Search

Atomic force microscopes (AFMs) have emerged as the principal enabling tool for nanotechnology research. They are used ubiquitously in a wide range of fields: from 2D materials, semiconductors, ferroelectrics, and batteries to biomolecules, polymers, and cell biology. As the name implies, AFMs are microscopes. However, rather than using focused light or electrons to magnify sample features, AFMs scan a mechanical probe with a very sharp tip over the surface to create a high-resolution 3D topographical image. Further, by modifying the probe composition or structure, other material properties (electrical, mechanical, magnetic, etc.) can be simultaneously measured and mapped onto the topographic image for precise structure/property correlation. Clearly, the probe is key to unlocking the power of the AFM, thus, choosing the right probe is critical. In this article, we will provide novice and experienced users with basic information and guidelines to simplify the AFM probe selection process. [ABSTRACT FROM AUTHOR]

Key Points: Question: What is the prevalence, penetrance, and expressivity of UBA1 variants in a health care system cohort? Findings: In this retrospective observational study of 163 096 participants, 11 individuals (1 in 13 591) harbored a UBA1 disease-causing variant and all participants had hematologic features along with a broad spectrum of autoimmune, pulmonary, and dermatologic clinical manifestations. Meaning: This study provides an estimate of the prevalence and a description of the clinical manifestations of VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome, although additional studies are needed in unselected and genetically diverse populations to better define general population prevalence and phenotypic spectrum. Importance: VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a disease with rheumatologic and hematologic features caused by somatic variants in UBA1. Pathogenic variants are associated with a broad spectrum of clinical manifestations. Knowledge of prevalence, penetrance, and clinical characteristics of this disease have been limited by ascertainment biases based on known phenotypes. Objective: To determine the prevalence of pathogenic variants in UBA1 and associated clinical manifestations in an unselected population using a genomic ascertainment approach. Design, Setting, and Participants: This retrospective observational study evaluated UBA1 variants in exome data from 163 096 participants within the Geisinger MyCode Community Health Initiative. Clinical phenotypes were determined from Geisinger electronic health record data from January 1, 1996, to January 1, 2022. Exposures: Exome sequencing was performed. Main Outcomes and Measures: Outcome measures included prevalence of somatic UBA1 variation; presence of rheumatologic, hematologic, pulmonary, dermatologic, and other findings in individuals with somatic UBA1 variation on review of the electronic health record; review of laboratory data; bone marrow biopsy pathology analysis; and in vitro enzymatic assays. Results: In 163 096 participants (mean age, 52.8 years; 94% White; 61% women), 11 individuals harbored likely somatic variants at known pathogenic UBA1 positions, with 11 of 11 (100%) having clinical manifestations consistent with VEXAS syndrome (9 male, 2 female). A total of 5 of 11 individuals (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS syndrome; however, all individuals had anemia (hemoglobin: mean, 7.8 g/dL; median, 7.5 g/dL), which was mostly macrocytic (10/11 [91%]) with concomitant thrombocytopenia (10/11 [91%]). Among the 11 patients identified, there was a pathogenic variant in 1 male participant prior to onset of VEXAS-related signs or symptoms and 2 female participants had disease with heterozygous variants. A previously unreported UBA1 variant (c.1861A>T; p.Ser621Cys) was found in a symptomatic patient, with in vitro data supporting a catalytic defect and pathogenicity. Together, disease-causing UBA1 variants were found in 1 in 13 591 unrelated individuals (95% CI, 1:7775-1:23 758), 1 in 4269 men older than 50 years (95% CI, 1:2319-1:7859), and 1 in 26 238 women older than 50 years (95% CI, 1:7196-1:147 669). Conclusions and Relevance: This study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US. Additional studies are needed in unselected and genetically diverse populations to better define general population prevalence and phenotypic spectrum. This retrospective observational study evaluates UBA1 variants in exome data from individuals in the Geisinger MyCode Community Health Initiative. [ABSTRACT FROM AUTHOR]

The article offers information about the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome and disease taxonomy in rheumatology. It mentions that VEXAS syndrome, discovered through the use of a genotype-first approach, whereby a large genetic database was analyzed for commonalities among patients, with minimal consideration of clinical phenotype.

Ubiquitylation is an essential post-translational modification that regulates intracellular signalling networks by triggering proteasomal substrate degradation, changing the activity of substrates or mediating changes in proteins that interact with substrates. Hundreds of enzymes participate in reversible ubiquitylation of proteins, some acting globally and others targeting specific proteins. Ubiquitylation is essential for innate immune responses, as it facilitates rapid regulation of inflammatory pathways, thereby ensuring sufficient but not excessive responses. A growing number of inborn errors of immunity are attributed to dysregulated ubiquitylation. These genetic disorders exhibit broad clinical manifestations, ranging from susceptibility to infection to autoinflammatory and/or autoimmune features, lymphoproliferation and propensity to malignancy. Many autoinflammatory disorders result from disruption of components of the ubiquitylation machinery and lead to overactivation of innate immune cells. An understanding of the disorders of ubiquitylation in autoinflammatory diseases could enable the development of novel management strategies. [ABSTRACT FROM AUTHOR]

The article focuses on the decision of the U.S. Supreme Court in the case Fulton v. City of Philadelphia wherein Catholic organization sought a religious exception from the City of Philadelphia in response to the City's antidiscrimination policies, claiming that compliance with the policies would make the organization endorse same-sex relationship. It mentions protection of the LGBTQ+ community from stigma is a compelling state interest.

Background: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. Methods: We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. Results: Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. Conclusions: Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required. [ABSTRACT FROM AUTHOR]

It presents a study that describes a previously unidentified disorder we name LINKED (LINKage-specific deubiquitylation deficiency–induced Embryonic Defects) syndrome and reveals linkage-specific ubiquitin cleavage from chromatin remodelers as an essential signaling mode that coordinates chromatin remodeling during embryogenesis. It mentions about the reversible modification of proteins with linkage-specific ubiquitin chains.

The SARS-CoV-2 pandemic raises many scientific and clinical questions. These include how host genetic factors affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work has been conducted on other coronaviruses that affect different species. We reviewed the literature on host genetic factors related to coronaviruses, systematically focusing on human studies. We identified 1,832 articles of potential relevance. Seventy-five involved human host genetic factors, 36 of which involved analysis of specific genes or loci; aside from one meta-analysis, all were candidate-driven studies, typically investigating small numbers of research subjects and loci. Three additional case reports were described. Multiple significant loci were identified, including 16 related to susceptibility (seven of which identified protective alleles) and 16 related to outcomes (three of which identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Among other studies, 30 involved both human and non-human host genetic factors related to coronavirus, 178 involved study of non-human (animal) host genetic factors related to coronavirus, and 984 involved study of non-genetic host factors related to coronavirus, including involving immunopathogenesis. Previous human studies have been limited by issues that may be less impactful now, including low numbers of eligible participants and limited availability of advanced genomic methods; however, these may raise additional considerations. We outline key genes and loci from animal and human host genetic studies that may bear investigation in the study of COVID-19. We also discuss how previous studies may direct current lines of inquiry. [ABSTRACT FROM AUTHOR]

Germline pathogenic variants in chromatin-modifying enzymes are a common cause of pediatric developmental disorders. These enzymes catalyze reactions that regulate epigenetic inheritance via histone post-translational modifications and DNA methylation. Cytosine methylation (5-methylcytosine [5mC]) of DNA is the quintessential epigenetic mark, yet no human Mendelian disorder of DNA demethylation has yet been delineated. Here, we describe in detail a Mendelian disorder caused by the disruption of DNA demethylation. TET3 is a methylcytosine dioxygenase that initiates DNA demethylation during early zygote formation, embryogenesis, and neuronal differentiation and is intolerant to haploinsufficiency in mice and humans. We identify and characterize 11 cases of human TET3 deficiency in eight families with the common phenotypic features of intellectual disability and/or global developmental delay; hypotonia; autistic traits; movement disorders; growth abnormalities; and facial dysmorphism. Mono-allelic frameshift and nonsense variants in TET3 occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues; all but one such variant occur within the catalytic domain, and most display hypomorphic function in an assay of catalytic activity. TET3 deficiency and other Mendelian disorders of the epigenetic machinery show substantial phenotypic overlap, including features of intellectual disability and abnormal growth, underscoring shared disease mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: Work-related psychosocial risks are an increasingly important issue in occupational safety and health (OSH) policy. In Germany, as in many other European countries, employers are legally required to carry out workplace risk assessments (WRAs) and to account for psychosocial factors when doing this. The aim of this study was to expand the still scarce and sketchy empirical evidence on the extent to which employers comply with these obligations, as well as on possible determinants of compliance behaviour.Methods: Survey data from 6500 German companies were used to calculate the prevalence of workplace risk assessments that include psychosocial factors. Furthermore, multinomial logistic regressions were performed to explore which company characteristics influence the chance of psychosocial risk assessment occurrence.Results: The prevalence of psychosocial risk assessments was 21%. Next to company size (OR = 5.7, 95% CI 3.0-11.0), availability of safety specialist assistance (OR = 3.5, 95% CI 2.6-4.6), availability of occupational health specialist assistance (OR = 3.4; 95% CI 2.6-4.4) and inspection by OSH authority (OR = 3.4, 95% CI 2.4-4.7) were the strongest predictors of psychosocial risk assessment occurrence. Smaller (but still significant) effect sizes were found for the level of knowledge about legal OSH requirements, training of managers in OSH, economic situation of the company, presence of a works council, positive view on the benefit of OSH, affiliation with the production sector and magnitude of psychosocial risks within the company.Conclusions: The study results indicate large deficiencies in the implementation of psychosocial risk assessments, especially for small companies. Findings suggest that enhancing companies' utilisation of professional OSH experts and strengthening the advisory and control capacities of the OSH inspection authorities in the area of psychosocial risks would be beneficial for improving the current situation. [ABSTRACT FROM AUTHOR]

Family-scale rural digesters are widely implemented in Nepal for waste management, resource recovery, and environmental stewardship for distributed communities. However, there is little documentation on the microbial community structures in real-world family farm digesters. This work compared microbial community structures in four family digesters with a near-by municipal digester. Included in the family digesters was a high-altitude family digester located on Mt. Everest in Mosi, Nepal (2,634 m elevation). Differences in the community structures included the prevalence in family digesters of Bathyarchaeota MGC-6. MCG-6 is an archaeal population putatively involved in autotrophic acetate generation and conversion of cellulose to sugars. In addition, Rikenellaceae DMER64, a population thought to degrade sugars, was more prevalent in the family digesters. The ratio of Methanothrix to hydrogenotrophic methanogens was higher in the family digesters. In addition, the dominant species of syntrophic hydrogen-producing bacteria differed. Syntrophobacter and Syntrophomonas species, documented for their critical roles in waste activated sludge digesters, were not detected. In conclusion, observed differences in microbial community composition suggested a capacity to support different substrate conversion pathways and a major role of Archaea beyond methanogenesis among the studied digesters. [ABSTRACT FROM AUTHOR]

Comprehensive models of biomass pyrolysis are needed to develop renewable fuels and chemicals from biomass. Unfortunately, the detailed kinetic schemes required to optimize industrial biomass pyrolysis processes are too computationally expensive to include in models that account for both kinetics and transport within reacting particles. Here we present a machine learning approach using artificial neural networks and decision trees to reduce the computational expense of detailed kinetic models by four orders of magnitude, enabling their use in comprehensive models. The trained neural networks generalize very well, predicting the outputs of the detailed kinetic model with over 99.9% accuracy on new data. The machine learning approach we outline is not specific to kinetic modeling and can be applied to any set of input and output data, even if the underlying relationship between inputs and outputs is unknown. [ABSTRACT FROM AUTHOR]

Since the launch of IJAL 100 years ago, historical linguistics has been a central concern of researchers working on the languages of the Americas, and diachronic studies of New World language families have contributed substantially both to our knowledge of the development and dispersal of languages over time and to the refinement of the methods we use to study language history. This article surveys some of the most important developments over the past century, concentrating largely on work that has appeared in the Journal. [ABSTRACT FROM AUTHOR]

This study investigated the impacts of long-chain fatty acid (LCFA) feeding frequencies on microbial community structure, bioconversion kinetics, and process stability during anaerobic codigestion. Parallel laboratory-scale anaerobic codigesters fed with dairy cattle manure were either pulse-fed every two days or continuously-fed daily, respectively, with oleate (C 18:1 ) in incremental step increases over 200 days up to 64% of the influent chemical oxygen demand (COD). The effluent acetate concentration exceeded 3000 mg/L in the continuous-fed codigester at the highest oleate loading rate, but remained below 100 mg/L in the pulse-fed codigester at the end of its 48-hr oleate feed cycle. Maximum substrate conversion rates of oleate ( q max, oleate ) and acetate ( q max, acetate ) were significantly higher in the pulse-fed codigester compared to the continuous-fed codigester. 16S rRNA gene amplicon sequencing showed that Bacteria and Archaea community profiles diverged based on the codigester LCFA feeding pattern and loading rate. LCFA-degrading Syntrophomonas bacteria were significantly enriched in both LCFA codigesters relative to the control digester. The pulse-fed codigester had the highest community fraction of Syntrophomonas 16S rRNA genes by the end of the experiment with 43% of Bacteria amplicon sequences. q max, oleate and q max, acetate values were both significantly correlated to absolute concentrations of Syntrophomonas and Methanosaeta 16S rRNA genes, respectively. Multiple-linear regression models based on the absolute abundance of Syntrophomonas and Methanosaeta taxa provided improved predictions of oleate and acetate bioconversion kinetics, respectively. These results collectively suggest that pulse feeding rather than continuous feeding LCFA during anaerobic codigestion selected for higher microbial bioconversion kinetics and functional stability, which were related to changes in the physiological diversity and adaptive capacity of syntrophic and methanogenic communities. [ABSTRACT FROM AUTHOR]

Over the past 100 years, research on the indigenous languages of the Americas, much of it published in the pages of the International Journal of American Linguistics, has had a profound influence on every aspect of the field of linguistics. In this special centenary issue of IJAL, we begin with a brief survey of the impact Americanist studies have had on linguistics, with an emphasis on work published in our Journal, followed by five invited contributions examining in depth the past, present, and future of Americanist linguistics in specific sub-disciplines of linguistics. [ABSTRACT FROM AUTHOR]

draws a categorial distinction between language-particular terms - terms used in the description of specific languages - and comparative concepts - terms used for crosslinguistic comparison. This seems like a valid distinction for a lot of terminology, but it is also true that there are 'portable' terms that are suitable both for the description of specific languages and for crosslinguistic comparison. This descriptive metalanguage is analogous to the descriptive vocabulary employed in other observational sciences, and its elaboration is an important enterprise for both descriptivist and comparative linguists. [ABSTRACT FROM AUTHOR]

Background: Two variants of Methylobacterium extorquens AM1 demonstrated a trade-off between growth rate and biomass yield. In addition, growth rate and biomass yield were also affected by supplementation of growth medium with different amounts of cobalt. The metabolism changes relating to these growth phenomena as well as the trade-off were investigated in this study. 13C metabolic flux analysis was used to generate a detailed central carbon metabolic flux map with both absolute and normalized flux values. Results: The major differences between the two variants occurred at the formate node as well as within C3-C4 inter-conversion pathways. Higher relative fluxes through formyltetrahydrofolate ligase, phosphoenolpyruvate carboxylase, and malic enzyme led to higher biomass yield, while higher relative fluxes through pyruvate kinase and pyruvate dehydrogenase led to higher growth rate. These results were then tested by phenotypic studies on three mutants (null pyk, null pck mutant and null dme mutant) in both variants, which agreed with the model prediction. Conclusions: In this study, 13C metabolic flux analysis for two strain variants of M. extorquens AM1 successfully identified metabolic pathways contributing to the trade-off between cell growth and biomass yield. Phenotypic analysis of mutants deficient in corresponding genes supported the conclusion that C3-C4 inter-conversion strategies were the major response to the trade-off. [ABSTRACT FROM AUTHOR]

Although Workplace Risk Assessments (WRA) are legally required in all EU member states and widely considered to be a core element of occupational safety and health (OSH) management, the state of their implementation at company level is still viewed rather critically, both in quantitative and qualitative terms. In this study, data from a representative company survey ( N = 6500) were used to estimate the frequency of different patterns (and corresponding quality levels) of WRA practice in Germany and to determine organisational factors influencing the chance of occurence of these WRA patterns. Results show that only one out of four companies carry out WRAs which not only meet the essential procedural requirements but also take account of potential risk areas in a fairly comprehensive manner. Multinomial logistic regression analysis further revealed that company size is by far the strongest predictor of WRA activity, especially of its more developed forms. Availability of safety specialist assistance, availability of occupational health specialist assistance, affiliation to the production sector, presence of an employee representative body and a good economic situation of the company were each associated with WRA activity as well. The still considerable deficiencies in WRA coverage and quality indicated by this study clearly call for an intensification of WRA-related control and advisory efforts by the OSH authorities, primarily in small companies and in the private services sector. Findings also suggest that reinforcement of worker representation structures at company level and strengthening professional OSH expert utilisation would be beneficial for WRA implementation. [ABSTRACT FROM AUTHOR]

The article reviews Italian philosopher and theologian Thomas Aquinas' proofs for the existence of God and discusses Aquinas' Quinque Viae to prove God's existence. It concludes with an examination of proposals for sources of the Fourth Way, and argue that philosopher Plato is not an option and involves a careful exposition and examination of each part of the argument. It also mentions the value of this Fourth Way for current philosophical discussion.

The Principle of the Uniqueness of Grammatical Relations, which requires that all grammatical relations be distinguishable on morphological and/or syntactic grounds and non-repeatable in a clause, is often assumed to be a universal requirement of language and is a central tenet, explicit or implicit, of many theories of grammar. Upper Necaxa Totonac offers an apparent exception to this principle in that it has clauses with multiple objects that seem grammatically identical, yet do not appear to be adjuncts as they control agreement and are active in processes such as reciprocalization. Extensive testing of the properties of Upper Necaxa objects shows that, while a primary object can be distinguished on the basis of a single diagnostic, any remaining objects are indistinguishable and so must be treated as being governed by the same grammatical relation which is, therefore, non-unique. This data requires a reconsideration of the Uniqueness Principle as an absolute universal, and as an axiom or a necessary tenet of theories of human language. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain management is a major concern and a significant component of postoperative care pathways for surgery patients. Methods: We performed a retrospective medical record review of 233 consecutive patients undergoing major colorectal surgery from October 2011 to January 2013 at an academic medical center. All patients were managed with similar enhanced recovery pathways; 66 patients received multimodal postsurgical pain management that included liposomal bupivacaine intraoperatively, and 167 patients received conventional pain management with intravenous opioids. Comparisons were made using t test and chi-square analysis with StatView (SAS Institute Inc.). Results: Patients receiving multimodal pain management with liposomal bupivacaine injected in the surgical site at the end of major colorectal procedures had lower postoperative pain scores and used significantly less opioids at 12, 24, 36, 48, 60, and 72 hours (P=0.03). Patients in the multimodal group also had a significantly decreased risk of opioid-related adverse events, with decreased use of antipruritic medications and antiemetic medications postoperatively. A significant decrease in length of postoperative hospital stay was seen in the multimodal group (7.2 vs 9.0 days, P=0.04). Conclusion: The use of multimodal pain management including liposomal bupivacaine during major colorectal surgeries improved postoperative outcomes, decreased lengths of stay, and increased bed availability. [ABSTRACT FROM AUTHOR]

The article describes a case study on the impact of fluid status on access blood flow measurements as observed in a hospital-based hemodialysis unit servicing inpatients and outpatients. Topics mentioned include the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, percentage of clotted grafts that are associated with stenosis, and information on high-output cardiac failure.

We report observations on the dynamics of bacterial communities in response to methane stimulus in laboratory microcosm incubations prepared with lake sediment samples. We first measured taxonomic compositions of long-term enrichment cultures and determined that, although dominated by Methylococcaceae types, these cultures also contained accompanying types belonging to a limited number of bacterial taxa, methylotrophs and non-methylotrophs. We then followed the short-term community dynamics, in two oxygen tension regimens (150 μM and 15 μM), observing rapid loss of species diversity. In all microcosms, a single type of Methylobacter represented the major methane-oxidizing partner. The accompanying members of the communities revealed different trajectories in response to different oxygen tensions, with Methylotenera species being the early responders to methane stimulus under both conditions. The communities in both conditions were convergent in terms of their assemblage, suggesting selection for specific taxa. Our results support prior observations from metagenomics on distribution of carbon from methane among diverse bacterial populations and further suggest that communities are likely responsible for methane cycling, rather than a single type of microbe. [ABSTRACT FROM AUTHOR]

The ecophysiology of long-chain fatty acid-degrading syntrophic β-oxidizing bacteria has been poorly understood due to a lack of quantitative abundance data. Here, TaqMan quantitative PCR (qPCR) assays targeting the 16S rRNA gene of the known mesophilic syntrophic β-oxidizing bacterial genera Syntrophomonas and Syntrophus were developed and validated. Microbial community dynamics were followed using qPCR and Illumina-based high-throughput amplicon sequencing in triplicate methanogenic bioreactors subjected to five consecutive batch feedings of oleic acid. With repeated oleic acid feeding, the initial specific methane production rate significantly increased along with the relative abundances of Syntrophomonas and methanogenic archaea in the bioreactor communities. The novel qPCR assays showed that Syntrophomonas increased from 7 to 31% of the bacterial community 16S rRNA gene concentration, whereas that of Syntrophus decreased from 0.02 to less than 0.005%. High-throughput amplicon sequencing also revealed that Syntrophomonas became the dominant genus within the bioreactor microbiomes. These results suggest that increased specific mineralization rates of oleic acid were attributed to quantitative shifts within the microbial communities toward higher abundances of syntrophic β-oxidizing bacteria and methanogenic archaea. The novel qPCR assays targeting syntrophic β-oxidizing bacteria may thus serve as monitoring tools to indicate the fatty acid β-oxidization potential of anaerobic digester communities. [ABSTRACT FROM AUTHOR]

Background: Although the popularity of workplace health promotion (WHP) has considerably increased over the years, there are still concerns about the way this concept is being implemented by the companies. There is, however, a seeming lack of empirical knowledge about variations in WHP practice. Therefore, the aim of this study was to determine the prevalence of different patterns (and related quality levels) of WHP activity and the effect of organisational predictors on the chances of these WHP activity levels being implemented. Methods: Data from an establishment survey (N = 6,500) were used to calculate the prevalences of four configurations of WHP among German companies. Furthermore, multinominal logistic regressions were performed to determine odds ratios for these WHP activity levels according to several organisational characteristics. Results: 9% of companies exhibited the most comprehensive type of WHP including analysis, individual-directed prevention measures and participatory groups concerned with working conditions improvement (level A), 18% featured a combination of analysis and individual-directed prevention (level B), 29% had reported measures from only one of these categories (level C), and 44% showed no WHP activity at all (level D). In the multivariate analysis company size turned out to be the strongest predictor of WHP at all levels. WHP was also predicted by a good economic situation of the company, the availability of safety specialist assistance, the availability of specialist assistance in occupational health and the presence of an employee representative body. These effects usually became stronger when moving up in the hierarchy of WHP levels. For the two sector-level variables (private vs. public, production vs. services) no statistically significant associations with WHP were found. Conclusions: WHP still shows great potential for improvement both in quantitative and qualitative terms. Especially required are additional efforts in developing and implementing WHP practice models and dissemination strategies which are tailored to the particular conditions and needs of small companies. However, findings suggest that the chances for achieving progress in WHP also depend on developments in adjacent policy areas such as labour relations or occupational safety and health. [ABSTRACT FROM AUTHOR]

We sequenced the genomes of 19 methylotrophic isolates from Lake Washington, which belong to nine genera within eight families of the A lphaproteobacteria, two of the families being the newly proposed families. Comparative genomic analysis with a focus on methylotrophy metabolism classifies these strains into heterotrophic and obligately or facultatively autotrophic methylotrophs. The most persistent metabolic modules enabling methylotrophy within this group are the N-methylglutamate pathway, the two types of methanol dehydrogenase ( MxaFI and XoxF), the tetrahydromethanopterin pathway for formaldehyde oxidation, the serine cycle and the ethylmalonyl- CoA pathway. At the same time, a great potential for metabolic flexibility within this group is uncovered, with different combinations of these modules present. Phylogenetic analysis of key methylotrophy functions reveals that the serine cycle must have evolved independently in at least four lineages of A lphaproteobacteria and that all methylotrophy modules seem to be prone to lateral transfers as well as deletions. [ABSTRACT FROM AUTHOR]

Background: Postoperative ileus is a significant clinical challenge lacking effective management strategies. Ghrelin-receptor stimulation has promotility effects in the upper and lower gastrointestinal tract. Objective: This proof-of-concept, phase 2, randomized study evaluated the safety and efficacy of the ghrelin-receptor agonist ipamorelin in the treatment of postoperative ileus following abdominal surgery (ClinicalTrials.gov NCT00672074). Design: The design was a multicenter, double-blind, placebo-controlled, clinical trial. Settings: The settings include hospital inpatients. Patients: The patients were adults undergoing small and large bowel resection by open or laparoscopic surgery. Intervention: The intervention was intravenous infusions of 0.03-mg/kg ipamorelin vs placebo twice daily, on postoperative day 1 to 7 or hospital discharge. Main outcome measures: Safety was assessed by monitoring adverse events and laboratory tests. The key efficacy endpoint was time from first dose of study drug to tolerance of a standardized solid meal. Results: One hundred seventeen patients were enrolled, of whom 114 patients composed the safety and modified intent-to-treat populations. Demographic and disease characteristics were balanced between groups. Overall incidence of any treatment-emergent adverse events was 87.5 % in the ipamorelin group and 94.8 % in placebo group. Median time to first tolerated meal was 25.3 and 32.6 h in the ipamorelin and placebo groups, respectively ( p = 0.15). Limitations: This proof of concept study was small and enrolled patients with a broad range of underlying conditions. Conclusions: Ipamorelin 0.03-mg/kg twice daily for up to 7 days was well tolerated. There were no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses. [ABSTRACT FROM AUTHOR]

We describe five novel Methylophilaceae ecotypes from a single ecological niche in Lake Washington, USA, and compare them to three previously described ecotypes, in terms of their phenotype and genome sequence divergence. Two of the ecotypes appear to represent novel genera within the Methylophilaceae. Genome-based metabolic reconstruction highlights metabolic versatility of Methylophilaceae with respect to methylotrophy and nitrogen metabolism, different ecotypes possessing different combinations of primary substrate oxidation systems (MxaFI-type methanol dehydrogenase versus XoxF-type methanol dehydrogenase; methylamine dehydrogenase versus N-methylglutamate pathway) and different potentials for denitrification (assimilatory versus respiratory nitrate reduction). By comparing pairs of closely related genomes, we uncover that site-specific recombination is the main means of genomic evolution and strain divergence, including lateral transfers of genes from both closely- and distantly related taxa. The new ecotypes and the new genomes contribute significantly to our understanding of the extent of genomic and metabolic diversity among organisms of the same family inhabiting the same ecological niche. These organisms also provide novel experimental models for studying the complexity and the function of the microbial communities active in methylotrophy. [ABSTRACT FROM AUTHOR]

Federal urban relocation programs for American Indians, commonly believed to have been launched in the 1950s, were actually first initiated under the aegis of John Collier's Office of Indian Affairs. As the case study of OIA Placement Officer Scott Henry Peters shows, federal officials recognized by the early 1930s that significant numbers of American Indians were migrating off-reservation. As an American Indian working for the Indian Office, Peters attempted to provide employment opportunities for young American Indian adults migrating to cities and help them adapt to modern urban life. This article extends the literature on urban American Indian history back in time and reveals some of the contradictions inherent in Collier's policy initiatives. [ABSTRACT FROM AUTHOR]

Despite advances in pharmacologic options for the management of surgical pain, there appears to have been little or no overall improvement over the last two decades in the level of pain experienced by patients. The importance of adequate and effective surgical pain management, however, is clear, because inadequate pain control 1) has a wide range of undesirable physiologic and immunologic effects; 2) is associated with poor surgical outcomes; 3) has increased probability of readmission; and 4) adversely affects the overall cost of care as well as patient satisfaction. There is a clear unmet need for a national surgical pain management consensus task force to raise awareness and develop best practice guidelines for improving surgical pain management, patient safety, patient satisfaction, rapid postsurgical recovery, and health economic outcomes. To comprehensively address this need, the multidisciplinary Surgical Pain Congress™ has been established. The inaugural meeting of this Congress (March 8 to 10, 2013, Celebration, Florida) evaluated the current surgical pain management paradigm and identified key components of best practices. [ABSTRACT FROM AUTHOR]

The article discusses the writing of county natural history in England from the 1640s through the 1680s. An overview of the English antiquarian John Aubrey, including the role that the mid 17th century English Civil War played in his desire to research England's antiquities, is provided. The English county historian Robert Plot's role in the research of local English history is discussed.

The article informs that the genetic variants that suppress antiviral immunity are linked to severe COVID-19. Topics include the adaptive immune system, including both B and T cells, has been recognized to play a critical role in providing preexisting immunity to SARS-CoV-2; small-scale studies have implicated the type I interferon (IFN) pathway as protective against SARS-CoV-2; and the type I IFN pathway plays a crucial role in mediating innate immune responses to viral infections.

A thermostabilized variant (UVF) of the engrailed homeodomain (EnHD) was previously engineered by Mayo and co-workers. The melting temperature of the non-natural, designed protein is 50°C higher than the natural wild-type protein (>99 vs. 52°C), and the two proteins share 22% sequence identity. We have performed extensive (1 μs) all-atom, explicit solvent molecular dynamics simulations of the wild-type and engineered proteins to investigate their structural and dynamic properties at room temperature and at 100°C. Our simulations are in good agreement with nuclear magnetic resonance data available for the two proteins [nuclear Overhauser effect crosspeaks (NOEs), J-coupling constants and order parameters for EnHD; and NOEs for UVF], showing that we reproduce the backbone dynamics and side chain packing in the native state of both proteins. UVF was more dynamic at room temperature than EnHD, with respect to both its backbone and side chain motion. When the temperature was raised, the thermostable protein maintained this mobility while retaining its native conformation. EnHD, on the other hand, was unable to maintain its more rigid native structure at higher temperature and began to unfold. Heightened protein dynamics leading to promiscuous and dynamically interchangeable amino acid contacts makes UVF more tolerant to increasing temperature, providing a molecular explanation for heightened thermostability of this protein. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations of protein folding or unfolding, unlike most in vitro experimental methods, are performed on a single molecule. The effects of neighboring molecules on the unfolding/ folding pathway are largely ignored experimentally and simply not modeled computationally. Here, we present two all-atom, explicit solvent molecular dynamics simulations of 32 copies of the Engrailed homeodomain (EnHD), an ultrafast-folding and -unfolding protein for which the folding/unfolding pathway is well-characterized. These multimolecule simulations, in comparison with single-mole-cule simulations and experimental data, show that intermolecular interactions have little effect on the folding/unfolding pathway. EnHD unfolded by the same mechanism whether it was simulated in only water or also in the presence of other EnHD molecules. It populated the same native state, transition state, and folding intermediate in both simulation systems, and was in good agree-ment with experimental data available for each of the three states. Unfolding was slowed slightly by interactions with neighboring proteins, which were mostly hydrophobic in nature and ultimately caused the proteins to aggregate. Protein-water hydrogen bonds were also replaced with protein-protein hydrogen bonds, addition-ally contributing to aggregation. Despite the increase in protein-pro-tein interactions, the protein aggregates formed in simulation did not do so at the total exclusion of water. These simulations support the use of single-molecule techniques to study protein unfolding and also provide insight into the types of interactions that occur as pro-teins aggregate at high temperature at an atomic level. [ABSTRACT FROM AUTHOR]

This article explores the educational journey of one man from leaving school in the mid-1970s, at the age of 14, through a period of chaotic drug use, and on to developing his career helping other chaotic drug users back into a “normal” life. Although focused on someone with drug dependency as part of his history, the article exposes issues that potentially underlie the experiences of many learners within working-class communities. In particular, it examines the role of formal and informal education, considers education's ability to liberate or domesticate (Freire, 1972), and examines approaches to learning that support recovery and transformation. [ABSTRACT FROM PUBLISHER]

Methylotenera species, unlike their close relatives in the genera Methylophilus, Methylobacillus, and Methylovorus, neither exhibit the activity of methanol dehydrogenase nor possess mxaFI genes encoding this enzyme, yet they are able to grow on methanol. In this work, we integrated a genome-wide proteomics approach, shotgun proteomics, and a genome-wide transcriptomics approach, shotgun transcriptome sequencing (RNA-seq), of Methylotenera mobilis JLW8 to identify genes and enzymes potentially involved in methanol oxidation, with special attention to alternative nitrogen sources, to address the question of whether nitrate could play a role as an electron acceptor in place of oxygen. Both proteomics and transcriptomics identified a limited number of genes and enzymes specifically responding to methanol. This set includes genes involved in oxidative stress response systems, a number of oxidoreductases, including XoxF-type alcohol dehydrogenases, a type II secretion system, and proteins without a predicted function. Nitrate stimulated expression of some genes in assimilatory nitrate reduction and denitrification pathways, while ammonium downregulated some of the nitrogen metabolism genes. However, none of these genes appeared to respond to methanol, which suggests that oxygen may be the main electron sink during growth on methanol. This study identifies initial targets for future focused physiological studies, including mutant analysis, which will provide further details into this novel process. [ABSTRACT FROM AUTHOR]

This paper uses the comparative method of historical linguistics to investigate the hypothesis that languages of two well-established families of Mesoamerica, Totonacan and Mixe-Zoquean, are related in a larger genetic grouping dubbed Totozoquean. Proposed cognate sets comparing words reconstructed for Proto-Totonacan (PTn) and Proto-Mixe-Zoquean (PMZ) show regular sound correspondences attesting to the descent of these two languages from Proto-Totozoquean (PTz). Identification of sound correspondences facilitates reconstruction of PTz's phonological inventory and vocabulary. The PMZ words used in the comparison are from Wichmann (1995). The PTn words are reconstructed by the authors, who provide the Totonacan cognate sets on which these reconstructions are based, as well as discussion of the classification and phonological history of Totonacan languages. Evidence is cited indicating that Totozoquean is comparable to Indo-European in chronological depth. [ABSTRACT FROM AUTHOR]

The existence of restricted or phraseologized complex expressions such as clichéés, collocations, and idioms (collectively known as phrasemes) is well-known and widely accepted in the domain of multi-word expressions. What is not so widely recognized is the existence of the same type of phraseologized expression at the morphological level -- restricted complex morphological expressions, or morphological phrasemes. Morphological phrasemes, found in both derivation and inflection, are governed by the same principles of phraseologization that govern phrasemes at the lexical-syntactic level, and have roughly the same subtypes, including morphological collocations and morphological idioms. In addition to offering clear advantages in terms of useful descriptive practice and formal economy, the recognition of phraseologized morphological expressions makes clear the parallels between linguistic signs at the lexical and morphemic level, this isomorphism falling out from the conventionalized nature of the mapping between linguistic meaning and linguistic form. Contrary to many current approaches to morphological theory that reject the morpheme as a meaning-bearing element in the structure of words, this paper argues that the existence of conventionalized uses of sublexical elements gives strong support to the utility of the morpheme as unit of linguistic analysis. [ABSTRACT FROM AUTHOR]

In recent years, techniques have been developed and perfected for high-throughput identification of proteins and their accurate partial sequencing by shotgun nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS), making it feasible to assess global protein expression profiles in organisms with sequenced genomes. We implemented comprehensive proteomics to assess the expressed portion of the genome of Methylobacillus flagellatus during methylotrophic growth. We detected a total of 1,671 proteins (64% of the inferred proteome), including all the predicted essential proteins. Nonrandom patterns observed with the nondetectable proteins appeared to correspond to silent genomic islands, as inferred through functional profiling and genome localization. The protein contents in methylamine- and methanol-grown cells showed a significant overlap, confirming the commonality of methylotrophic metabolism downstream of the primary oxidation reactions. The new insights into methylotrophy include detection of proteins for the N-methylglutamate methylamine oxidation pathway that appears to be auxiliary and detection of two alternative enzymes for both the 6-phosphogluconate dehydrogenase reaction (GndA and GndB) and the formate dehydrogenase reaction (FDH1 and FDH4). Mutant analysis revealed that GndA and FDH4 are crucial for the organism's fitness, while GndB and FDH1 are auxiliary. [ABSTRACT FROM AUTHOR]

This article explores the practice of collecting artifacts and studying the material culture of the Menominee of Wisconsin during the late 19th and early 20th centuries. The belief among non-Indians that Native American culture was dying and needed to be preserved through museum collections, the role of scholars in introducing Menominee culture to non-Indian populations, and the consequences of their collection practices are explored. Particular focus is given to the work of scholars and museum collectors including Walter J. Hoffman, Alanson Buck Skinner, and Samuel Barrett.

Methylotrophs, organisms able to gain energy and carbon from compounds containing no carbon–carbon bonds, such as methane, methanol and methylated amines, are widespread in nature. However, knowledge of their nutrient preference and their metabolism is mostly based on experiments with cultures grown in defined laboratory conditions. Here, we use transcriptomics to explore the activity of one methylotroph, Methyotenera mobilis in its natural environment, lake sediment from which it has been previously isolated. Cells encapsulated in incubation cassettes were exposed to sediment conditions, with or without supplementation with a carbon/energy source (methylamine), and gene-expression patterns were compared for those cells to patterns for cells incubated in a defined medium supplemented with methylamine. A few specific trends in gene expression were observed at in situ conditions that may be of environmental significance, as follows. Expression of genes for the linear formaldehyde oxidation pathway linked to tetrahydromethanopterin increased, suggesting an important role for this pathway in situ, in contrast to laboratory condition culture, in which the cyclic ribulose monophosphate pathway seemed to be the major route for formaldehyde oxidation. Along with the ribulose monophosphate cycle that is also a major pathway for assimilating C1 units, the methylcitric acid cycle seemd to be important in situ, suggesting that multicarbon compounds may be the natural carbon and/or energy substrates for M. mobilis, challenging the notion of an obligately methylotrophic lifestyle for this bacterium. We also detected a major switch in expression of genes responsible for the mode of motility between different conditions: from flagellum-enabled motility in defined medium to in situ expression of pili known to be involved in twitching motility and adherence. Overall, this study offers a novel approach for gaining insights into the lifestyle of individual microbes in their native environments. [ABSTRACT FROM AUTHOR]

A great deal has been written about causatives and applicatives, yet efforts to relate these two types of valency-increaser are still in their early stages. This paper is an attempt to develop a unified treatment using data from the Salishan language Lushootseed, which derives its transitive verb stems from intransitive radicals using a variety of valency- increasing suffixes. This paper proposes a taxonomy of these suffixes based on two parameters--the distinction between a causative, which adds a subject, and an applicative, which adds an object, and the distinction between direct and nondirect--that is, whether the causee or the applied object is a direct object or is more oblique. This study also touches on some current debates in Salishan studies about whether these morphemes are infectional or derivational, and the extent to which verbal radicals can be treated as uniformly unaccusative, a characterization of the family that has been used to motivate some significant claims about language universals. [ABSTRACT FROM AUTHOR]

Here, we compare the distributions of main chain (ΦΨ) angles (i.e., Ramachandran maps) of the 20 naturally occurring amino acids in three contexts: (i) molecular dynamics (MD) simulations of Gly-Gly-X-Gly-Gly pentapeptides in water at 298 K with exhaustive sampling, where X = the amino acid in question; (ii) 188 independent protein simulations in water at 298 K from our Dynameomics Project; and (iii) static crystal and NMR structures from the Protein Data Bank. The GGXGG peptide series is often used as a model of the unstructured denatured state of proteins. The sampling in the peptide MD simulations is neither random nor uniform. Instead, individual amino acids show preferences for particular conformations, but the peptide is dynamic, and interconversion between conformers is facile. For a given amino acid, the (ΦΨ) distributions in the protein simulations and the Protein Data Bank are very similar and often distinct from those in the peptide simulations. Comparison between the peptide and protein simulations shows that packing constraints, solvation. and the tendency for particular amino acids to be used for specific structural motifs can overwhelm the "intrinsic propensities" of amino acids for particular (4,'I') conformations. We also compare our helical propensities with experimental consensus values using the host-guest method, which appear to be determined largely by context and not necessarily the intrinsic conformational propensities of the guest residues. These simulations represent an improved coil library free from contextual effects to better model intrinsic conformational propensities and provide a detailed view of conformations making up the "random coil" state. [ABSTRACT FROM AUTHOR]

The principle of microscopic reversibility states that at equilibrium the number of molecules entering a state by a given path must equal those exiting the state via the same path under identical conditions or, in structural terms, that the conformations along the two pathways are the same. There has been some indirect evidence indicating that protein folding is such a process, but there have been few conclusive findings. In this study, we performed molecular dynamics simulations of an ultrafast unfolding and folding protein at its melting temperature to observe, on an atom-by-atom basis, the pathways the protein followed as it unfolded and folded within a continuous trajectory. In a total of 0.67 µs of simulation in water, we found six transient denaturing events near the melting temperature (323 and 330 K) and an additional refolding event following a previously identified unfolding event at a high temperature (373 K). In each case, unfolding and refolding transition state ensembles were identified, and they agreed well with experiment on the basis of a comparison of S and Φ values. On the basis of several structural properties, these 13 transition state ensembles agreed very well with each other and with four previously identified transition states from high-temperature denaturing simulations. Thus, not only were the unfolding and refolding transition states part of the same ensemble, but in five of the seven cases, the pathway the protein took as it unfolded was nearly identical to the subsequent refolding pathway. These events provide compelling evidence that protein folding is a microscopically reversible process. In the other two cases, the folding and unfolding transition states were remarkably similar to each other but the paths deviated. [ABSTRACT FROM AUTHOR]