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This study investigated the presence of Aeromonas spp. on a dairy farm in central Texas that employed a free-stall management system. A total of 140 samples were collected from areas of two different barns. Twenty-two presumptive Aeromonas isolates were cultured. Phenotypic analysis identified five Aeromonas spp. Twenty isolates exhibited β-lactam and one displayed tetracycline resistance. Phylogenetic analysis of the WGS data suggested only four Aeromonas spp. All isolates possessed at least one β-lactam resistance gene and one isolate possessed tet(E). No plasmids were identified from sequence alignments. Virulence genes were identified in all four Aeromonas spp. Mobility elements were identified in three of these, with the exception being A. dhakensis. Four of the transposons identified in this study have been associated with multidrug resistance in Italy, Sweden, and Singapore. There was no significant difference in the proportion of isolates from either barn. The absence of plasmids suggests mobility elements and virulence genes were localized to the chromosome. On a dairy farm of healthy cattle, these 22 Aeromonas isolates were considered normal environmental flora while illustrating the ubiquitous nature of Aeromonas spp. globally.

The bromodomain and extra terminal (BET) family of proteins are an integral part of human epigenome regulation, the dysregulation of which is implicated in multiple oncology and inflammatory diseases. Disrupting the BET family bromodomain acetyl-lysine (KAc) histone protein-protein interaction with small-molecule KAc mimetics has proven to be a disease-relevant mechanism of action, and multiple molecules are currently undergoing oncology clinical trials. This work describes an efficiency analysis of published GSK pan-BET bromodomain inhibitors, which drove a strategic choice to focus on the identification of a ligand-efficient KAc mimetic with the hypothesis that lipophilic efficiency could be drastically improved during optimization. This focus drove the discovery of the highly ligand-efficient and structurally distinct benzoazepinone KAc mimetic. Following crystallography to identify suitable growth vectors, the benzoazepinone core was optimized through an explore-exploit structure-activity relationship (SAR) approach while carefully monitoring lipophilic efficiency to deliver I-BET432 (

Niche environmental conditions influence both the structure and function of microbial communities and the cellular function of individual strains. The terrestrial subsurface is a dynamic and diverse environment that exhibits specific biogeochemical conditions associated with depth, resulting in distinct environmental niches. Here, we present the characterization of seven distinct strains belonging to the genus Arthrobacter isolated from varying depths of a single sediment core and associated groundwater from an adjacent well. We characterized genotype and phenotype of each isolate to connect specific cellular functions and metabolisms to ecotype. Arthrobacter isolates from each ecotype demonstrated functional and genomic capacities specific to their biogeochemical conditions of origin, including laboratory-demonstrated characterization of salinity tolerance and optimal pH, and genes for utilization of carbohydrates and other carbon substrates. Analysis of the Arthrobacter pangenome revealed that it is notably open with a volatile accessory genome compared to previous pangenome studies on other genera, suggesting a high potential for adaptability to environmental niches.

Bacillus cereus strain CPT56D-587-MTF (CPTF) was isolated from the highly contaminated Oak Ridge Reservation (ORR) subsurface. This site is contaminated with high levels of nitric acid and multiple heavy metals. Amplicon sequencing of the 16S rRNA genes (V4 region) in sediment from this area revealed an amplicon sequence variant (ASV) with 100% identity to the CPTF 16S rRNA sequence. Notably, this CPTF-matching ASV had the highest relative abundance in this community survey, with a median relative abundance of 3.77% and comprised 20%-40% of reads in some samples. Pangenomic analysis revealed that strain CPTF has expanded genomic content compared to other B. cereus species-largely due to plasmid acquisition and expansion of transposable elements. This suggests that these features are important for rapid adaptation to native environmental stressors. We connected genotype to phenotype in the context of the unique geochemistry of the site. These analyses revealed that certain genes (e.g. nitrate reductase, heavy metal efflux pumps) that allow this strain to successfully occupy the geochemically heterogenous microniches of its native site are characteristic of the B. cereus species while others such as acid tolerance are mobile genetic element associated and are generally unique to strain CPTF.

Invited Clinical Commentary BACKGROUND: Arthritis is one of the most frequently reported causes of disability in the United States and the prevalence is expected to increase in the coming decades. While many rheumatic diseases involve hand impairments, most are systemic and involve more than the musculoskeletal system. Functional and work disability are high and people would benefit from the services of occupational and physical therapists.This paper reviews concepts of self-management, and symptoms that contribute to limitations and restrictions to participation in daily life in people with rheumatic diseases and suggests roles for hand therapists beyond the immediate hand impairments.The impact of selected rheumatic diseases on functional and work disability are reviewed along with strategies for symptom management and self-management. Upper extremity impairments of selected rheumatic diseases are also discussed.The role for hand therapists in evaluating and addressing the complex needs of persons with rheumatic diseases, including less common diseases, is discussed. Outcome measures for fatigue, muscle involvement, ergonomics and computer use, and work disability are introduced. Finally, strategies for self-management and prevention of work and functional disability, along with symptom management for fatigue and pain are presented.Hand therapists can play a vital role in chronic rheumatic disease management to improve self-management and increase participation in meaningful activities. Patients, primary care and rheumatology providers need to be educated about the scope of services occupational and physical therapists provide beyond the hand impairments.

Many indigenous non-Caucasian populations, including Native Americans, have been reported to have higher rates, distinct clinical phenotypes, increased complications, and greater severity of systemic sclerosis (SSc). However, little is known of SSc specifically in Native Americans of the American Southwest. This study compared the clinical and serologic manifestations and outcomes of SSc in Native Americans and non-Native Americans (non-Natives) of this region.This cross-sectional retrospective study included 137 SSc patients (109 [80%] were non-Native and 28 [20%] were Native Americans) followed over a mean of 11.5 ± 7.6 years. Participants were repetitively evaluated with medical history, physical examination, echocardiography, chest imaging, and serologic testing. Disease characteristics and outcomes were statistically compared between Native Americans and non-Native patients.The estimated prevalence of SSc in Native Americans was 40.0 cases/100 000 vs 17.1 cases/100 000 for non-Natives (odds ratio 2.34, 95% confidence interval [CI] 1.55-3.55, P .001). The cohorts were similar in terms age, age of onset, limited vs diffuse cutaneous SSc, telangiectasias, gastroesophageal reflux disease, Raynaud phenomenon, serologies, interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, cancer prevalence, and overall mortality (all P .05). However, for Native Americans, mortality specifically from fatal infections was 3.94-fold that of non-Natives (hazard ratio 6.88, 95% CI 1.37-34.64; P .001).In Native Americans of the American Southwest, SSc is increased in prevalence but is phenotypically similar to SSc in non-Natives. However, mortality due specifically to infection is increased in Native Americans with SSc.

Although the mean age of onset of social anxiety disorder (SAD) is during adolescence, we know relatively little about the neurodevelopmental correlates of subsyndromal social anxiety in early adolescence before SAD manifests. Here we examined frontal EEG alpha/delta ratio (a putative proxy of brain maturation) in relation social anxiety symptoms across early adolescence. Resting regional EEG spectral power measures were collected continuously for 4 min (2 min eyes-open, 2 min eyes-closed) in slow (i.e., delta) and fast (i.e., alpha) frequencies at Time 1, and self-reported social anxiety measures were collected concurrently at Time 1 and then prospectively approximately one year later (Time 2) in 103 typically developing 12- to 14-year-olds (46.6% female, M

Objective: Certain Hispanic/Latino (Hispanic) populations have been reported to have higher rates and severity of systemic sclerosis; however, little is known of systemic sclerosis in the American Southwest. This study compared manifestations of systemic sclerosis in Hispanics with non-Hispanics of New Mexico. Methods: This cross-sectional longitudinal study included 109 systemic sclerosis patients followed over a mean of 12.6 ± 8.9 years. Subjects were repetitively evaluated including physical examination, echocardiography, chest imaging, and serologic testing and observed for complications. Disease characteristics and long-term outcomes were statistically compared between self-identified Hispanic and non-Hispanic subjects. Results: A total of 73 (67%) systemic sclerosis subjects were Hispanic and 36 (33%) were non-Hispanic. The cohorts were similar in mean age, age of systemic sclerosis onset, limited versus diffuse cutaneous systemic sclerosis, telangiectases, gastroesophageal reflux disease, Raynaud’s phenomenon, autoantibody profile, interstitial lung disease, pulmonary hypertension, scleroderma renal crisis, mortality, and comorbid malignancy (all p > 0.05). However, the standardized mortality ratio was increased in both cohorts relative to age-adjusted mortality: Hispanic: 2.08, confidence interval (1.94–2.24); non-Hispanic: 1.56, confidence interval (1.46–1.68). Furthermore, the standardized incidence ratio for malignancy was increased in both cohorts: Hispanic: 1.45, confidence interval (1.35–1.56); non-Hispanic: 1.24, confidence interval (1.16–1.34). The mean age of cancer diagnosis occurred at a significantly younger age in Hispanics (Hispanics: 53.1 ± 9.7 years; non-Hispanics 63.7 ± 7.9 years; 95% confidence interval: −19 ⩽ 10.6 ⩽ 2.2; p = 0.016). Conclusion: Systemic sclerosis phenotype, autoantibodies, complications, outcomes, malignancy rates, and mortality are generally similar between Hispanics and non-Hispanics with systemic sclerosis in the American Southwest. However, age-adjusted comorbid malignancy and mortality rates are significantly increased in both groups.

The sodium iodide symporter (NIS) is required for iodide uptake, which facilitates thyroid hormone biosynthesis. NIS has been exploited for over 75 years in ablative radioiodine (RAI) treatment of thyroid cancer, where its ability to transport radioisotopes depends on its localization to the plasma membrane. The advent of NIS-based in vivo imaging and theranostic strategies in other malignancies and disease modalities has recently increased the clinical importance of NIS. However, NIS trafficking remains ill-defined. Here, we used tandem mass spectrometry followed by coimmunoprecipitation and proximity ligation assays to identify and validate two key nodes—ADP-ribosylation factor 4 (ARF4) and valosin-containing protein (VCP)—controlling NIS trafficking. Using cell-surface biotinylation assays and highly inclined and laminated optical sheet microscopy, we demonstrated that ARF4 enhanced NIS vesicular trafficking from the Golgi to the plasma membrane, whereas VCP—a principal component of endoplasmic reticulum (ER)–associated degradation—governed NIS proteolysis. Gene expression analysis indicated VCP expression was particularly induced in aggressive thyroid cancers and in patients who had poorer outcomes following RAI treatment. Two repurposed FDA-approved VCP inhibitors abrogated VCP-mediated repression of NIS function, resulting in significantly increased NIS at the cell-surface and markedly increased RAI uptake in mouse and human thyroid models. Collectively, these discoveries delineate NIS trafficking and highlight the new possibility of systemically enhancing RAI therapy in patients using FDA-approved drugs.Significance:These findings show that ARF4 and VCP are involved in NIS trafficking to the plasma membrane and highlight the possible therapeutic role of VCP inhibitors in enhancing radioiodine effectiveness in radioiodine-refractory thyroid cancer.

Significant co-localization and trafficking of ARF4-dsRED and NIS-GFP proteins in co-incident vesicles at the plasma membrane in HeLa cells

Fletcher A et al Supplementary Information

The sodium iodide symporter NIS is endosomally trafficked in association with clathrin

Lack of co-trafficking for VCP-dsRED and NIS-GFP suggests that the site of functional interaction between VCP and NIS is distant to the plasma membrane in HeLa cells

Fletcher A et al Data Source File

Multiple heavy metal contamination is an increasingly common global problem. Heavy metals have the potential to disrupt microbially mediated biogeochemical cycling. However, systems-level studies on the effects of combinations of heavy metals on bacteria are lacking. For this study, we focused on the Oak Ridge Reservation (ORR; Oak Ridge, TN, USA) subsurface which is contaminated with several heavy metals and high concentrations of nitrate. Using a native Bacillus cereus isolate that represents a dominant species at this site, we assessed the combined impact of eight metal contaminants, all at site-relevant concentrations, on cell processes through an integrated multi-omics approach that included discovery proteomics, targeted metabolomics, and targeted gene-expression profiling. The combination of eight metals impacted cell physiology in a manner that could not have been predicted from summing phenotypic responses to the individual metals. Exposure to the metal mixture elicited a global iron starvation response not observed during individual metal exposures. This disruption of iron homeostasis resulted in decreased activity of the iron-cofactor-containing nitrate and nitrite reductases, both of which are important in biological nitrate removal at the site. We propose that the combinatorial effects of simultaneous exposure to multiple heavy metals is an underappreciated yet significant form of cell stress in the environment with the potential to disrupt global nutrient cycles and to impede bioremediation efforts at mixed waste sites. Our work underscores the need to shift from single- to multi-metal studies for assessing and predicting the impacts of complex contaminants on microbial systems.

Optical trapping and Mie Spectroscopy are used to measure the refractive index of organic matter extracted from the atmosphere in the UV wavelength range.

The 3-substituted chromane core is found in several bioactive natural products. Herein, we describe a route to 3-fluorinated chromanes from allylic phenol ethers. Our external oxidant-free approach takes advantage of an electro-chemical generation of a hypervalent iodine species, difluoro-λ3-tolyl iodane, which mediates the alkene fluoroaryla-tion. High yields and selectivity for this transformation are achieved for electron poor substrates. The redox chemistry has been characterized for the electrochemical generation of the iodane in the presence of fluoride, and insights into the mechanism are given. The transformation has been demonstrated on larger gram scales, which represents the potential broader utility of the process.

Objective: The aim of this study is to examine validity, reliability, and responsiveness to change of Patient-Reported Outcomes Measurement Information System Self-Efficacy for Managing Chronic Conditions in persons with systemic sclerosis. Methods: We conducted a post hoc analysis of the Patient-Reported Outcomes Measurement Information System Self-Efficacy measure and other quality-of-life measures from systemic sclerosis participants from a 16-week randomized control trial. The trial compared an Internet-based self-management program to a control condition where participants were provided an educational book. All participants completed outcome measures at baseline and following the 16-week trial period. Results: The mean age of participants was 53.7 years, 91% were female and systemic sclerosis subtype included 44.9% limited/sine and 43.1% diffuse; mean disease duration was 9.0 years. All self-efficacy subscales (Managing Emotions, Symptoms, Daily Activities, Social Interactions, and Medications/Treatment) demonstrated good internal consistency (.92–.96). All subscales showed statistically significant correlations with other validated measures of depressive symptoms and quality of life (.20–.86) but were not associated with satisfaction nor with appearance. The subscales appropriately discriminated between those with and without depressive symptoms and demonstrated responsiveness to change over the 16-week period for those who had a corresponding increase in reported quality of life. Conclusion: The Patient-Reported Outcomes Measurement Information System Self-Efficacy measure is valid, reliable, and responsive to change for persons with systemic sclerosis.

BACKGROUND Hand disease severity in people with systemic sclerosis (SSc) arises from connective tissue and vascular changes causing functional limitations, pain, and disability. Fatigue is not well-understood in SSc and reported to be highly distressing. It is not known how fatigue relates to these disease changes. The objective of this study was to identify which elements of hand disease severity contribute to fatigue in individuals with SSc. METHODS Five online databases and Google Scholar were searched to identify publications through 2021 presenting data related to hand disease severity and fatigue. RESULTS Five articles met the inclusion criteria. The samples were 72-91% female, and 35-100% with diffuse SSc. Measures of disease severity included skin thickening (modified Rodnan score), joint involvement (mobility, tenderness, swelling), and digital ulcers. Fatigue was measured by various self-report. Joint involvement was strongly associated with fatigue. Skin thickening weakly associated with fatigue. The perceived interference of digital ulcers in daily activities was related to fatigue. CONCLUSIONS Few studies have examined how fatigue relates to hand disease severity. While joint involvement was associated with fatigue over time and in cross-sectional studies, digital ulcers may be associated with fatigue indirectly. A conceptual model is proposed with implications for future research.Implications for RehabilitationStructural disease changes that manifest in the hands, is often associated with pain, disability, and fatigue in SSc.Fatigue is one of the most distressing symptoms of SSc and reported by 61-90% of individuals with SSc, but is not well characterized.Of measures of hand disease severity, joint involvement (contractures, swollen and tender joints) is most associated with fatigue in individuals with SSc and more so if pain is involved.A better understanding of the physiological features of disease and fatigue could provide insight into development of fatigue management interventions and help rheumatology providers work with patients to manage their fatigue.Rehabilitation assessments and interventions for hand disability need to be considered as important elements in improving all elements of quality of life for individuals with systemic sclerosis.

Transformer2 proteins (Tra2α and Tra2β) control splicing patterns in human cells, and no human phenotypes have been associated with germline variants in these genes. The aim of this work was to associate germline variants in the TRA2B gene to a novel neurodevelopmental disorder.Twelve individuals from 11 unrelated families who had predicted loss-of-function monoallelic variants, mostly de novo, were recruited. RNA-seq and Western blot analyses of Tra2β-1 and Tra2β-3 isoforms from patient-derived cells were performed. Tra2β1-GFP, Tra2β3-GFP and CHEK1 exon 3 plasmids were transfected into HEK-293 cells.All variants clustered in the 5' part of TRA2B, upstream of an alternative translation start site responsible for the expression of non-canonical Tra2β-3 isoform. All of affected individuals presented intellectual disability and/or developmental delay, frequently associated with infantile spasms, microcephaly, brain anomalies, autism spectrum disorder, feeding difficulties, and short stature. Experimental studies showed that these variants decreased the expression of the canonical Tra2β-1 isoform, while they increased the expression of the Tra2β-3 isoform, which is shorter and lacks the N-terminal RS1 domain. Increased expression of Tra2β-3-GFP were shown to interfere with the incorporation of CHEK1 exon 3 into its mature transcript, normally incorporated by Tra2β-1.Predicted loss-of-function variants clustered in the 5' portion of TRA2B cause a new neurodevelopmental syndrome through an apparently dominant negative disease mechanism involving the use of an alternative translation start site and the overexpression of a shorter, repressive Tra2β protein.

Globally, multiple heavy metal contamination is an increasingly common problem. As heavy metals have the potential to disrupt microbially-mediated biogeochemical cycling, it is critical to understand their impact on microbial physiology. However, systems-level studies on the effects of a combination of heavy metals on bacteria are lacking. Here, we use a native Bacillus cereus isolate from the subsurface of the Oak Ridge Reservation (ORR; Oak Ridge, TN, USA) — representing a highly abundant species at the site— to assess the combined impact of eight metal contaminants. Using this metal mixture and individual metals, all at concentrations based on the ORR site geochemistry, we performed growth experiments and proteomic analyses of the B. cereus strain, in combination with targeted MS-based metabolomics and gene expression profiling. The combination of eight metals impacts cell physiology in a manner that could not have been predicted from summing phenotypic responses to the individual metals. Specifically, exposure to the metal mixture elicited global iron starvation responses not observed in any of the individual metal treatments. As nitrate is also a significant contaminant at the ORR site and nitrate and nitrite reductases are iron-containing enzymes, we also examined the effects of the metal mixture on reduction of nitrogen oxides. We found that the metal mixture inhibits the activity of these enzymes through a combination of direct enzymatic damage and post-transcriptional and post-translational regulation. Altogether, these data suggest that metal mixture studies are critical for understanding how multiple rather than individual metals influence microbial processes in the environment.

Multiple heavy metal contamination is an increasingly common global problem. Heavy metals have the potential to disrupt microbially mediated biogeochemical cycling. However, systems-level studies on the effects of combinations of heavy metals on bacteria are lacking. For this study, we focused on the Oak Ridge Reservation (ORR; Oak Ridge, TN, USA) subsurface which is contaminated with several heavy metals and high concentrations of nitrate. Using a native Bacillus cereus isolate that represents a dominant species at this site, we assessed the combined impact of eight metal contaminants, all at site-relevant concentrations, on cell processes through an integrated multi-omics approach that included discovery proteomics, targeted metabolomics, and targeted gene-expression profiling. The combination of eight metals impacted cell physiology in a manner that could not have been predicted from summing phenotypic responses to the individual metals. Exposure to the metal mixture elicited a global iron starvation response not observed during individual metal exposures. This disruption of iron homeostasis resulted in decreased activity of the iron-cofactor-containing nitrate and nitrite reductases, both of which are important in biological nitrate removal at the site. We propose that the combinatorial effects of simultaneous exposure to multiple heavy metals is an underappreciated yet significant form of cell stress in the environment with the potential to disrupt global nutrient cycles and to impede bioremediation efforts at mixed waste sites. Our work underscores the need to shift from single- to multi-metal studies for assessing and predicting the impacts of complex contaminants on microbial systems.

Smith-Kingsmore Syndrome (SKS) is a rare genetic syndrome associated with megalencephaly, a variable intellectual disability, autism spectrum disorder, and MTOR gain of function variants. Only 30 patients with MTOR missense variants are published, including 14 (47%) with the MTOR c.5395G>A p.(Glu1799Lys) variant. Limited phenotypic data impacts the quality of information delivered to families and the robustness of interpretation of novel MTOR missense variation. This study aims to improve our understanding of the SKS phenotype through the investigation of 16 further patients with the MTOR c.5395G>A p.(Glu1799Lys) variant. Through the careful phenotypic evaluation of these 16 patients and integration with data from 14 previously reported patients, we have defined major (100% patients) and frequent (>15%) SKS clinical characteristics and, using these data, proposed guidance for evidence-based management. In addition, in the absence of functional studies, we suggest that the combination of the SKS major clinical features of megalencephaly (where the head circumference is at least 3SD) and an intellectual disability with a de novo MTOR missense variant (absent from population databases) should be considered diagnostic for SKS.

One long-standing theoretical model of shyness proposes that the origins and maintenance of shyness are associated with an approach-avoidance motivational conflict (Asendorpf, 1990), such that shy individuals are motivated to socially engage (high approach motivation) but are too anxious to do so (high avoidance motivation). However, this model has not been empirically tested in predicting the development of shyness. In two separate longitudinal studies, we used the Carver and White (1994) Behavioral Inhibition and Activation System (BIS/BAS) scales as a proxy of approach-avoidance motivations and growth curve analyses to examine whether individual differences in these hypothesized motivational tendencies were associated with the development of shyness across 3 years from late childhood to adolescence (Study 1, N = 1284; 49.8% female, Mage = 10.72, SDage = 1.73, M level of parental education fell between associate's degree/diploma and undergraduate degree) and across nearly a decade from emerging adulthood to young adulthood (Study 2, N = 83; 57.8% females, Mage = 23.56 years, SDage = 1.09 years, 92.8% had at least a high school education). Contrary to the approach-avoidance conflict model of shyness, we found that a combination of high BIS/low BAS, not high BIS/high BAS, was associated with relatively higher shyness contemporaneously and across development in both studies. We discuss the processes that might link individual differences in approach-avoidance motivations to the development of shyness in adolescence and young adulthood. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The authors examined how children's frontal electroencephalogram (EEG) theta/beta ratio-an index of neurocognitive control-changed from baseline to a social stressor, and whether these EEG changes moderated the relation between temperament and anxiety. Children (N = 152; Mage = 7.82 years, 52% male, 81% White) had their EEG recorded during a baseline and speech anticipation condition. Children's frontal theta/beta ratio decreased from baseline to speech anticipation, and this baseline-to-task change moderated the relation between temperamental shyness and social anxiety. Temperamental shyness was related to higher state and trait social anxiety only among children with large baseline-to-task decreases in theta/beta ratio. Findings are consistent with theoretical models hypothesizing that temperamentally shy children with heightened neurocognitive control may be at greater risk for anxiety.

Generation Z (1997–2012) has been characterized in the popular media as more socially inhibited, cautious, and risk averse than prior generations, but are these differences found between generations on an empirical level? And, if so, are these differences observable within generations in response to acute events such as the COVID-19 pandemic? Using a simplified time-lagged design to control for age effects, we examined between-group differences in self-reported shyness in young adult participants ( N = 806, age: 17–25 years) at the same developmental age and university from the millennial generation (tested: 1999–2001; n = 266, Mage = 19.67 years, 72.9% female) and Generation Z (tested: 2018–2020), the latter generation stratified into prepandemic ( n = 263, M = 18.86 years, 82.4% female) and midpandemic ( n = 277, Mage = 18.67 years, 79.6% female) groups. After first establishing measurement invariance to ensure trustworthy group comparisons, we found significantly higher mean levels of shyness across each successive cohort, starting with millennials, through Generation Z before the pandemic, to Generation Z during the pandemic.

Through the use of model studies, an approach was conceived towards the synthesis of the taiwanschirin family of natural products. These are structurally complex compounds which represent highly challenging and biologically active targets for total synthesis. This work describes a successful synthesis of the complex taiwanschirin fused [8,6,5] core through a novel alkynylation reaction coupled with an intramolecular Heck reaction used to construct the 8-membered ring., Key enolate alkynylation and ring closing Heck reactions have been used to make the core of the taiwanschirin natural products.

Described herein is a green, continuous flow process for the synthesis of various aminoimidazoheterocycles, through the Gröebke-Blackburn-Bienaymé reaction (GBBR). This multicomponent procedure combines aminoazines, aldehydes and isocyanides to generate a wide variety of medicinally privileged, aminated imidazoheterocycle architectures. This method is performed in ethanol, using only mineral acid rather than the standard metal-based catalysts typical to the field. These sustainability benefits have been demonstrated even on multigram scale, exemplifying the facile scalability of the procedure. The process also boasts shorter reaction times, wider scope robustness, and improved yields compared to the currently available methods, with no requirement for an aqueous work-up procedure, affording resulting scaffolds of notable relevance, to a range of medicinal targets of academic and industrial interest.

The aim of this study was to evaluate the antibacterial properties of methylsulfonylmethane (MSM) on vancomycin-resistant Enterococcus faecium (VRE). Bacterial proliferation was measured spectropho...