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Zn2+ ions are essential in many physiological processes, including enzyme catalysis, protein structural stabilization, and the regulation of many proteins. The affinities of proteins for Zn2+ ions span several orders of magnitude, with catalytic Zn2+ ions generally held more tightly than structural or regulatory ones. Metal carrier proteins, most of which are not specific for Zn2+, bind these ions with a broad range of affinities that overlap those of catalytic, structural, and regulatory Zn2+ ions and are thought to be responsible for distributing the metal through most cells, tissues, and fluid compartments. While little is known about how many proteins obtain or release these ions, there is now considerable experimental evidence suggesting that metal carrier proteins may be responsible for transferring metals to and from some Zn2+-dependent proteins, thus serving as a major regulatory factor for them. In this review, the biological roles of Zn2+ and structures of Zn2+ binding sites are examined, and experimental evidence demonstrating the direct participation of metal carrier proteins in enzyme regulation is discussed. Mechanisms of metal ion transfer are also offered, and the potential physiological significance of this phenomenon is explored.

Soil aeration is a crucial factor that regulates crop residue decomposition, and the chemical composition of decomposing crop residues may change the forms and availability of soil nutrients, such as N and P. However, to date, differences in the chemical composition of crop straw residues after incorporation into soil and during its decomposition under anaerobic vs. aerobic conditions have not been well documented. The objective of the present study was to assess changes in the C-containing functional groups of wheat straw residue during its decomposition in anaerobic and aerobic environments. A 12-month incubation experiment was carried out to investigate the temporal variations of mass, carbon, and nitrogen loss, as well as changes in the chemical composition of wheat (Triticum aestivum L) straw residues under anaerobic and aerobic conditions by measuring C-containing functional groups using solid state nuclear magnetic resonance (NMR) spectroscopy. The residual mass, carbon content, and nitrogen content of the straw residue sharply declined during the initial 3 months, and then slowly decreased during the last incubation period from 3 to 12 months. The decomposition rate constant (k) for mass loss under aerobic conditions (0.022 d-1) was higher than that under anaerobic conditions (0.014 d-1). The residual mass percentage of cellulose and hemicellulose in the wheat straw gradually declined, whereas that of lignin gradually increased during the entire 12-month incubation period. The NMR spectra of C-containing functional groups in the decomposing straw under both aerobic and anaerobic conditions were similar at the beginning of the incubation as well as at 1 month, 6 months, and 12 months. The main alterations in C-containing functional groups during the decomposition of wheat straw were a decrease in the relative abundances of O-alkyl C and an increase in the relative abundances of alkyl C, aromatic C and COO/N-C = O functional groups. The NMR signals of alkyl C and aromatic C in decomposing wheat straw residues under anaerobic condition were higher than those under aerobic conditions. The higher mass percentages of lignin and the higher signals of aromatic C and alkyl C functional groups in decomposing wheat residues under anaerobic conditions than under aerobic conditions were due to the slower decomposition rates of aryl C and alkyl C in wheat straw residues under anaerobic conditions.

In this new work, political theorist Michael J. Thompson argues that modern societies are witnessing a decline in one of the core building blocks of modernity: the autonomous self. Far from being an illusion of the Enlightenment, Thompson contends that the individual is a defining feature of the project to build a modern democratic culture and polity. One of the central reasons for its demise in recent decades has been the emergence of what he calls the \"cybernetic society,\" a cohesive totalization of the social logics of the institutional spheres of economy, culture and polity. These logics have been progressively defined by the imperatives of economic growth and technical-administrative management of labor and consumption, routinizing patterns of life, practices, and consciousness throughout the culture. Evolving out of the neoliberal transformation of economy and society since the 1980s, the cybernetic society has transformed how that the individual is articulated in contemporary society. Thompson examines the various pathologies of the self and consciousness that result from this form of socialization—such as hyper-reification, alienated moral cognition, false consciousness, and the withered ego—in new ways to demonstrate the extent of deformation of modern selfhood. Only with a more robust, more socially embedded concept of autonomy as critical agency can we begin to reconstruct the principles of democratic individuality and community.

For God and Globerecovers the history of an important yet largely forgotten intellectual movement in interwar America. Michael G. Thompson explores the way radical-left and ecumenical Protestant internationalists articulated new understandings of the ethics of international relations between the 1920s and the 1940s. Missionary leaders such as Sherwood Eddy and journalists such as Kirby Page, as well as realist theologians including Reinhold Niebuhr, developed new kinds of religious enterprises devoted to producing knowledge on international relations for public consumption.For God and Globecenters on the excavation of two such efforts-the leading left-wing Protestant interwar periodical,The World Tomorrow, and the landmark Oxford 1937 ecumenical world conference. Thompson charts the simultaneous peak and decline of the movement in John Foster Dulles's ambitious efforts to link Christian internationalism to the cause of international organization after World War II. Concerned with far more than foreign policy, Christian internationalists developed critiques of racism, imperialism, and nationalism in world affairs. They rejected exceptionalist frameworks and eschewed the dominant \"Christian nation\" imaginary as a lens through which to view U.S. foreign relations. In the intellectual history of religion and American foreign relations, Protestantism most commonly appears as an ideological ancillary to expansionism and nationalism.For God and Globechallenges this account by recovering a movement that held Christian universalism to be a check against nationalism rather than a boon to it.

Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures up to 36k CpGs per species that are well conserved across many mammalian species. We designed a set of probes that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development of epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others. Methods to probe DNA methylation in the majority of non-human mammals are lacking. Here the authors developed a Mammalian Methylation Array that includes 36k well-conserved CpGs in mammals which will facilitate cross-species comparisons. They annotate the conserved CpGs in > 200 species. The array allows one to measure methylation in all mammalian species including unsequenced ones.

Aortic stenosis (AS) is one of the most common heart valve conditions and its incidence and prevalence increases with age. With the introduction of transcatheter aortic valve replacement (TAVR), racial and ethnic disparities in AS diagnosis, treatment and outcomes is poorly understood. In this study we assessed racial and ethnic disparities in AS diagnosis, treatment, and outcomes among Medicare beneficiaries. We conducted a population-based cohort study of inpatient, outpatient, and professional claims from a 20% sample of Medicare beneficiaries. Incidence and Prevalence was determined among Medicare Beneficiaries. Outcomes in this study included management; the number of (non)-interventional cardiology and cardiothoracic surgery evaluation and management (E&M) visits, and number of transthoracic echocardiograms (TTE) performed. Treatment, which was defined as Surgical Aortic Valve Replacement and Transthoracic Aortic Valve Replacement. And outcomes described as All-cause Hospitalizations, Heart Failure Hospitalization and 1-year mortality. A total of 1,513,455 Medicare beneficiaries were diagnosed with AS (91.3% White, 4.5% Black, 1.1% Hispanic, 3.1% Asian and North American Native) between 2010 and 2018. Annual prevalence of AS diagnosis was lower for racial and ethnic minorities compared with White patients, with adjusted rate ratios of 0.66 (95% CI 0.65 to 0.68) for Black patients, 0.67 (95% CI 0.64 to 0.70) for Hispanic patients and 0.75 (95% CI 0.73 to 0.77) for Asian and North American Native patients as recent as 2018. After adjusting for age, sex and comorbidities, cardiothoracic surgery E&M visits and treatment rates were significantly lower for Black, Hispanic and Asian and North American Native patients compared with White patients. All-cause hospitalization rate was higher for Black and Hispanic patients compared with White patient. 1-year mortality was higher for Black patients, while Hispanic and Asian and North American Native patients had lower 1-year mortality compared with White patients. We demonstrated significant racial and ethnic disparities in the diagnosis, management and outcomes of AS. The factors driving the persistence of these disparities in AS care need to be elucidated to develop an equitable health care system.

In 1988, James Coleman observed that “social capital is defined by its function. It is not a single entity but a variety of different entities, with two elements in common: they all consist of some aspect of social structures, and they facilitate certain actions of actors-whether persons or corporate actors-within the structure.” If one looks at the state of social capital research, it is clear that this is truer than ever before. This paper seeks to help researchers overcome the major challenges of social capital research, namely, measuring a concept that is notoriously difficult for measurement and choosing among the exhaustive list of direct, casual and consequential measures. It does so by arguing for a typology of social capital that considers five major types of social capital and then reviewing a diverse selection of data available from national surveys. This provides a resource for scholars wishing to pursue large-scale social capital research. Additionally, it draws six lessons from this body of theory and measurement to improve the study of social capital.

The creation of artificial enzymes is a key objective of computational protein design. Although de novo enzymes have been successfully designed, these exhibit low catalytic efficiencies, requiring directed evolution to improve activity. Here, we use room-temperature X-ray crystallography to study changes in the conformational ensemble during evolution of the designed Kemp eliminase HG3 ( k cat / K M 146 M −1 s −1 ). We observe that catalytic residues are increasingly rigidified, the active site becomes better pre-organized, and its entrance is widened. Based on these observations, we engineer HG4, an efficient biocatalyst ( k cat / K M 103,000 M −1 s −1 ) containing key first and second-shell mutations found during evolution. HG4 structures reveal that its active site is pre-organized and rigidified for efficient catalysis. Our results show how directed evolution circumvents challenges inherent to enzyme design by shifting conformational ensembles to favor catalytically-productive sub-states, and suggest improvements to the design methodology that incorporate ensemble modeling of crystallographic data. Kemp eliminases are artificial enzymes that catalyze the concerted deprotonation and ring-opening of benzisoxazoles. Here, the authors use room-temperature X-ray crystallography to investigate changes to the conformational ensemble of the Kemp eliminase HG3 along a directed evolutionary trajectory, and develop an experimentally guided, ensemble-based computational enzyme design procedure.

DNA methylation is an epigenetic mark associated with regulation of transcription and genome structure. These markers have been investigated in a variety of cancer settings for their utility in differentiating normal tissue from tumor tissue. Here, we examine the direct correlation between DNA methylation and patient survival. We find that changes in the DNA methylation of key pancreatic developmental genes are strongly associated with patient survival.

The nonlinear axisymmetric post-buckling behaviour of perfect, thin, elastic spherical shells subject to external pressure and their asymmetric bifurcations are characterized, providing results for a structure/loading combination with an exceptionally nonlinear buckling response. Immediately after the onset of buckling, the buckling mode localizes into a dimple at the poles. The relations among the pressure, the dimple amplitude and the change in volume of the shell are determined over a large range of pole deflections. These results allow accurate evaluation of criteria such as the Maxwell condition for which the energies in the unbuckled and buckled states are the same and evaluation of the influences of pressure versus volume-controlled loadings. Non-axisymmetric bifurcation from the axisymmetric state, which occurs deep into the post-buckling regime in the form of multi-lobed dimples, is also established and discussed. This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’