Many bacterial species possess long filamentous structures known as pili or fimbriae extending from their surfaces. Despite the diversity in pilus structure and biogenesis, pili in Gram-negative ...bacteria are typically formed by non-covalent homopolymerization of major pilus subunit proteins (pilins), which generates the pilus shaft. Additional pilins may be added to the fiber and often function as host cell adhesins. Some pili are also involved in biofilm formation, phage transduction, DNA uptake and a special form of bacterial cell movement, known as 'twitching motility'. In contrast, the more recently discovered pili in Gram-positive bacteria are formed by covalent polymerization of pilin subunits in a process that requires a dedicated sortase enzyme. Minor pilins are added to the fiber and play a major role in host cell colonization.This review gives an overview of the structure, assembly and function of the best-characterized pili of both Gram-negative and Gram-positive bacteria.
The twenty-first century has witnessed a wave of severe infectious disease outbreaks, not least the COVID-19 pandemic, which has had a devastating impact on lives and livelihoods around the globe. ...The 2003 severe acute respiratory syndrome coronavirus outbreak, the 2009 swine flu pandemic, the 2012 Middle East respiratory syndrome coronavirus outbreak, the 2013-2016 Ebola virus disease epidemic in West Africa and the 2015 Zika virus disease epidemic all resulted in substantial morbidity and mortality while spreading across borders to infect people in multiple countries. At the same time, the past few decades have ushered in an unprecedented era of technological, demographic and climatic change: airline flights have doubled since 2000, since 2007 more people live in urban areas than rural areas, population numbers continue to climb and climate change presents an escalating threat to society. In this Review, we consider the extent to which these recent global changes have increased the risk of infectious disease outbreaks, even as improved sanitation and access to health care have resulted in considerable progress worldwide.
Cell competition was described in Drosophila as the loss from mosaic tissues of otherwise viable cells heterozygous for Ribosomal protein mutations (‘ Minutes ’). Cell competition has now been ...described to occur between multiple other genotypes, such as cells differing in myc expression levels, or mutated for neoplastic tumor suppressors. Recent studies implicate innate immunity components, and possibly mechanical stress, compression and cell intercalation as a consequence of differential growth rates in competitive cell death. Competition to eliminate pre-neoplastic tumors makes use of signals and receptors also used in patterning the nervous system including Slit/Robo2 and Sas/PTP10D to recognize and extrude clones of mutant cells, at least where local epithelial cyto-architecture is favorable. Cell competition facilitates expansion of Drosophila tumors through host tissue, and in normal development may promote developmental robustness and longevity by selecting for optimal progenitor cells.
Nonpharmaceutical interventions (NPIs) have been employed to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet these measures are already having similar ...effects on other directly transmitted, endemic diseases. Disruptions to the seasonal transmission patterns of these diseases may have consequences for the timing and severity of future outbreaks. Here we consider the implications of SARS-CoV-2 NPIs for two endemic infections circulating in the United States of America: respiratory syncytial virus (RSV) and seasonal influenza. Using laboratory surveillance data from 2020, we estimate that RSV transmission declined by at least 20% in the United States at the start of the NPI period. We simulate future trajectories of both RSV and influenza, using an epidemic model. As susceptibility increases over the NPI period, we find that substantial outbreaks of RSV may occur in future years, with peak outbreaks likely occurring in the winter of 2021–2022. Longer NPIs, in general, lead to larger future outbreaks although they may display complex interactions with baseline seasonality. Results for influenza broadly echo this picture, but are more uncertain; future outbreaks are likely dependent on the transmissibility and evolutionary dynamics of circulating strains.
Abstract
As Nature’s version of machine learning, evolution has solved many extraordinarily complex problems, none perhaps more remarkable than learning to harness an increase in chemical entropy ...(disorder) to generate directed chemical forces (order). Using muscle as a model system, here I describe the basic mechanism by which life creates order from disorder. In short, evolution tuned the physical properties of certain proteins to contain changes in chemical entropy. As it happens these are the “sensible” properties Gibbs postulated were needed to solve a paradox that has intrigued and challenged scientists and philosophers for over 100 years.
This book explains how True Cost Accounting is an effective tool we can use to address the pervasive imbalance in our food system. Calls are coming from all quarters that the food system is broken ...and needs a radical transformation. A system that feeds many yet continues to create both extreme hunger and diet-related diseases, and one which has significant environmental impacts, is not serving the world adequately. This volume argues that True Cost Accounting in our food system can create a framework for a systemic shift. What sounds on the surface like a practice relegated to accountants is ultimately a call for a new lens on the valuation of food and a new relationship with the food we eat, starting with the reform of a system out of balance. From the true cost of corn, rice and water, to incentives for soil health, the chapters economically compare conventional and regenerative, more equitable farming practices in and food system structures, including taking an unflinching look at the true cost of cheap labour. Overall, this volume points towards the potential for our food system to be more human-centred than profit-centred and one that has a more respectful relationship to the planet. It sets forth a path forward based on True Cost Accounting for food. This path seeks to fix our current food metrics, in policy and in practice, by applying a holistic lens that evaluates the actual costs and benefits of different food systems, and the impacts and dependencies between natural systems, human systems, agriculture and food systems. This volume is essential reading for professionals and policymakers involved in developing and reforming the food system, as well as students and scholars working on food policy, food systems and sustainability.
Preliminary evidence suggests that climate may modulate the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet it remains unclear whether seasonal and geographic ...variations in climate can substantially alter the pandemic trajectory, given that high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic by probing different scenarios based on known coronavirus biology. We find that although variations in weather may be important for endemic infections, during the pandemic stage of an emerging pathogen, the climate drives only modest changes to pandemic size. A preliminary analysis of nonpharmaceutical control measures indicates that they may moderate the pandemic-climate interaction through susceptible depletion. Our findings suggest that without effective control measures, strong outbreaks are likely in more humid climates and summer weather will not substantially limit pandemic growth.
The basic Helix-Loop-Helix (bHLH) proteins represent a well-known class of transcriptional regulators. Many bHLH proteins act as heterodimers with members of a class of ubiquitous partners, the E ...proteins. A widely expressed class of inhibitory heterodimer partners—the Inhibitor of DNA-binding (ID) proteins—also exists. Genetic and molecular analyses in humans and in knockout mice implicate E proteins and ID proteins in a wide variety of diseases, belying the notion that they are non-specific partner proteins. Here, we explore relationships of E proteins and ID proteins to a variety of disease processes and highlight gaps in knowledge of disease mechanisms.
The basic Helix-Loop-Helix (bHLH) proteins are well-known transcriptional regulators that heterodimerize with E proteins and can also partner with Inhibitor of DNA-binding (ID) proteins. Wang and Baker explore the relationships of E proteins and ID proteins to a variety of disease processes, which belies the notion that they are non-specific partner proteins.
Engineered hydrogels have been extensively used to direct cell function in 3D cell culture models, which are more representative of the native cellular microenvironment than conventional 2D cell ...culture. Previously, hyaluronan-furan and bis-maleimide polyethylene glycol hydrogels were synthesized via Diels–Alder chemistry at acidic pH, which did not allow encapsulation of viable cells. In order to enable gelation at physiological pH, the reaction kinetics were accelerated by replacing the hyaluronan-furan with the more electron-rich hyaluronan-methylfuran. These new click-cross-linked hydrogels gel faster and at physiological pH, enabling encapsulation of viable cells, as demonstrated with 3D culture of 5 different cancer cell lines. The methylfuran accelerates Diels–Alder cycloaddition yet also increases the retro Diels–Alder reaction. Using computational analysis, we gain insight into the mechanism of the increased Diels–Alder reactivity and uncover that transition state geometry and an unexpected hydrogen-bonding interaction are important contributors to the observed rate enhancement. This cross-linking strategy serves as a platform for bioconjugation and hydrogel synthesis for use in 3D cell culture and tissue engineering.
Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and ...their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes were differentiated by taste and smell sensitivity and movement-related sensory behavior. Further, sensory processing subtypes predicted communication competence and maladaptive behavior. The findings of this study lay the foundation for the generation of more specific hypotheses regarding the mechanisms of sensory processing dysfunction in autism, and support the continued use of sensory-based interventions in the remediation of communication and behavioral difficulties in autism.
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