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The formation of condensed phase nucleoprotein assemblies, such as membraneless organelles (MLOs), that contribute to gene regulation and signaling within the cell is garnering widespread attention. A critical technical challenge is understanding how interactions between intrinsically disordered protein (IDP) and nucleic acid molecular components affect liquid–liquid phase separation (LLPS) into nucleoprotein condensates. To better understand the physics of LLPS that drive the formation of biomolecular condensates (known as coacervates), we investigate a model IDP system using a cationic elastin-like polypeptide (ELP), “E3”, that is engineered to phase separate and bind DNA upon coacervate formation. Using mean field Flory–Huggins (FH) theory, we create ternary phase diagrams to quantify DNA component partitioning within discrete protein- and solvent-rich phases across a range of salt and E3 compositions. We suggest a modified FH theory that combines canonical FH interaction parameters with an approximation of the Debye–Hückel theory to predict the strength of E3–DNA interactions and partitioning with a variable salt concentration. Finally, we establish a simple two-step DNA solution separation/purification assay to highlight the potential utility of our system. This model LLPS biopolymer platform represents an important chemical engineering-based contribution to synthetic biology and DNA technologies, with possible implications for origin of life discussions.

We develop a generalized partially additive model to build a single semiparametric risk scoring system for physical activity across multiple populations. A score comprised of distinct and objective physical activity measures is a new concept that offers challenges due to the nonlinear relationship between physical behaviors and various health outcomes. We overcome these challenges by modelling each score component as a smooth term, an extension of generalized partially linear single-index models. We use penalized splines and propose two inferential methods, one using profile likelihood and a nonparametric bootstrap, the other using a full Bayesian model, to solve additional computational problems. Both methods exhibit similar and accurate performance in simulations. These models are applied to the National Health and Nutrition Examination Survey (NHANES) and quantify nonlinear and interpretable shapes of score components for all-cause mortality.

Transient oligomeric intermediates in the peptide or protein aggregation pathway are suspected to be the key toxic species in many amyloid diseases, but deciphering their molecular nature has remained a challenge. Here we show that the strategy of "double-mutant cycles", used effectively in probing protein-folding intermediates, can reveal transient interactions during protein aggregation. It does so by comparing the changes in thermodynamic parameters between the wild type, and single and double mutants. We demonstrate the strategy by probing the possible transient salt bridge partner of lysine 28 (K28) in the oligomeric states of amyloid β-40 (Aβ40), the putative toxic species in Alzheimer's disease. In mature fibrils, the binding partner is aspartate 23. This interaction differentiates Aβ40 from the more toxic Aβ42, where K28's binding partner is the C-terminal carboxylate. We selectively acetylated K28 and amidated the C-terminus of Aβ40, creating four distinct variants. Spectroscopic measurements of the kinetics and thermodynamics of aggregation show that K28 and the C-terminus interact transiently in the early phases of the Aβ40 aggregation pathway. Hydrogen-deuterium exchange mass spectrometry (using a simple analysis method that we introduce here that takes into account the isotopic mass distribution) supports this interpretation. It is also supported by cellular toxicity measurements, suggesting possible similarities in the mechanisms of toxicity of Aβ40 oligomers (which are more toxic than Aβ40 fibrils) and Aβ42. Our results show that double-mutant cycles can be a powerful tool for probing transient interactions during protein aggregation.

Gene fusions have been discussed in the scientific literature since they were first detected in cancer cells in the early 1980s. There is currently no standardized way to denote the genes involved in fusions, but in the majority of publications the gene symbols in question are listed either separated by a hyphen (-) or by a forward slash (/). Both types of designation suffer from important shortcomings. HGNC has worked with the scientific community to determine a new, instantly recognizable and unique separator—a double colon (::)—to be used in the description of fusion genes, and advocates its usage in all databases and articles describing gene fusions.

Stroke is the fifth leading cause of death in the United States and is a leading cause of disability.(1) Extracranial internal carotid artery stenosis is a major cause of ischemic stroke, as it is estimated to cause 8–15% of ischemic strokes.(2,3) It is critical to improve our strategies for stroke prevention and treatment in order to reduce the burden of this disease. Here, we review approaches for the diagnosis and risk-stratification of carotid artery disease as well as interventional strategies for the prevention and treatment of strokes caused by carotid artery disease. Several critical questions in the field remain and are active areas of research. First, medical therapy has evolved significantly since early trials comparing medical therapy with interventional therapies, and patient outcomes while on contemporary medical therapy are unknown. Therefore, the benefit of revascularizing severe carotid artery disease in the current era of medical therapy is also unknown. Second, optimal management of patients with asymptomatic carotid stenosis continues to be a topic of debate. Third, the role of imaging for further risk-stratification of patients using characteristics of carotid plaques continues to be explored. Fourth, an understanding of how the presence of silent infarcts on brain imaging impacts risk-stratification and selection of treatment strategies is needed. Finally, the optimal use of endovascular management strategies for carotid artery disease, including carotid artery stenting and transcarotid artery revascularization, is an active area of investigation.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common therapeutic complication affecting cancer patients’ quality-of-life. We evaluated clinical characteristics, demographics, and lifestyle factors in association with CIPN following taxane treatment. Methods: Data were extracted from the electronic health record of 3387 patients diagnosed with a primary cancer and receiving taxane (i.e., paclitaxel or docetaxel) at Vanderbilt University Medical Center. Neuropathy was assessed via a validated computer algorithm. Univariate and multivariate regression models were applied to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of CIPN-associated factors. Results: Female sex (OR = 1.28, 95% CI = 1.01–1.62), high body-mass index (BMI) (OR = 1.31, 95% CI = 1.06–1.61 for overweight, and OR = 1.49, 95% CI = 1.21–1.83 for obesity), diabetes (OR = 1.66, 95% CI = 1.34–2.06), high mean taxane dose (OR = 1.05, 95% CI = 1.03–1.08 per 10 mg/m2), and more treatment cycles (1.12, 95% CI = 1.10–1.14) were positively associated with CIPN. Concurrent chemotherapy (OR = 0.74, 95% CI = 0.58–0.94) and concurrent radiotherapy (OR = 0.77, 95% CI = 0.59–1.00) were inversely associated with CIPN. Obesity and diabetes both had a stronger association with docetaxel CIPN compared to paclitaxel, although interaction was only significant for diabetes and taxane (p = 0.019). Increased BMI was associated with CIPN only among non-diabetic patients (OR:1.34 for overweight and 1.68 for obesity), while diabetes increased CIPN risk across all BMI strata (ORs were 2.65, 2.41, and 2.15 for normal weight, overweight, and obese, respectively) compared to normal-weight non-diabetic patients (p for interaction = 0.039). Conclusions: Female sex, obesity, and diabetes are significantly associated with taxine-induced CIPN. Further research is needed to identify clinical and pharmacologic strategies to prevent and mitigate CIPN in at-risk patient populations.

Synopsis The mangrove rivulus (Kryptolebias marmoratus) is a phenotypically plastic teleost fish that can spend considerable time on land and traverse the terrestrial realm through a behavior termed the tail-flip jump. The tail-flip jump is a transitional stage between fully aquatic and terrestrial lifestyles. Therefore, understanding this behavior can provide insight into how organisms adapt to new environments over evolutionary time. Studies of K. marmoratus show that terrestrial acclimation and exercise improve tail-flip jumping performance due to muscle remodeling, but the implications of these muscular changes on aquatic locomotion are unknown. In the present study, we hypothesized that (1) terrestrial acclimation and exercise lead to physiological changes, such as changes to muscle fiber type, muscle mass distribution, or body shape, that optimize tail-flip jump distance and endurance while negatively impacting swimming performance in K. marmoratus, and (2) plasticity of the brain (which has been demonstrated in response to a variety of stimuli in K. marmoratus) allows terrestrial emersion and exercise to cause behavioral changes that promote survival and long-term reproductive success. To test these hypotheses, we measured the critical swimming speed (Ucrit), tail-flip jump distance, terrestrial endurance, and undisturbed aquatic behavior of age- and size-matched K. marmoratus before and after a terrestrial exercise period. This period consisted of six 3-min exercise sessions spread over 12 days, during which the fish were prompted to jump continuously. To isolate the effects of air exposure, a separate group was exposed to air for an equivalent period but not allowed to jump. Air exposure improved maximum jump distance but negatively affected swimming performance (Ucrit). Terrestrial endurance (number of jumps) improved in the exercised group, but Ucrit showed no significant change. Contrary to our first hypothesis, a trade-off exists between jump distance and Ucrit but not between jump endurance and Ucrit. Exercised individuals were more active following exercise, resulting either from the onset of dispersion behavior or a heightened stress response.

This protocol quantifies cysteine residues from small amounts of pollen (10 mg) after phenylisothiocyanate (PITC) derivatization (adapted from Manneberg et al 1995). Quantification of cysteine by other methods is difficult because of its instability during amino acid analysis. Samples of anther pollen, corbicular pollen, or stored pollen from bee colonies are completely digested in strong acid. Cysteine residues are completely oxidized to cysteic acid then derivatized with PITC before HPLC UV VIS analysis. Manneberg, M., Lahm, H., & Fountoulakis, M. (1995). Quantification of cysteine residues following oxidation to cysteic acid in the presence of sodium azide. Analytical Biochemistry, 231, 349-353. https://doi.org/10.1006/abio.1995.9988 National Program Number: NP 305 Project Number: 2022-21000-022-000D, 2022-21000-022-053-I Carl Hayden Bee Research Center, USDA-ARS PWA, Tucson, Arizona, USA Grand Challenge - Assessing the Nutrient Contents of Pollen for Bees

Complexes featuring lanthanide-ligand multiple bonds are rare and highly reactive. They are important synthetic targets to understand 4f/5d-bonding in comparison to d-block and actinide congeners. Herein, the isolation and characterization of a bridging cerium(IV)-nitride complex: [(TriNOx)Ce(Li

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype–phenotype correlations in individuals with biallelic SLC18A2 variants. Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype–phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies. Results: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities. Conclusion: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders. © 2022 American College of Medical Genetics and Genomics, National Institutes of Health, NIH: T32 GM007526-42; National Heart, Lung, and Blood Institute, NHLBI; National Human Genome Research Institute, NHGRI: K08 HG008986; National Institute of Neurological Disorders and Stroke, NINDS: R35NS105078; International Rett Syndrome Foundation, IRSF: 3701-1; Muscular Dystrophy Association, MDA: 512848; American Brain Foundation, ABF; American Academy of Neurology, AAN; Takeda Science Foundation, TSF; Japan Agency for Medical Research and Development, AMED: JP22ek0109486, JP22ek0109493, JP22ek0109549; Horizon 2020 Framework Programme, H2020; Muscular Dystrophy UK, MDUK; Multiple System Atrophy Trust, MSAT; Brain Research UK, BRUK; Baylor-Hopkins Center for Mendelian Genomics, BHCMG: UM1 HG006542; Medical Research Council, MRC: G0601943, MR/S005021/1, MR/S01165X/1; Ataxia UK; European Research Council, ERC; Rosetrees Trust; Great Ormond Street Hospital Charity, GOSH; Japan Society for the Promotion of Science, KAKEN: JP19H03621, JP20K07907, JP20K08164, JP20K16932, JP20K17936, JP21k15907; Horizon 2020: 714853, MC-A658-5TY30; University College London Hospitals Biomedical Research Centre, UCLH BRC; King Salman Center for Disability Research, KSCDR: RG-2022-010, We thank the participants and their families for their involvement in this study. This work was supported by the Japan Agency for Medical Research and Development ( AMED ) under grant numbers JP22ek0109486, JP22ek0109549, and JP22ek0109493 (N.Ma.); Japan Society for the Promotion of Science ( JSPS) KAKENHI under grant numbers JP19H03621 (N.Mi.), JP20K07907 (S.M.), JP20K08164 (T.Miz.), JP20K17936 (A.F.), JP20K16932 (K.H.), and JP21k15907 (Y.U.); and the Takeda Science Foundation (T.Miz., N.Mi., and N.Ma.). This study was partially supported by the US National Human Genome Research Institute and National Heart Lung and Blood Institute to the Baylor-Hopkins Center for Mendelian Genomics (UM1 HG006542 to J.R.L.), US National Institute of Neurological Disorders and Stroke (R35NS105078 to J.R.L.), and Muscular Dystrophy Association (512848 to J.R.L.). D.Ma. was supported by a Medical Genetics Research Fellowship Program through the National Institutes of Health (T32 GM007526-42). D.P. was supported by a Clinical Research Training Scholarship in Neuromuscular Disease partnered by the American Academy of Neurology , American Brain Foundation , and Muscle Study Group and by the International Rett Syndrome Foundation (grant number #3701-1). J.E.P. was supported by the National Human Genome Research Institute (K08 HG008986). H.H. was funded by the Medical Research Council ( MRC) (MR/S01165X/1, MR/S005021/1, and G0601943), NIHR University College London Hospitals Biomedical Research Centre , Rosetree Trust, Ataxia UK , Multiple System Atrophy Trust , Brain Research UK , Sparks Great Ormond Street Hospital Charity , Muscular Dystrophy UK , and Muscular Dystrophy Association . N.D. was supported by an MRC strategic award to establish International Centre for Genomic Medicine in Neuromuscular Diseases (MR/S005021/1). This project also received funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement number 714853) and was supported by the Medical Research Council through grant MC-A658-5TY30. We acknowledge the support of King Salman Center for Disability Research through Research Group no RG-2022-010 (F.S.A.). Figure 1A, 2A, and Graphical Abstract were created with BioRender.com ., We thank the participants and their families for their involvement in this study. This work was supported by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP22ek0109486, JP22ek0109549, and JP22ek0109493 (N.Ma.); Japan Society for the Promotion of Science (JSPS) KAKENHI under grant numbers JP19H03621 (N.Mi.), JP20K07907 (S.M.), JP20K08164 (T.Miz.), JP20K17936 (A.F.), JP20K16932 (K.H.), and JP21k15907 (Y.U.); and the Takeda Science Foundation (T.Miz., N.Mi., and N.Ma.). This study was partially supported by the US National Human Genome Research Institute and National Heart Lung and Blood Institute to the Baylor-Hopkins Center for Mendelian Genomics (UM1 HG006542 to J.R.L.), US National Institute of Neurological Disorders and Stroke (R35NS105078 to J.R.L.), and Muscular Dystrophy Association (512848 to J.R.L.). D.Ma. was supported by a Medical Genetics Research Fellowship Program through the National Institutes of Health (T32 GM007526-42). D.P. was supported by a Clinical Research Training Scholarship in Neuromuscular Disease partnered by the American Academy of Neurology, American Brain Foundation, and Muscle Study Group and by the International Rett Syndrome Foundation (grant number #3701-1). J.E.P. was supported by the National Human Genome Research Institute (K08 HG008986). H.H. was funded by the Medical Research Council (MRC) (MR/S01165X/1, MR/S005021/1, and G0601943), NIHR University College London Hospitals Biomedical Research Centre, Rosetree Trust, Ataxia UK, Multiple System Atrophy Trust, Brain Research UK, Sparks Great Ormond Street Hospital Charity, Muscular Dystrophy UK, and Muscular Dystrophy Association. N.D. was supported by an MRC strategic award to establish International Centre for Genomic Medicine in Neuromuscular Diseases (MR/S005021/1). This project also received funding from the European Research Council under the European Union's Horizon 2020 Research and Innovation Program (grant agreement number 714853) and was supported by the Medical Research Council through grant MC-A658-5TY30. We acknowledge the support of King Salman Center for Disability Research through Research Group no RG-2022-010 (F.S.A.). Figure 1A, 2A, and Graphical Abstract were created with BioRender.com.

To determine the prognostic significance of central nervous system (CNS) leukemic involvement in newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL), outcomes on consecutive, phase 3 Children’s Oncology Group clinical trials were examined. AALL0434 and AALL1231 tested efficacy of novel agents within augmented-Berlin-Frankfurt-Münster (aBFM) therapy. In addition to testing study-specific chemotherapy through randomization, the AALL0434 regimen delivered cranial radiation therapy (CRT) to most participants (90.8%), whereas AALL1231 intensified chemotherapy to eliminate CRT in 88.2% of participants. In an analysis of 2164 patients with T-ALL (AALL0434, 1550; AALL1231, 614), 1564 had CNS-1 (72.3%), 441 CNS-2 (20.4%), and 159 CNS-3 (7.3%). The 4-year event-free-survival (EFS) was similar for CNS-1 (85.1% ± 1.0%) and CNS-2 (83.2% ± 2.0%), but lower for CNS-3 (71.8% ± 4.0%; P = .0004). Patients with CNS-1 and CNS-2 had similar 4-year overall survival (OS) (90.1% ± 0.8% and 90.5% ± 1.5%, respectively), with OS for CNS-3 being 82.7% ± 3.4% (P = .005). Despite therapeutic differences, outcomes for CNS-1 and CNS-2 were similar regardless of CRT, intensified corticosteroids, or novel agents. Except for significantly superior outcomes with nelarabine on AALL0434 (4-year disease-free survival, 93.1% ± 5.2%), EFS/OS was inferior with CNS-3 status, all of whom received CRT. Combined analyses of >2000 patients with T-ALL identified that CNS-1 and CNS-2 status at diagnosis had similar outcomes. Unlike B-ALL, CNS-2 status in T-ALL does not impact outcome with aBFM therapy, without additional intrathecal therapy, with or without CRT. Although nelarabine improved outcomes for those with CNS-3 status, novel approaches are needed. These trials were registered at www.clinicaltrials.gov as #NCT00408005 (AALL0434) and #NCT02112916 (AALL1231).

The dynamics of muscle activation during fast visually guided reaching are suggestive of two neural control signals; an early signal that acts at “express” latencies in response to the visual stimulus, and a longer latency signal that executes a strategic reach plan. Here we developed a task designed to temporally isolate the express visuomotor response from the longer latency muscle response, and to characterize the time course of corticospinal excitability changes in the express response time window when the late voluntary response is delayed. We tested this by measuring electromyograms (EMG) and changes in Motor Evoked Potential (MEP) amplitudes following Transcranial Magnetic Stimulation (TMS) of the motor cortex, as participants reached either towards or away from visual targets. Crucially, the information about the task rule was provided by the luminance of the target itself, and so was unknown to the subject until the instant of target presentation. This feature delayed reaction times, likely because additional (presumably cortical) processing was required to interpret and apply the rule before formation of a goal directed reach plan. The earliest EMG responses to target presentation occurred with a 70-105 ms time window, and were oriented to bring the hand toward the location of the target. However, there was also a slightly later response that was also time-locked to target appearance in a 105-140 ms time window. This second response was “reciprocal” to the first, such that it was oriented to take the hand in the direction opposite from the target. In some participants, additional oscillating cycles were apparent after the first two target-related responses. These multiphasic express visuomotor responses were nearly identical in both pro- and anti-reach conditions. These muscle activity responses were generally reflected in the temporal pattern of corticospinal excitability modulations in experiment two. Indeed, the MEP and background EMG responses showed an alternating pattern similar to that in experiment one, although the effect was clearer in the anti-reach than the pro-reach condition. Overall, the data show that the express and voluntary responses are indeed distinct neural control signals, which supports the hypothesis that at least two separate neural pathways (one slow and one fast) contribute to the control of visually guided reaching. The properties of the fast pathway are consistent with a tecto-reticulospinal pathway, while those of the slow pathway are consistent with a transcortical loop.

This protocol quantifies total protein contents of small amounts of pollen (10 mg) using the bicinchoninic acid (BCA) assay of the Pierce BCA protein assay kit (Thermo Scientific product number 23225). This protocol adapts the kit protocol for analysis of anther pollen, corbicular pollen, and stored pollen from bee colonies. Pollen samples are subjected to acid hydrolysis to digest refractory proteins and to degrade sugars and other pollen substances that interfere with total protein assays. The acid hydrolysis releases substantially more protein from pollens than occurs with soluble proteins but may result in some protein losses due to the harsh acidic conditions. Similar BCA analysis methods without hydrolysis may be used to quantify soluble proteins (proteins obtained without acid hydrolysis or other digest methods) which may exclude insoluble pollen proteins from full quantification. The total protein contents obtained using BCA analysis of acid hydrosylates represents the maximum protein available to consumers and likely includes some refractory proteins that may not be digested by the consumer. The assay is modified from the original standard protocol to work for pollen analysis: Document Connect (thermofisher.com). Please note that our steps differ from the commercial source protocol. National Program Number: NP 305 Project Number: 2022-21000-022-000D, 2022-21000-022-053-I Carl Hayden Bee Research Center, USDA-ARS PWA, Tucson, Arizona, USA Grand Challenge - Assessing the Nutrient Contents of Pollen for Bees

During visually guided reaching, proximal limb muscles can be activated within 80 ms of target appearance. Such “express” visuomotor responses are temporally aligned with target appearance rather than movement onset, and invariably tuned towards the direction of the visual target regardless of the instructed reach direction. These features prompt the hypothesis that express visuomotor responses are driven by a subcortical pathway. We tested this by measuring the changes in Motor Evoked Potential (MEP) size following Transcranial Magnetic Stimulation (TMS) or Transcranial Electrical Stimulation (TES) of the motor cortex, as participants reached either towards or away from visual targets. We found that 70-80 ms after target presentation, MEPs in a primary shoulder flexor muscle (pectoralis major) were oriented towards the target direction regardless of whether the participant subsequently reached towards or away from the target. Similar target-oriented MEP modulations occurred in posterior deltoid and biceps brachii muscles, whereas MEPs in a finger muscle were affected neither by target nor reach direction. Critically, there were no significant differences in modulation of responses to TMS versus TES across all reaching conditions, which suggests that the target-oriented modulation occurs downstream of the motor cortex output neurons. Combined, our results are consistent with a subcortical rather than cortical origin for the earliest changes in corticospinal excitability following visual target onset. A prime candidate for such subcortical modulation includes the superior colliculus and reticular formation.

This protocol uses FAME (Fatty Acid Methyl Esterification) techniques adapted from Seppanen-Laasko et al., 2002 to quantify fatty acid contents in small samples (10 mg) of anther pollen, corbicular pollen, or stored pollen. Pollen is initially fractured by cell disruption and fatty acids are extracted by Folch extraction/partition. Fatty acids are converted to their fatty acid methyl ester (FAME) equivalents by acid methylation then separated and analyzed by GCMS in SIM mode. Seppänen-Laasko, T., Laakso, I., & Hiltunen, R. (2002). Analysis of fatty acids by gas chromatography and its relevance to research on health and nutrition. Analytica Chimica Acta, 465, 39-62. https://doi.org/10.1016/S0003-2670(02)00397-5 National Program Number: NP 305 Project Number: 2022-21000-022-000D, 2022-21000-022-053-I Carl Hayden Bee Research Center, USDA-ARS PWA, Tucson, Arizona, USA Grand Challenge - Assessing the Nutrient Contents of Pollen for Bees

This protocol quantifies total lipid contents of pollen through colorimetric oxidation of lipids by chromic acid (adapted from Amenta, 1970). Small pollen samples (10 mg) are fractured by cell homogenization and lipids are extracted by Folch extraction. Lipid amounts are measured by colorimetric changes when hexavalent (+6 oxidation state) chromium ion is reduced to a trivalent (+3 oxidation state) state during lipid oxidation. The accuracy of the assay depends on how thoroughly the initial extraction excludes non-lipid compounds such as sugars and proteins. A considerable drawback of this method is the toxicity, carcinogenicity, and environmental toxicity of the hexavalent chromium reagents used in this assay. Amenta, J.S. (1970). A rapid extraction and quantification of total lipids and lipid fractions in blood and feces. Clinical Chemistry, 16, 339-346. National Program Number: NP 305 Project Number: 2022-21000-022-000D, 2022-21000-022-053-I Carl Hayden Bee Research Center, USDA-ARS PWA, Tucson, Arizona, USA Grand Challenge - Assessing the Nutrient Contents of Pollen for Bees

Chylous pericardial effusions are extremely rare outside of thoracic and cardiac surgery patients. We report the case of an 8-year-old girl with history of recurrent benign giant cell granulomas who developed a large chylous pericardial effusion with cardiac tamponade soon after beginning therapy with imatinib. In this article, we discuss the presentation, diagnosis, and management and review the published literature of this rarely reported side effect of this medication.

Decarbonylation along with P-atom transfer from the phosphaethynolate anion, PCO

Objective: We examined whether neuropsychological function in ADHD can be improved by the New Forest Parenting Programme (NFPP), that combines standard parenting strategies with self-regulatory skills training, or predict ADHD and quality of life (QoL) treatment effects. Method: Participants were 93 medication-naive preschool children with ADHD (3–7 years) randomized to either NFPP ( n = 49) or treatment as usual (TAU; n = 44) in a recent randomized trial. Laboratory measures of executive function, reaction time variability, and delay of gratification were collected along with parent ratings of ADHD and QoL at baseline and post treatment. Ratings were collected again at 3-month follow-up. Results: NFPP did not improve neuropsychological function (compared to TAU), and baseline neuropsychological function did not predict treatment-related ADHD or QoL effects. Conclusion: Although NFPP includes a neuropsychological training element and has been shown to improve several clinical outcomes, it did not improve the neuropsychological functions it targets.

Psychosocial factors are associated with the achievement of optimal cardiovascular disease risk factor (CVDRF) levels. To date, little research has examined multiple psychosocial factors simultaneously to identify distinguishing psychosocial profiles among individuals with CVDRF. Further, it is unknown whether profiles are associated with achievement of CVDRF levels longitudinally. Therefore, we characterized psychosocial profiles of individuals with CVDRF and assessed whether they are associated with achievement of optimal CVDRF levels over 15 years. We included 1,148 CARDIA participants with prevalent hypertension, hypercholesterolemia and/or diabetes mellitus in 2000–2001. Eleven psychosocial variables reflecting psychological health, personality traits, and social factors were included. Optimal levels were deemed achieved if: Hemoglobin A1c (HbA1c) < 7.0%, low-density lipoprotein (LDL) cholesterol < 100 mg/dl, and systolic blood pressure (SBP) < 140 mm Hg. Latent profile analysis (LPA) revealed three psychosocial profile groups “Healthy”, “Distressed and Disadvantaged” and “Discriminated Against”. There were no significant differences in achievement of CVDRF levels of the 3 targets combined across profiles. Participants in the “Distressed and Disadvantaged” profile were less likely to meet optimal HbA1c levels compared to individuals in the “Healthy” profile after demographic adjustment. Associations were attenuated after full covariate adjustment. Distinct psychosocial profiles exist among individuals with CVDRF, representing meaningful differences. Implications for CVDRF management are discussed.

A low-spin and mononuclear vanadium complex, ((Me)nacnac)V(CO)(η(2)–P≡C(t)Bu) (2) ((Me)nacnac(−) = [ArNC(CH(3))](2)CH, Ar = 2,6-(i)Pr(2)C(6)H(3)), was prepared upon treatment of the vanadium neopentylidyne complex ((Me)nacnac)V≡C(t)Bu(OTf) (1) with Na(OCP)(diox)(2.5) (diox = 1,4-dioxane) while the isoelectronic ate-complex [Na(15–crown–5)]{([ArNC(CH(2))]CH[C(CH(3))NAr])V(CO)(η(2)–P≡C(t)Bu)} (4), was obtained via the reaction of Na(OCP)(diox)(2.5) and ([ArNC(CH(2))]CH[C(CH(3))NAr])V≡C(t)Bu(OEt(2)) (3) in the presence of crown–ether. Computational studies suggest the P–atom transfer to proceed by [2+2]–cycloaddition of the P≡C bond across the V≡C(t)Bu moiety, followed by a reductive decarbonylation to form V–C≡O linkage. The nature of the electronic ground state in diamagnetic complexes, 2 and 4, was further investigated both theoretically and experimentally, using a combination of Density Functional Theory (DFT) calculations, UV-Vis and NMR spectroscopies, cyclic voltammetry, X-ray Absorption Spectroscopy (XAS) measurements, and comparison of salient bond metrics derived from X-ray single-crystal structural characterization. In combination, these data are consistent with a low-valent vanadium ion in complexes 2 and 4. This study represents the first example of a metathesis reaction between the P-atom of [PCO](‒) and an alkylidyne ligand.

Intestinal transplantation is a therapeutic treatment option for patients with irreversible intestinal failure. The presence of donor-specific antibodies (DSAs) has been associated with increased antibody-mediated rejection and allograft loss for recipients of all the solid organ transplants. This case report describes the posttransplant course in the first year of a patient who received a T-cell and B-cell flow cross-match (FXM) and complement-dependent cytotoxicity cross-match positive intestinal transplant in the presence of several class I and class II DSAs who underwent a “temporary desensitization” using the donor spleen. The temporary donor splenic transplant removed several class I and II DSAs as demonstrated by the negative subsequent T-cell FXM, the decreased mean channel shift of the positive B-cell FXM with a significant decrease in DSA mean florescence intensity post temporary splenic transplant. The patient experienced an isolated incidence of acute rejection, which responded to therapy. He had no infectious or cancerous sequelae from the immunosuppression modalities. He was able to discontinue total parenteral nutrition and gained weight after the procedure. Long-term effects are not able to be determined from this approach; hence, further research is warranted to better evaluate the real efficacy of this strategy.

How to translate insights gained from studies in one organismal species for what is most likely to be germane in another species, such as from mice to humans, is a ubiquitous challenge in basic biology as well as biomedicine. This is an especially difficult problem when there are few molecular features that are obviously important in both species for a given phenotype of interest. Neuropathologies are a prominent realm of this complication. Schizophrenia is complex psychiatric disorder that affects 1% of the population. Many genetic factors have been proposed to drive the development of schizophrenia, and the 22q11 microdeletion (MD) syndrome has been shown to dramatically increase this risk. Due to heterogeneity of presentation of symptoms, diagnosis and formulation of treatment options for patients can often be delayed, and there is an urgent need for novel therapeutics directed toward the treatment of schizophrenia. Here, we present a novel computational approach, Translational Pathways Classification (TransPath-C), that can be used to identify shared pathway dysregulation between mouse models and human schizophrenia cohorts. This method uses variation of pathway activation in the mouse model to predict both mouse and human disease phenotype. Analysis of shared dysregulated pathways called out by both the mouse and human classifiers of TransPath-C can identify pathways that can be targeted in both preclinical and human cohorts of schizophrenia. In application to the 22q11 MD mouse model, our findings suggest that PAR1 pathway activation found upregulated in this mouse phenotype is germane for the corresponding human schizophrenia cohort such that inhibition of PAR1 may offer a novel therapeutic target.

This commentary characterises as an insurgency those elements of the Food Industry seeking to retain and expand industry profit-making opportunity with scant regard to the effect on public health and wellbeing. Premised on a conflict in which the battlespace encompasses the drivers of (un)healthful behaviour, our view encourages opponents of Food Industry methods to consider an approach based on analogy of successful Counter-Insurgency strategies to a health promotion context.

Controversy remains about whether exercise-induced muscle damage (EIMD) and the subsequent repeated bout effect (RBE) are caused by the stretching of an activated muscle, or the production of high force at long, but constant, muscle lengths. The aim of this study was to determine the influence of muscle fascicle stretch elicited during different muscle contraction types on the magnitude of EIMD and the RBE. Fourteen participants performed an initial bout of lower limb exercise of the triceps surae. One leg performed sustained static contractions at a constant long muscle length (ISO), whereas the contralateral leg performed a bout of eccentric heel drop exercise (ECC). Time under tension was matched between the ECC and ISO conditions. Seven days later, both legs performed ECC. Plantar flexor twitch torque, medial gastrocnemius (MG) fascicle length and muscle soreness were assessed before, 2 h and 2 days after each exercise bout. MG fascicle length and triceps surae surface electromyography were examined across the bouts of exercise. We found that both ECC and ISO conditions elicited EIMD and a RBE. ISO caused less damage 2 h after the initial bout (14% less drop in twitch torque, P = 0.03) and less protection from soreness 2 days after the repeated bout (56% higher soreness, P = 0.01). No differences were found when comparing neuromechanical properties across exercise bouts. For MG, the action of stretching an active muscle seems to be more important for causing damage than a sustained contraction at a long length.

Oxidation of the low-spin FeIV imido complex [{(tBupyrr)2py}Fe═NAd] (1) ((tBupyrr)2py2- = 2,6-bis(3,5-di-tert-butyl-pyrrolyl)pyridine, Ad = 1-adamantyl) with AgOAc or AgNO3 promotes reductive N-N bond coupling of the former imido nitrogen with a pyrrole nitrogen to form the respective ferric hydrazido-like pincer complexes [{(tBupyrrNAd)(tBupyrr)py}Fe(κ2-X)] (X = OAc-, 2OAc; NO3-, 2NO3). Reduction of 2OAc with KC8 cleaves the N-N bond to reform the FeIV imido ligand in 1, whereas acid-mediated demetalation of 2OAc or 2NO3 yields the free hydrazine ligand [(tBupyrrNHAd)(tBupyrrH)py] (3), the latter of which can be used as a direct entry to the iron imido complex when treated with [Fe{N(SiMe3)2}2]. In addition to characterizing these Fe systems, we show how this nitrene transfer strategy can be expanded to Co for the one-step synthesis of Co{(tBu-NHAdpyrr)(tBupyrr)py}] (4) ((tBu-NHAdpyrr)(tBupyrr)py2- = 2-(3-tBu-5-(1-adamantylmethyl-2-methylpropane-2-yl)-pyrrol-2-yl)-6-(3,5-tBu2-pyrrol-2-yl)-pyridine).

Drug checking is an evidence-based strategy for overdose prevention that continues to operate (where it operates) in a legal “gray zone” due to the legal classification of some drug checking tools as drug paraphernalia—the purview of law enforcement, not public health. This article takes the emergence of fentanyl in the U.S. drug supply as a starting point for examining two closely related questions about drug checking and drug market expertise. First, how is the epistemic authority of law enforcement over the material realities of the drug market produced? Second, in the context of that authority, what are the socio-political implications of technologically advanced drug checking instruments in the hands of people who use drugs? The expertise that people who use drugs maintain about the nature of illicit drug market and how to navigate the illicit drug supply has long been discounted as untrustworthy, irrational, or otherwise invalid. Yet, increased access to drug checking tools has the potential to afford the knowledge produced by people who use drugs a technological validity it has never before enjoyed. In this article, I engage with theories of knowledge production and ontological standpoint from the field of science, technology, and society studies to examine how law enforcement produces and maintains epistemic authority over the illicit drug market and to explore how drug checking technologies enable new forms of knowledge production. I argue that drug checking be viewed as a form of social resistance against law enforcement’s epistemological authority and as a refuge against the harms produced by drug criminalization.