Genetic and Molecular Characterization of Flagellar Assembly in Shewanella oneidensis

Shewanella oneidensis is a highly motile organism by virtue of a polar flagellum. Unlike most flagellated bacteria, it contains only one major chromosome segment encoding the components of the flagellum with the exception of the motor proteins. In this region, three genes encode flagellinsaccording to the original genome annotation. However, we find that only flaA and flaB encode functional filament subunits. Although these two genesare under the control of different promoters, they are actively transcribed and subsequently translated, producing a considerable number of flagellin proteins. Additionally, both flagellins are able to interact with their chaperon FliS and are subjected to feedback regulation. Furthermore, FlaA and FlaB are glycosylated by a pathwayinvolving a major glycosylating enzyme,PseB, in spite of the lack of the majority of theconsensus glycosylation sites. In conclusion, flagellar assembly in S. oneidensis has novel features despite the conservation of homologous genes across taxa

Sandpile-simulation-based graph data model for MVD generative design of shield tunnel lining using information entropy

BIM standard development is central to the performance and behavior of BIM model application across transmission, visualization, and information management perspectives. Tremendous effort has been made to ease the implementation of IFC data model in practice. Yet, the complexity of IFC data model hurdles the implementation of the import and export functionality by software vendors. To overcome this, buildingSMART introduced the concept of Model View Definitions to define which parts of an IFC data model need to be implemented for a specific data exchange scenario. With such, the certification of compatibility for software products with the IFC standard is formed. The Model View Definition is use case orientated to determine whether the specific information should be included in an IFC partial model. With the creation of ad-hoc, project-specific Exchange Requirements increasing, associated MVD development requires much more work to incorporate standard development. To resolve this issue, this paper attempts to exploit the potential of information entropy which has proven itself extremely crucial in many other industries in terms of information management, and then integrates it with sandpile simulation to propose a Top-down hierarchy to structure as well as interpret IFC partial model via Model View Definition. The proposed information entropy shifted MVD development approach would manage to unify the MVD development process that enables the reduction on confusion for various end users, specific organization, or project needs. Moreover, to better translate the BIM standard topology into sandpile simulations, a new notion system is proposed. Sandpile simulations are further implemented to prove their applicability, during the simulation, self-organized criticality is identified, and the existence of chaos is observed

Network structure of emotional and behavioral problems, loneliness, and suicidal thoughts in adolescents at the school closure and reopening stage in China

BACKGROUND: Public restriction and school closure policies during the pandemic may have long-term effects on adolescents' mental health, and adolescents' feelings and needs may change as the pandemic progresses. This study was conducted to explore the network structure and differences in emotional and behavioral problems (EBPs), loneliness, and suicidal thoughts in adolescents during different pandemic periods in China. METHODS: Based on two cross-sectional studies conducted in Taizhou, China, during school closure (April 16 to May 14, 2020) and reopening (May 25 to July 10, 2021) using online questionnaire, a total of 14,726 adolescents (school closure: 6,587, school reopening: 8,139) were recruited. EBPs were evaluated based on the student version of the Strengths and Difficulties Questionnaire (SDQ). Loneliness and suicidal thoughts were measured by item 20 and item 9 of the Chinese version of the Children's Depression Inventory (CDI), respectively. Network analysis was used to estimate the network connections and properties between EBPs, loneliness, and suicidal thoughts. RESULTS: The prevalence of psychosocial problems significantly increased at the school reopening compared with the school closure: EBPs: 36.8% vs. 31.6%; loneliness: 40.3% vs. 33.9%; suicidal thoughts: 40.8% vs. 15.4%. Suicidal thoughts showed the closest connections with being unhappy and lonely. Being bullied was strongly connected with conduct problems of lying and stealing. The links between hyperactivity symptoms and the other domains of EBPs were stronger after the school reopened. Being unhappy and showing the hyperactivity symptoms of "nonpersistent, distractible, and fidgety" presented high network and bridge (increasing transference from one symptom domain to another) centrality. Loneliness showed high expected influence and bridge centrality. CONCLUSIONS: This study highlighted the high prevalence of EBPs, loneliness, and suicidal thoughts in Chinese adolescents. It also presented the network structure of these psychological problems over different pandemic stages. It is recommended that psychological support should be provided for adolescents, especially focusing on the central and bridge symptoms highlighted in this study

The roles of leader empowering behaviour and employee proactivity in daily job crafting: a compensatory Model

The study investigates how daily fluctuations in leader self-rated empowering behaviour are related to employees’ daily level job crafting behaviour. From an interactionist perspective, the authors propose and test two competing theoretical models investigating how supervisors’ daily empowering behaviour and subordinates’ proactive personality jointly affect subordinates’ daily work engagement and daily job crafting. One hundred and six leader-follower dyads working in several companies completed a questionnaire and a diary booklet over five consecutive workdays. The results of multi-level analyses revealed a cross-level-moderated mediation model, of which the indirect effect of empowering behaviour on job crafting via work engagement was stronger for less proactive employees than for higher proactive employees. The findings reveal a compensatory relation between leader empowering behaviour and employee proactive personality, suggesting that empowering behaviour would be more effective for increasing the work engagement of less proactive workers. Future directions and human resource management implications are discusse

A California Statewide Three-Dimensional Seismic Velocity Model from Both Absolute and Differential Times

We obtain a seismic velocity model of the California crust and uppermost mantle using a regional-scale double-difference tomography algorithm. We begin by using absolute arrival-time picks to solve for a coarse three-dimensional (3D) P velocity (V_P) model with a uniform 30 km horizontal node spacing, which we then use as the starting model for a finer-scale inversion using double-difference tomography applied to absolute and differential pick times. For computational reasons, we split the state into 5 subregions with a grid spacing of 10 to 20 km and assemble our final statewide V_P model by stitching together these local models. We also solve for a statewide S-wave model using S picks from both the Southern California Seismic Network and USArray, assuming a starting model based on the VP results and a V_P/V_S ratio of 1.732. Our new model has improved areal coverage compared with previous models, extending 570 km in the SW–NE direction and 1320 km in the NW–SE direction. It also extends to greater depth due to the inclusion of substantial data at large epicentral distances. Our V_P model generally agrees with previous separate regional models for northern and southern California, but we also observe some new features, such as high-velocity anomalies at shallow depths in the Klamath Mountains and Mount Shasta area, somewhat slow velocities in the northern Coast Ranges, and slow anomalies beneath the Sierra Nevada at midcrustal and greater depths. This model can be applied to a variety of regional-scale studies in California, such as developing a unified statewide earthquake location catalog and performing regional waveform modeling

Polyploids require Bik1 for kinetochore–microtubule attachment

The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data is presented demonstrating that the budding yeast CLIP-170 orthologue Bik1is a component of the kinetochore-MT binding interface. Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids. The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton. In polyploid cells, Bik1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids. The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics. The finding that a protein involved in kinetochore–MT attachment is required for the viability of polyploids has potential implications for cancer therapeutics

Low-Dose Recombinant Adeno-Associated Virus-Mediated Inhibition of Vascular Endothelial Growth Factor Can Treat Neovascular Pathologies Without Inducing Retinal Vasculitis

The wet form of age-related macular degeneration is characterized by neovascular pathologies that, if untreated, can result in edemas followed by rapid vision loss. Inhibition of vascular endothelial growth factor (VEGF) has been used to successfully treat neovascular pathologies of the eye. Nonetheless, some patients require frequent intravitreal injections of anti-VEGF drugs, increasing the burden and risk of complications from the procedure to affected individuals. Recombinant adeno-associated virus (rAAV)-mediated expression of anti-VEGF proteins is an attractive alternative to reduce risk and burden to patients. However, controversy remains as to the safety of prolonged VEGF inhibition in the eye. Here, we show that two out of four rAAV serotypes tested by intravitreal delivery to express the anti-VEGF drug conbercept lead to a dose-dependent vascular sheathing pathology that is characterized by immune cell infiltrates, reminiscent of vasculitis in humans. We show that this pathology is accompanied by increased expression in vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1), both of which promote extravasation of immune cells from the vasculature. While formation of the vascular sheathing pathology is prevented in immunodeficient Rag-1 mice that lack B and T cells, increased expression of VACM1 and ICAM1 still occurs, indicating that inhibition of VEGF function leads to expression changes in cell adhesion molecules that promote extravasation of immune cells. Importantly, a 10-fold lower dose of one of the vectors that cause a vascular sheathing pathology is still able to reduce edemas resulting from choroidal neovascularization without causing any vascular sheathing pathology and only a minimal increase in VCAM1 expression. The data suggest that treatments of neovascular eye pathologies with rAAV-mediated expression of anti VEGF drugs can be developed safely. However, viral load needs to be adjusted to the tropisms of the serotype and the expression pattern of the promoter

Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA-DNA pairing

Proper chromosome alignment and segregation during mitosis depend on cohesion between sister chromatids. Cohesion is thought to occur through the entrapment of DNA within the tripartite ring (Smc1, Smc3 and Rad21) with enforcement from a fourth subunit (SA1/SA2). Surprisingly, cohesin rings do not play a major role in sister telomere cohesion. Instead, this role is replaced by SA1 and telomere binding proteins (TRF1 and TIN2). Neither the DNA binding property of SA1 nor this unique telomere cohesion mechanism is understood. Here, using single-molecule fluorescence imaging, we discover that SA1 displays two-state binding on DNA: searching by one-dimensional (1D) free diffusion versus recognition through subdiffusive sliding at telomeric regions. The AT-hook motif in SA1 plays dual roles in modulating non-specific DNA binding and subdiffusive dynamics over telomeric regions. TRF1 tethers SA1 within telomeric regions that SA1 transiently interacts with. SA1 and TRF1 together form longer DNA-DNA pairing tracts than with TRF1 alone, as revealed by atomic force microscopy imaging. These results suggest that at telomeres cohesion relies on the molecular interplay between TRF1 and SA1 to promote DNA-DNA pairing, while along chromosomal arms the core cohesin assembly might also depend on SA1 1D diffusion on DNA and sequence-specific DNA binding

Loneliness and depressive symptoms among men who have sex with men in China: A cross-sectional study

BackgroundWhile psychosocial problems and their related factors in men who have sex with men (MSM) have been well documented in developed countries, there are still not many studies addressing this issue in China and the results are inconsistent. This study aimed to assess the prevalence of loneliness and depressive symptoms among MSM, examine their associated factors, and investigate potential factors moderating the link between depressive symptoms and loneliness.MethodsA cross-sectional study was conducted in Taizhou of Zhejiang Province in China between April and November 2021. Loneliness was assessed using the 3-item UCLA Loneliness Scale (UCLA-3), and depressive symptoms were measured using the Patient Health Questionaire-9 (PHQ-9). Data from 655 MSM were eligible for analysis. Logistic regression models were used to examine the associations between independent variables and the outcomes of loneliness and depression. The interaction terms were added in the models to assess the moderating effects.ResultsOf the MSM sample, 13.28 and 7.48% perceived loneliness and reported moderate-to-severe depressive symptoms, respectively. We found that participants who experienced loneliness were more likely to have younger age (OR 0.44, 95% CI 0.21, 0.93, 15–32 years as reference group), low social support (OR 3.60, 95% CI 2.14, 6.04), low self-esteem (OR 3.03, 95% CI 1.45, 6.32) and moderate-to-severe depressive symptoms (OR 5.45, 95% CI 2.66, 11.15). The participants with moderate-to-severe depressive symptoms were more likely to have low self-esteem (OR 6.78, 95% CI 3.08, 14.95) and feelings of loneliness (OR 5.51, 95% CI 2.66, 11.40). Stratified analyzes showed that the magnitude of the associations between depressive symptoms and loneliness varied in MSM with different age, marital status, and self-esteem.ConclusionOur study suggests that we need to pay attention to feelings of loneliness and depressive symptoms and their closely associated factors such as social support and self-esteem among MSM in China. The MSM who were young, not married, and had low self-esteem were especially vulnerable to the impact of depressive symptoms on loneliness

Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory Response in Human Retinal Pigment Epithelial Cells

Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD