Effects of thermal fluctuation and the receptor-receptor interaction in bacterial chemotactic signalling and adaptation

Bacterial chemotaxis is controlled by the conformational changes of the receptors, in response to the change of the ambient chemical concentration. In a statistical mechanical approach, the signalling due to the conformational changes is a thermodynamic average quantity, dependent on the temperature and the total energy of the system, including both ligand-receptor interaction and receptor-receptor interaction. This physical theory suggests to biology a new understanding of cooperation in ligand binding and receptor signalling problems. How much experimental support of this approach can be obtained from the currently available data? What are the parameter values? What is the practical information for experiments? Here we make comparisons between the theory and recent experimental results. Although currently comparisons can only be semi-quantitative or qualitative, consistency is clearly shown. The theory also helps to sort a variety of data.Comment: 26 pages, revtex. Journal version. Analysis on another set of data on adaptation time is adde

Synthesis, characterization and electrical properties of GO/PANI/NPs (NPs = CdSe, CdSe/CdS, CdSe/ZnS) nanocomposites

In this paper, GO/PANI/NPs (NPs = CdSe, CdSe/CdS, CdSe/ZnS) nanocomposites have been prepared using chemical method. The electrical properties of CdSe quantum dots, core shell nanoparticles (CdSe@CdS and CdSe@ZnS), graphene oxide/polyaniline nanocomposite (GO/PANI) and graphene oxide/polyaniline/nanoparticles (GO/PANI/NPs) nanocomposites have been measured using electrometer/high resistance meter (Keithley 6517A) at different wt% ratio. The above obtained nanoparticles (CdSe, CdSe@CdS and CdSe@ZnS) show the electrical current in nano ampere (nA) range while GO/PANI nanocomposites show the electrical current in miliampere (mA) range in the I-V measurement. The results of this study have been expected to reveal the effect of finite particle size on the conductivity of nanoparticles. The observed electrical conductivity of GO/PANI/NPs nanocomposites has been significantly reduced after the mixing of above obtained nanoparticles in different wt% ratio with GO/PANI nanocomposites. The knowledge of electrical conductivity and the effective mechanism for the conduction in nanocomposite is important for the fabrication of an electronic device such as solar cell

How does community context influence coalitions in the formation stage? a multiple case study based on the Community Coalition Action Theory

<p>Abstract</p> <p>Background</p> <p>Community coalitions are rooted in complex and dynamic community systems. Despite recognition that environmental factors affect coalition behavior, few studies have examined how community context impacts coalition formation. Using the Community Coalition Action theory as an organizing framework, the current study employs multiple case study methodology to examine how five domains of community context affect coalitions in the formation stage of coalition development. Domains are history of collaboration, geography, community demographics and economic conditions, community politics and history, and community norms and values.</p> <p>Methods</p> <p>Data were from 8 sites that participated in an evaluation of a healthy cities and communities initiative in California. Twenty-three focus groups were conducted with coalition members, and 76 semi-structured interviews were conducted with local coordinators and coalition leaders. Cross-site analyses were conducted to identify the ways contextual domains influenced selection of the lead agency, coalition membership, staffing and leadership, and coalition processes and structures.</p> <p>Results</p> <p>History of collaboration influenced all four coalition factors examined, from lead agency selection to coalition structure. Geography influenced coalition formation largely through membership and staffing, whereas the demographic and economic makeup of the community had an impact on coalition membership, staffing, and infrastructure for coalition processes. The influence of community politics, history, norms and values was most noticeable on coalition membership.</p> <p>Conclusions</p> <p>Findings contribute to an ecologic and theory-based understanding of the range of ways community context influences coalitions in their formative stage.</p

Loss of ARNT in skeletal muscle limits muscle regeneration in aging

The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23-25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2-3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle-specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT-deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle

Expression of the 60 kDa and 71 kDa heat shock proteins and presence of antibodies against the 71 kDa heat shock protein in pediatric patients with immune thrombocytopenic purpura

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against platelet proteins, particularly platelet glycoprotein IIb/IIIa. Heat shock proteins (Hsp) have been shown to be major antigenic determinants in some autoimmune diseases. Antibodies to Hsps have also been reported to be associated with a number of pathological states. METHODS: Using western blot, we measured the levels of the 60 kDa heat shock protein (Hsp60) and of the inducible 71 kDa member of the Hsp70 family (Hsp71) in lymphocytes and the presence of antibodies against these hsps in plasma of 29 pediatric patients with ITP before the treatment and in 6 other patients before and after treatment. RESULTS: Interestingly only one out of 29 patients showed detectable Hsp60 in lymphocytes while this heat shock protein was detected in the 30 control children. Hsp71 levels were slightly lower in lymphocytes of patients with ITP than in controls (1567.8 ± 753.2 via 1763.2 ± 641.8 integrated optical density (IOD) units). There was a small increase of Hsp71 after recovery from ITP. The titers of plasma antibodies against Hsp60 and Hsp71 were also examined. Antibodies against Hsp71 were more common in ITP patients (15/29) than in control children (5/30). The titer of anti-Hsp71 was also higher in children patients with ITP. The prevalence of ITP children with antibodies against Hsp71 (51.7%) was as high as those with antibodies against platelet membrane glycoproteins (58.3%). CONCLUSIONS: In summary, pediatric patients with ITP showed no detectable expression of Hsp60 in lymphocytes and a high prevalence of antibody against Hsp71 in plasma. These changes add to our understanding of the pathogenesis of ITP and may be important for the diagnosis, prognosis and treatment of ITP

Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains unknown, depletion of surface heparan sulfates block H522 infection. Temporally resolved transcriptomic and proteomic profiling reveal alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type I interferon signaling. These findings establish an alternative SARS-CoV-2 host cell receptor for the E484D SARS-CoV-2 variant, which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis

Diffusion of excellence: evaluating a system to identify, replicate, and spread promising innovative practices across the Veterans health administration

IntroductionThe Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program provides a system to identify, replicate, and spread promising practices across the largest integrated healthcare system in the United States. DoE identifies innovations that have been successfully implemented in the VHA through a Shark Tank style competition. VHA facility and regional directors bid resources needed to replicate promising practices. Winning facilities/regions receive external facilitation to aid in replication/implementation over the course of a year. DoE staff then support diffusion of successful practices across the nationwide VHA.MethodsOrganized around the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework, we summarize results of an ongoing long-term mixed-methods implementation evaluation of DoE. Data sources include: Shark Tank application and bid details, tracking practice adoptions through a Diffusion Marketplace, characteristics of VHA facilities, focus groups with Shark Tank bidders, structured observations of DoE events, surveys of DoE program participants, and semi-structured interviews of national VHA program office leaders, VHA healthcare system/facility executives, practice developers, implementation teams and facilitators.ResultsIn the first eight Shark Tanks (2016–2022), 3,280 Shark Tank applications were submitted; 88 were designated DoE Promising Practices (i.e., practices receive facilitated replication). DoE has effectively spread practices across the VHA, with 1,440 documented instances of adoption/replication of practices across the VHA. This includes 180 adoptions/replications in facilities located in rural areas. Leadership decisions to adopt innovations are often based on big picture considerations such as constituency support and linkage to organizational goals. DoE Promising Practices that have the greatest national spread have been successfully replicated at new sites during the facilitated replication process, have close partnerships with VHA national program offices, and tend to be less expensive to implement. Two indicators of sustainment indicate that 56 of the 88 Promising Practices are still being diffused across the VHA; 56% of facilities originally replicating the practices have sustained them, even up to 6 years after the first Shark Tank.ConclusionDoE has developed a sustainable process for the identification, replication, and spread of promising practices as part of a learning health system committed to providing equitable access to high quality care

The Use of Spinning-Disk Confocal Microscopy for the Intravital Analysis of Platelet Dynamics in Response to Systemic and Local Inflammation

Platelets are central players in inflammation and are an important component of the innate immune response. The ability to visualize platelets within the live host is essential to understanding their role in these processes. Past approaches have involved adoptive transfer of labelled platelets, non-specific dyes, or the use of fluorescent antibodies to tag platelets in vivo. Often, these techniques result in either the activation of the platelet, or blockade of specific platelet receptors. In this report, we describe two new methods for intravital visualization of platelet biology, intravenous administration of labelled anti-CD49b, which labels all platelets, and CD41-YFP transgenic mice, in which a percentage of platelets express YFP. Both approaches label endogenous platelets and allow for their visualization using spinning-disk confocal fluorescent microscopy. Following LPS-induced inflammation, we were able to measure a significant increase in both the number and size of platelet aggregates observed within the vasculature of a number of different tissues. Real-time observation of these platelet aggregates reveals them to be large, dynamic structures that are continually expanding and sloughing-off into circulation. Using these techniques, we describe for the first time, platelet recruitment to, and behaviour within numerous tissues of the mouse, both under control conditions and following LPS induced inflammation

Microscopy in forensic science

This chapter examines the use of electron microscopy, atomic force microscopy and other analytical techniques in forensic investigation and research. These tools can be used to enhance examination of human remains and trace evidence to improve understanding of cause of death, victim identification or post mortem interval.A police-designed scenario is used to highlight trace evidence such as glass, gun shot residue and paint. The validity of forensic techniques is discussed, with reference to international standards, repeatability, and false convictions. Ballistic evidence is used to highlight the complexities in evidence interpretation, including manufacturing variability, environmental effects and likelihood ratios.The use of scanning electron microscopy (SEM), atomic force microscopy (AFM) and other techniques in the development of forensic research is showcased, with particular examples from the field of fingerprints. Examples include improvements in the development of fingermarks from difficult surfaces, interaction of evidence types, and added intelligence from the crime scene, such as forensic timeline or gender of perpetrator

Estimation of stature from the foot and its segments in a sub-adult female population of North India

<p>Abstract</p> <p>Background</p> <p>Establishing personal identity is one of the main concerns in forensic investigations. Estimation of stature forms a basic domain of the investigation process in unknown and co-mingled human remains in forensic anthropology case work. The objective of the present study was to set up standards for estimation of stature from the foot and its segments in a sub-adult female population.</p> <p>Methods</p> <p>The sample for the study constituted 149 young females from the Northern part of India. The participants were aged between 13 and 18 years. Besides stature, seven anthropometric measurements that included length of the foot from each toe (T1, T2, T3, T4, and T5 respectively), foot breadth at ball (BBAL) and foot breadth at heel (BHEL) were measured on both feet in each participant using standard methods and techniques.</p> <p>Results</p> <p>The results indicated that statistically significant differences (p < 0.05) between left and right feet occur in both the foot breadth measurements (BBAL and BHEL). Foot length measurements (T1 to T5 lengths) did not show any statistically significant bilateral asymmetry. The correlation between stature and all the foot measurements was found to be positive and statistically significant (<it>p-value </it>< 0.001). Linear regression models and multiple regression models were derived for estimation of stature from the measurements of the foot. The present study indicates that anthropometric measurements of foot and its segments are valuable in the estimation of stature. Foot length measurements estimate stature with greater accuracy when compared to foot breadth measurements.</p> <p>Conclusions</p> <p>The present study concluded that foot measurements have a strong relationship with stature in the sub-adult female population of North India. Hence, the stature of an individual can be successfully estimated from the foot and its segments using different regression models derived in the study. The regression models derived in the study may be applied successfully for the estimation of stature in sub-adult females, whenever foot remains are brought for forensic examination. Stepwise multiple regression models tend to estimate stature more accurately than linear regression models in female sub-adults.</p