2,3‐Butanediol (BDO) is a bio‐derived building block available from biomass through biochemical methods in high titers (>120 g L−1) making it an attractive target for production and further upgrading ...to chemical products and fuels such as sustainable aviation fuel. A key challenge to enable the adoption of BDO as a precursor is the effective separation and isolation of this molecule from the fermentation broth. 2,3‐Butanediol has a boiling point higher than that of water (177°C), and as a consequence, separation via distillation methods is an energy‐intensive and therefore costly approach. We have improved the BDO separation through conversion to a 1,3‐dioxolane directly in fermentation broth via reaction with bio‐derived aldehydes catalyzed by a solid acid catalyst. The resulting dioxolane phase separates from the fermentation broth, allowing for easy decantation and isolation in >90% isolated yield. Isolated dioxolane can be used directly as a compression iginition fuel, trans‐acetalized to recover high‐purity BDO or used directly in a catalytic process as a BDO synthon to produce methyl ethyl ketone with aldehyde recovery in near quantitative yield.
Online research methods are increasingly used in conservation science to monitor and collect data on online wildlife trade. Shark‐like rays (Rhinopristiformes) are among the most threatened ...vertebrates, prized for their high‐value fins while other uses for their derivatives are largely unrecognized in the literature. The bowmouth guitarfish (Rhina ancylostomus) is characterized by ridges of enlarged thorns, sometimes sold as amulets. Listed on the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) Appendix II, the thorn‐market has been ignored and undocumented. Using systematic, retrospective online searches, we recorded 977 bowmouth‐derivatives for sale. In our global and multi‐lingual scope, 97% of products were offered from Thailand, despite prohibited trade. 98% of all products were thorns (USD3‐300) and sold alongside high‐profile CITES‐listed taxa (e.g., tiger claws). Consistent advertisements from 2012 revealed a previously unquantified trade of an often‐neglected marketplace in elasmobranch research. Our findings offer insight into the drivers of the thorn trade, potentially rooted in cultural beliefs. Our accessible research methods can be applied internationally and across species, providing quantitative and qualitative insights on aspects of the wildlife trade of a critically endangered fish. Continued monitoring of online markets, like this study, is necessary to fill critical gaps for informed policy and species‐specific management.
The Biological Reference Repository (BioR) is a toolkit for annotating variants. BioR stores public and user-specific annotation sources in indexed JSON-encoded flat files (catalogs). The BioR ...toolkit provides the functionality to combine and retrieve annotation from these catalogs via the command-line interface. Several catalogs from commonly used annotation sources and instructions for creating user-specific catalogs are provided. Commands from the toolkit can be combined with other UNIX commands for advanced annotation processing. We also provide instructions for the development of custom annotation pipelines.
The package is implemented in Java and makes use of external tools written in Java and Perl. The toolkit can be executed on Mac OS X 10.5 and above or any Linux distribution. The BioR application, quickstart, and user guide documents and many biological examples are available at http://bioinformaticstools.mayo.edu.
There is a paucity of information regarding financial trends in orthopedic upper extremity surgery. If progress is to be made in advancing agreeable reimbursement models, a more comprehensive ...understanding of these trends is needed. The purpose of this study was to assess national and geographic trends in Medicare reimbursement rates for shoulder and elbow surgical procedures over the past 2 decades.
The 10 most billed Common Procedural Terminology (CPT) codes for both orthopedic shoulder surgery and elbow/upper arm surgery were determined. Medicare reimbursement data for these CPT codes were compiled between 2000 and 2020 and adjusted for inflation. The percentage change for each procedure and the average change in reimbursement each year were analyzed. Data from 2000, 2010, and 2020 were organized by state. The total percent change in physician fee and the percent change per year were tabulated for each CPT code using inflation-adjusted data and averaged by state.
From 2000 to 2020, when corrected for inflation, shoulder and elbow procedures decreased on average by 29.3% and 24.5%, respectively. Shoulder procedures experienced a greater numerical yet statistically insignificant decline in mean reimbursement percent decrease (P = .16), average percent decrease per year (P = .11), a more negative compound annual growth rate (P = .14), and a greater R-squared value as compared with elbow and upper arm procedures. For shoulder procedures, the average percent difference in inflation-adjusted Medicare reimbursement rates from 2000 to 2020 varied from −22.6% in Alaska to −34.1% in Michigan; division data varied from −27.8% in the Mountain Division to −31.2% in the East North Central Division; and region data varied from −28.3% in the West to −30.5% in the Northeast. For elbow and upper arm procedures, the average percent difference in inflation-adjusted Medicare reimbursement rates from 2000 to 2020 varied from −17.6% in Alaska to −29.8% in Michigan; division data varied from −23.0% in the Mountain Division to −26.7% in the East North Central Division; and region data varied from −23.5% in the West to −25.7% in the Northeast.
Inflation-adjusted Medicare reimbursement in upper extremity surgery has decreased markedly between 2000 and 2020. The degree of decrease varies geographically. If access to quality and sustainable surgical orthopedic care is to persist in the United States, increased awareness of these trends is important. The trends identified in this study can serve to customize regional health care policymaking.
Environmental and psychological stressors can adversely affect astronaut cognitive performance in space. This study used a 6° head-down tilt bed rest (HDBR) paradigm to simulate some of the ...physiologic changes induced by microgravity. Twenty-four participants (mean ± SD age 33.3 ± 9.2 years,
= 16 men) spent 60 consecutive days in strict HDBR. They were studied in three groups of eight subjects each. One group served as Control, whereas the other two groups received either a continuous or intermittent artificial gravity (AG) countermeasure of 30 min centrifugation daily (1
acceleration at the center of mass and 2
at the feet). Participants performed all 10 tests of NASA's Cognition battery and a brief alertness and mood survey repeatedly before, during, and after the HDBR period. Test scores were adjusted for practice and stimulus set difficulty effects. A modest but statistically significant slowing across a range of cognitive domains was found in all three groups during HDBR compared to baseline, most consistently for sensorimotor speed, whereas accuracy was unaffected. These changes were observed early during HDBR and did not further worsen or improve with increasing time in HDBR, except for emotion recognition performance. With increasing time spent in HDBR, participants required longer time to decide which facial emotion was expressed. They were also more likely to select categories with negative valence over categories with neutral or positive valence. Except for workload, which was rated lower in the Control group, continuous or intermittent AG did not modify the effect of HDBR on cognitive performance or subjective responses. Participants expressed several negative survey responses during HDBR relative to baseline, and some of the responses further deteriorated during recovery, which highlights the importance of adequate medical and psychological support during extended duration HDBR studies. In conclusion, 60 days of HDBR were associated with moderate cognitive slowing and changes in emotion recognition performance, but these effects were not mitigated by either continuous or intermittent exposure to AG for 30 min daily.
Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our ...objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8-21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk. Schizophrenia polygenic risk was estimated for each participant based on summary statistics from the most recent schizophrenia genome-wide association analysis (Psychiatric Genomics Consortium 2014). After correction for multiple comparisons, greater schizophrenia polygenic risk was significantly associated with reduced speed of emotion identification and verbal reasoning. These associations were significant by age 9 years and there was no evidence of interaction between schizophrenia polygenic risk and age on neurocognitive performance. We then looked at the association between schizophrenia polygenic risk and emotion identification speed in the Harvard/MGH Brain Genomics Superstruct Project sample (695 participants ages 18-35 years), where we replicated the association between schizophrenia polygenic risk and emotion identification speed. These analyses provide evidence for a replicable association between polygenic risk for schizophrenia and a specific aspect of social cognition. Our findings indicate that individual differences in genetic risk for schizophrenia are linked with the development of aspects of social cognition and potentially verbal reasoning, and that these associations emerge relatively early in development.
The topography of Neptune’s large icy moon Triton could reveal important clues to its internal evolution, but has been difficult to determine. New global digital color maps for Triton have been ...produced as well as topographic data for <40% of the surface using stereogrammetry and photoclinometry. Triton is most likely a captured Kuiper Belt dwarf planet, similar though slightly larger in size and density to Pluto, and a likely ocean moon that exhibited plume activity during Voyager 2′s visit in 1989. No surface features or regional deviations of greater than ±1 km amplitude are found. Volatile ices in the southern terrains may take the form of extended lobate deposits 300–500 km across as well as dispersed bright materials that appear to embay local topography. Limb hazes may correlate with these deposits, indicating possible surface–atmosphere exchange. Triton’s topography contrasts with high relief up to 6 km observed by New Horizons on Pluto. Low relief of (cryo)volcanic features on Triton contrasts with high-standing massifs on Pluto, implying different viscosity materials. Solid-state convection occurs on both and at similar horizontal scales but in very different materials. Triton’s low relief is consistent with evolution of an ice shell subjected to high heat flow levels and may strengthen the case of an internal ocean on this active body.
The longer emission wavelengths of red fluorescent proteins (RFPs) make them attractive for whole-animal imaging because cells are more transparent to red light. Although several useful RFPs have ...been developed using directed evolution, the quest for further red-shifted and improved RFPs continues. Herein, we report a structure-based rational design approach to red-shift the fluorescence emission of RFPs. We applied a combined computational and experimental approach that uses computational protein design as an in silico prescreen to generate focused combinatorial libraries of mCherry mutants. The computational procedure helped us identify residues that could fulfill interactions hypothesized to cause red-shifts without destabilizing the protein fold. These interactions include stabilization of the excited state through H-bonding to the acylimine oxygen atom, destabilization of the ground state by hydrophobic packing around the charged phenolate, and stabilization of the excited state by a π-stacking interaction. Our methodology allowed us to identify three mCherry mutants (mRojoA, mRojoB, and mRouge) that display emission wavelengths >630 nm, representing red-shifts of 20–26 nm. Moreover, our approach required the experimental screening of a total of ∼5,000 clones, a number several orders of magnitude smaller than those previously used to achieve comparable red-shifts. Additionally, crystal structures of mRojoA and mRouge allowed us to verify fulfillment of the interactions hypothesized to cause red-shifts, supporting their contribution to the observed red-shifts.
Overexpression of the epidermal growth factor receptor has been demonstrated in advanced prostate cancer and is associated with a poor outcome. A multi-institutional, randomized, phase II study was ...undertaken by the National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of two doses of oral gefitinib in patients with minimally symptomatic, hormone-refractory prostate cancer (HRPC).
Between July and November 2001, 40 patients with HRPC and increasing prostate-specific antigen (PSA) or progression in measurable disease who had not received prior chemotherapy were randomly assigned to 250 mg (n = 19) or 500 mg (n = 21) oral gefitinib daily continuously. The primary end points were PSA response rate and objective measurable response. Functional Assessment of Cancer Therapy Prostate Cancer Subscale (FACT-P) quality-of-life questionnaires were completed at baseline and during treatment.
None of the patients demonstrated a PSA or objective measurable response. Five (14.3%) of 35 assessable patients had stable PSA (one patient at 250 mg and four patients at 500 mg), and five patients (14.3%) had a best response of stable disease (duration, 2.5 to 16.8 months). No significant effect on the rate of increase in PSA was seen. The most common drug-related nonhematologic toxicities observed were grade 1 to 2 diarrhea (250 mg, 65%; 500 mg, 56%), fatigue (250 mg, 29%; 500 mg, 33%), and grade 1 to 2 skin rash (250 mg, 24%; 500 mg, 39%). FACT-P scores decreased during treatment, indicating worsening of symptoms compared with baseline.
Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC.
Autophagy is a highly conserved evolutionary survival or defence process that enables cells and organisms to survive periods of environmental stress by breaking down cellular organelles and ...macromolecules in autolysosomes to provide a supply of nutrients for cell maintenance. However, autophagy is also a part of normal cellular physiology that facilitates the turnover of cellular constituents under normal conditions: it can be readily augmented by mild environmental stress; but becomes dysfunctional with severe oxidative stress leading to cellular pathology. The molluscan hepatopancreas or digestive gland provides a versatile and environmentally relevant model to investigate lysosomal autophagy and stress-induced dysfunctional autophagy. This latter process has been implicated in many animal and human disease conditions, including degenerative and neurodegenerative diseases, as well as obesity related conditions. Many environmental pollutants have also been found to induce dysfunctional autophagy in molluscan hepatopancreatic digestive cells, and in this study, the marine blue mussel Mytilus galloprovincialis was exposed for 7 days to: 0.1 μM, 1 μM and 10 μM concentrations of fluoranthene and phenanthrene (PAHs); chlorpyrifos and malathion (organophosphorus compounds); atrazine (triazine herbicide); copper (transition metal) and dodecylbenzene sulphonic acid (LAS, surfactant). The marine snail or periwinkle, Littorina littorea, was also exposed to phenanthrene, chlorpyrifos and copper. Indices of oxidative stress, cell injury and dysfunctional autophagy were measured (i.e., lysosomal membrane stability, protein carbonyls, lipofuscin, and lysosomal accumulation of lipid or lipidosis). Evidence of oxidative stress, based on the elevation of lipofuscin and protein carbonyls, was found for all compounds tested; with chlorpyrifos being the most toxic to both species. Dysfunctional autophagy was induced by all of the compounds tested in both species, except for atrazine in mussels. This failure of normal autophagy was consistently associated with oxidative stress. Autophagic dysfunction is an important emerging feature in the aetiology of many disease conditions in animals and humans; and an explanatory conceptual mechanistic model has been developed for dysregulation of autophagy in response to oxidative stress.
•Dysfunctional autophagy as a pathological reaction to chemically induced stress appears to be a widespread phenomenon.•Dysfunctional autophagy is characteristic of a number of animal and human diseases, including neurodegenerative diseases.•Some of these disease conditions have been linked to uptake of harmful nanoscale materials derived from road traffic.
Oxidative stress was induced by a range of contaminants in two marine molluscs resulting in dysfunctional lysosomal autophagy in digestive gland cells.
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