with four proteins (partitioning defective 3 (Par3), DDR1, SYK and protein kinase C iota) were confirmed using biochemical approaches and phosphotyrosine 1127 of Par3 C‐terminus was proved to directly bind to Csk‐SH2 domain, which was consistent with predictions from in silico analysis. Finally, immunofluorescence experiments revealed co‐localization of Csk with Par3 in tight junction (TJ) in a tyrosine phosphorylation‐dependent manner and overexpression of Csk, but not its SH2‐domain mutant lacking binding to phosphotyrosine, promoted the TJ assembly in Madin‐Darby canine kidney cells, implying the involvement of Csk‐SH2 domain in regulating cellular TJs. In conclusion, the newly identified potential interacting partners of Csk provided new insights into its functional diversity in regulation of numerous cellular events, in addition to controlling the SFK activity.     

The regulation of NONO by USP11 via deubiquitination is linked to the proliferation of melanoma cells

Ubiquitin-specific protease 11 (USP11) has been implicated in the regulation of DNA repair, apoptosis, signal transduction and cell cycle. It belongs to a USP subfamily of deubiquitinases. Although previous research has shown that USP11 overexpression is frequently found in melanoma and is correlated with a poor prognosis, the potential molecular mechanism of USP11 in melanoma remains indefinitive. Here, we report that USP11 and NONO colocalize and interact with each other in the nucleus of melanoma cells. As a result, the knockdown of USP11 decreases NONO levels. Whereas, overexpression of USP11 increases NONO levels in a dose-dependent manner. Furthermore, we reveal that USP11 protects NONO protein from proteasome-mediated degradation by removing poly-ubiquitin chains conjugated onto NONO. Functionally, USP11 mediated melanoma cell proliferation via the regulation of NONO levels because ablation of USP11 inhibits the proliferation which could be rescued by ectopic expression of NONO protein. Moreover, a significant positive correlation between USP11 and NONO concentrations was found in clinical melanoma samples. Collectively, these results demonstrate that USP11 is a new deubiquitinase of NONO and that the signalling axis of USP11-NONO is significantly involved in melanoma proliferation.     

Brain Activation of Identity Switching in Multiple Identity Tracking Task

When different objects switch identities in the multiple identity tracking (MIT) task, viewers need to rebind objects’ identity and location, which requires attention. This rebinding helps people identify the regions targets are in (where they need to focus their attention) and inhibit unimportant regions (where distractors are). This study investigated the processing of attentional tracking after identity switching in an adapted MIT task. This experiment used three identity-switching conditions: a target-switching condition (where the target objects switched identities), a distractor-switching condition (where the distractor objects switched identities), and a no-switching condition. Compared to the distractor-switching condition, the target-switching condition elicited greater activation in the frontal eye fields (FEF), intraparietal sulcus (IPS), and visual cortex. Compared to the no-switching condition, the target-switching condition elicited greater activation in the FEF, inferior frontal gyrus (pars orbitalis) (IFG-Orb), IPS, visual cortex, middle temporal lobule, and anterior cingulate cortex. Finally, the distractor-switching condition showed greater activation in the IFG-Orb compared to the no-switching condition. These results suggest that, in the target-switching condition, the FEF and IPS (the dorsal attention network) might be involved in goal-driven attention to targets during attentional tracking. In addition, in the distractor-switching condition, the activation of the IFG-Orb may indicate salient change that pulls attention away automatically.