Intracellular signalling and intercellular coupling coordinate heterogeneous contractile events to facilitate tissue folding

Cellular forces generated in the apical domain of epithelial cells reshape tissues. Recent studies highlighted an important role for dynamic actomyosin contractions, called pulses, that change cell and tissue shape. Net cell shape change depends on whether cell shape is stabilized, or ratcheted, between pulses. Whether there are different classes of contractile pulses in wild-type embryos and how pulses are spatiotemporally coordinated is unknown. Here we develop a computational framework to identify and classify pulses and determine how pulses are coordinated during invagination of the Drosophila ventral furrow. We demonstrate biased transitions in pulse behaviour, where weak or unratcheted pulses transition to ratcheted pulses. The transcription factor Twist directs this transition, with cells in Twist-depleted embryos exhibiting abnormal reversed transitions in pulse behaviour. We demonstrate that ratcheted pulses have higher probability of having neighbouring contractions, and that ratcheting of pulses prevents competition between neighbouring contractions, allowing collective behaviour.National Institute of General Medical Sciences (U.S.) (Grant R00GM089826)National Institute of General Medical Sciences (U.S.) (Grant R01GM105984

Cyclin D-Cdk4,6 Drives Cell-Cycle Progression via the Retinoblastoma Protein's C-Terminal Helix.

The cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein Rb, which inhibits cell-cycle progression until its inactivation by phosphorylation. However, the role of Rb phosphorylation by cyclin D-Cdk4,6 in cell-cycle progression is unclear because Rb can be phosphorylated by other cyclin-Cdks, and cyclin D-Cdk4,6 has other targets involved in cell division. Here, we show that cyclin D-Cdk4,6 docks one side of an alpha-helix in the Rb C terminus, which is not recognized by cyclins E, A, and B. This helix-based docking mechanism is shared by the p107 and p130 Rb-family members across metazoans. Mutation of the Rb C-terminal helix prevents its phosphorylation, promotes G1 arrest, and enhances Rb's tumor suppressive function. Our work conclusively demonstrates that the cyclin D-Rb interaction drives cell division and expands the diversity of known cyclin-based protein docking mechanisms

Effect of unilateral training and bilateral training on physical performance: A meta-analysis

Background: In Unilateral (UNI) exercises are more effective than bilateral (BI) exercises in improving athletic performance is debatable.Objectives: this meta-analysis investigated the effects of UNI and BI exercises on different effect indicators of jump ability, sprint ability, maximal force, change of direction ability, and balance ability.Data Sources: PubMed, Google Scholar, Web of science, CNKI, Proquest, Wan Fang Data.Study Eligibility Criteria: To be eligible for inclusion in the meta-analysis, the study had to be: 1) athletes; 2) UNI training and BI training; 3) the intervention period had to be more than 6 weeks and the intervention frequency had to be more than 2 times/week; 4) the outcome indicators were jumping ability, sprinting ability, maximum strength, and change of direction and balance.Study Appraisal and Synthesis Method: We used the random-effects model for meta-analyses. Effect sizes (standardized mean difference), calculated from measures of horizontally oriented performance, were represented by the standardized mean difference and presented alongside 95% confidence intervals (CI).Results: A total of 28 papers met the inclusion criteria, and Meta-analysis showed that UNI training was more effective than BI training in improving jumping ability (ES = 0.61.0.23 to 0.09; Z = 3.12, p = 0.002 < 0.01), sprinting ability (ES = −0.02, −0.03 to −0.01; Z = 2.73, p = 0.006 < 0.01), maximum strength (ES = 8.95,2.30 to 15.61; Z = 2.64, p = 0.008 > 0.05), change of direction ability (ES = −0.03, −0.06 to 0.00; Z = 1.90, p = 0.06 > 0.01) and balance ability (ES = 1.41,-0.62 to 3.44; Z = 1.36, p = 0.17 > 0.01). The results of the analysis of moderating variables showed that intervention period, intervention frequency and intervention types all had different indicators of effect on exercise performance.Conclusion: UNI training has a more significant effect on jumping and strength quality for unilateral power patterns, and BI training has a more significant effect on jumping and strength quality for bilateral power patterns

PoxA, YjeK and Elongation Factor P Coordinately Modulate Virulence and Drug Resistance in \u3cem\u3eSalmonella enterica\u3c/em\u3e

We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-β-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, including attenuated virulence in mice, an increased ability to respire under nutrient-limiting conditions, hypersusceptibility to a variety of diverse growth inhibitors, and altered expression of multiple proteins, including several encoded on the SPI-1 pathogenicity island. PoxA mediates posttranslational modification of bacterial elongation factor P (EF-P), analogous to the modification of the eukaryotic EF-P homolog, eIF5A, with hypusine. The modification of EF-P is a mechanism of regulation whereby PoxA acts as an aminoacyl-tRNA synthetase that attaches an amino acid to a protein resembling tRNA rather than to a tRNA

RhoA GTPase inhibition organizes contraction during epithelial morphogenesis

During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination of cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit RhoA activity. Most studies of tissue folding, including apical constriction, have focused on how RhoA is activated by GEFs to promote cell contractility, with little investigation as to how GAPs may be important. Here, we identify a critical role for a RhoA GAP, Cumberland GAP (C-GAP), which coordinates with a RhoA GEF, RhoGEF2, to organize spatiotemporal contractility during Drosophila melanogaster apical constriction. C-GAP spatially restricts RhoA pathway activity to a central position in the apical cortex. RhoGEF2 pulses precede myosin, and C-GAP is required for pulsation, suggesting that contractile pulses result from RhoA activity cycling. Finally, C-GAP expression level influences the transition from reversible to irreversible cell shape change, which defines the onset of tissue shape change. Our data demonstrate that RhoA activity cycling and modulating the ratio of RhoGEF2 to C-GAP are required for tissue folding.American Cancer Society (125792-RSG-14-039-01-CSM

Loss of Gα12/13 exacerbates apical area dependence of actomyosin contractility

During development, coordinated cell shape changes alter tissue shape. In the Drosophila ventral furrow and other epithelia, apical constriction of hundreds of epithelial cells folds the tissue. Genes in the G[subscript α12/13] pathway coordinate collective apical constriction, but the mechanism of coordination is poorly understood. Coupling live-cell imaging with a computational approach to identify contractile events, we discovered that differences in constriction behavior are biased by initial cell shape. Disrupting G[subscript α12/13] exacerbates this relationship. Larger apical area is associated with delayed initiation of contractile pulses, lower apical E-cadherin and F-actin levels, and aberrantly mobile Rho-Kinase structures. Our results suggest that loss of G[subscript α12/13] disrupts apical actin cortex organization and pulse initiation in a size-dependent manner. We propose that G[subscript α12/13] robustly organizes the apical cortex despite variation in apical area to ensure the timely initiation of contractile pulses in a tissue with heterogeneity in starting cell shape

Coordination of cellular force-generation during Drosophila ventral furrow formation

Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2016.Cataloged from PDF version of thesis.Includes bibliographical references (pages 107-115).Spatiotemporally coordinated cell behavior is observed during morphogenesis, in both embryonic development as well as tissue regeneration. An open question is how individual cells collectively generate force to achieve the correct tissue architecture. This thesis examines how the apical forces generated by Drosophila ventral furrow cells undergoing collective apical constriction are coordinated to fold the tissue. In Chapter 2, I investigate how discrete actomyosin contraction events are coordinated in time and between neighboring cells to yield tissue contraction and folding. I developed a computational pipeline to identify and classify contraction events from live images of ventral furrow formation. Using this framework, I found heterogeneity in contraction events, both in terms of contraction intensity as well as apical area behavior. I found that apical constricting cells transition in contractile behavior over time, from undergoing reversible contractions into a ratcheted state where contractions are irreversible. High expression of the transcription factor Twist is required for the transition into this irreversible, ratcheted state, which is associated with more neighboring contractions as well as cooperative interactions between neighbors. In Chapter 3, I examined how contractility is buffered against heterogeneity in cell apical area. I found that Cta-signaling is required to robustly maintain apical Factin cortex that can support contracting over larger apical distances. Without this buffering, apically larger cells progressively lose apical F-actin and exhibit delayed initiation of actomyosin contractions, leading to a lack of coordinated constriction.by Shicong Xie.Ph. D

Thermodynamic analysis and experimental verification for silicon recovery from the diamond wire saw silicon powder by vacuum carbothermal reduction

Recovering silicon from waste material is profoundly significant in terms of making profit and encouraging development within the photovoltaic manufacturing industry. Eliminating oxygen is essential for the preparation of high purity silicon. However, a substantial amount of oxygen exists in diamond wire saw silicon powder (DWSSP), creating a barrier for the effective silicon recovery caused by a nonnegligible silicon loss. In this paper, amorphous silicon dioxide and the Si core - SiO2 shell structure was systematically characterized and confirmed. A thermodynamic calculation was then carried out to analyze the reduction reaction probability of silicon dioxide by vacuum carbothermal reduction. The results indicated that the reduction reaction could occur under the vacuum condition with lower temperature, while it could not under that of the atmospheric condition. Further, experiments were conducted to verify the reliability of the thermodynamic analysis, which are keeping in good agreement with thermodynamic results. Finally, the results confirmed that the vacuum carbothermal reduction method is a feasible alternative for silicon recovery from the DWSSP. This research provides contributions to understanding the recovery of silicon resources from DWSSP with the vacuum process, making it competitive with existing silicon recovery methods

Differences in urban heat island and its driving factors between central and new urban areas of Wuhan, China

Urban heat island (UHI) is one of the important effects of urbanization on built environment. Land surface temperature data was taken from moderate-resolution imaging spectroradiometer (MODIS) to investigate the long-term spatiotemporal patterns of UHI in Wuhan during 2001~2018 and, the UHI intensity changes of built-up land in 13 administrative regions in Wuhan were analyzed. Furthermore, 34 spatial error models and 34 ordinary least squares models were established and compared. Spatial error models showed good fitting effect, which were used to determine the influence of normalized difference vegetation index (NDVI), normalized difference building index (NDBI), and social–economic factors (population and nighttime light) on UHI intensity in central urban area and new urban area. The explanatory power changes of these four indicators during 2001~2018 were explored as well. The average UHI intensity in 2014~2018 has increased by about 0.45 °C compared to that in 2001~2005. NDBI is the most dominant factor contributing to the increase in temperature. The impact of NDVI on UHI intensity changes from negative to positive, and the impact of NDBI on UHI intensity in central urban area is weakened during 2001–2018. Social–economic factors have a greater impact on new urban area than on central urban area. These findings show the effects and the explanatory power changes of driving factors during 18 years, which can provide a better understanding of the formation and development of UHI and support for the future urban planning of Wuhan