The relationship between objective and subjective executive function in Parkinson's disease.

INTRODUCTION: Difficulties in executive functioning (EF) are common in PD; however, the relationship between subjective and objective EF is unclear. Understanding this relationship could help guide clinical EF assessment. This study examined the relationship between subjective self-reported EF (SEF) and objective EF (OEF) and predictors of SEF-OEF discrepancies in PD. METHOD: One-hundred and sixteen non-demented PD participants completed measures of OEF (i.e. problem-solving, cognitive flexibility, inhibition, and working memory) and SEF (Frontal Systems Behavior Scale-Self Executive Dysfunction Subscale). Pearson bivariate correlations and linear regressions were performed to examine the relationship between SEF and OEF and the non-motor symptoms (e.g. mood, fatigue), demographic, and PD characteristic (e.g. MCI status) predictors of discrepancies between OEF and SEF (|OEF minus SEF scores|). Correlates of under-, over-, and accurate-reporting were also explored. RESULTS: Greater SEF complaints and worse OEF were significantly associated (ß =.200, p = .009) and 64% of participants accurately identified their level of OEF abilities. Fewer years of education and greater symptoms of depression, anxiety, and fatigue significantly correlated with greater discrepancies between OEF and SEF. Fatigue was the best predictor of EF discrepancy in the overall sample (ß = .281, p = .022). Exploratory analyses revealed apathy and fatigue associated with greater under-reporting, while anxiety associated with greater over-reporting. CONCLUSIONS: SEF and OEF are significantly related in PD. Approximately 64% of non-demented persons with PD accurately reported their EF skill level, while 28% under-reported and 8% over-reported. SEF-OEF discrepancies were predicted by fatigue in the overall sample. Preliminary evidence suggests reduced apathy and fatigue symptoms relate to more under-reporting, while anxiety relates to greater over-reporting. Given the prevalence of these non-motor symptoms in PD, it is important to carefully consider them when assessing EF in PD.

Morphological and Molecular Identification of Ulva spp. (Ulvophyceae; Chlorophyta) from Algarrobo Bay, Chile: Understanding the Composition of Green Tides.

Green algae blooms of the genus Ulva are occurring globally and are primarily attributed to anthropogenic factors. At Los Tubos beach in Algarrobo Bay along the central Chilean coast, there have been blooms of these algae that persist almost year-round over the past 20 years, leading to environmental, economic, and social issues that affect the local government and communities. The objective of this study was to characterize the species that form these green tides based on a combination of ecological, morpho-anatomical, and molecular information. For this purpose, seasonal surveys of beached algal fronds were conducted between 2021 and 2022. Subsequently, the sampled algae were analyzed morphologically and phylogenetically using the molecular markers ITS1 and tufA, allowing for the identification of at least five taxa. Of these five taxa, three (U. stenophylloides, U. uncialis, U. australis) have laminar, foliose, and distromatic morphology, while the other two (U. compressa, U. aragoensis) have tubular, filamentous, and monostromatic fronds. Intertidal surveys showed that U. stenophylloides showed the highest relative coverage throughout the seasons and all intertidal levels, followed by U. uncialis. Therefore, we can establish that the green tides on the coast of Algarrobo in Chile are multispecific, with differences in relative abundance during different seasons and across the intertidal zone, opening opportunities for diverse future studies, ranging from ecology to algal biotechnology.

Greater Apathy Associated With Selective Serotonin Reuptake Inhibitor Use in Parkinson's Disease.

OBJECTIVE: Apathy, a motivational disorder, is common in Parkinson's disease (PD) and often misdiagnosed as depression. Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with increased apathy in adolescents and adults with depression. Based on observations that serotonin may downregulate dopaminergic systems, we examined the relationship between apathy and SSRI use in individuals with PD. METHODS: Medications, mood/motivation scales, and clinical data were collected from a convenience sample of 400 individuals with PD. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped by mechanism type. RESULTS: Of the 400 PD patients, 26% were on SSRIs. On standard mood/motivation scales, 38% of the sample exceeded clinical cut-offs for apathy and 28% for depression. Results of hierarchical regression analyses revealed that SSRIs were the only antidepressant that were significantly associated with higher apathy scores (ß = .1, P = .02). Less education (ß = -.1, P = .01) worse cognition (ß = -.1, P = .01), and greater depressive symptoms (ß = .5, P < .001) were also significant predictors of apathy. CONCLUSION: These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy when determining which antidepressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative antidepressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study.

Histological assessment of microtia cartilage, a potential source of autograft tissue in ear reconstruction.

Cartilage is a strong and flexible connective tissue that has many forms and functions in our body. While cartilage exhibits some forms of limited repair, for the most part, it is not particularly regenerative. Thus, in situations where patients require cartilage reconstruction, surgeons may use autografts to replace missing or damaged tissue. Cartilage tissues from different regions of the body exhibit histological differences and are in limited supply. Thus, it is important to characterize these differences to determine the most appropriate autograft source. In the case of microtia, a congenital deformity where the pinna is underdeveloped, reconstruction commonly utilizes cartilage sourced from a patient's own costal cartilage. This presents a potential morbidity risk. In this study, we evaluate the histological characteristics of microtia cartilage compared with normal auricular and costal cartilage obtained from human patients undergoing surgical resection. Histochemistry was used to evaluate cellularity, lipid content, and ECM content. Using a Bayesian statistical approach, we determined that while costal cartilage is the standard tissue donor, the microanatomy of microtia cartilage more closely reflects normal auricular cartilage than costal cartilage. Therefore, microtia cartilage may serve as an additional reservoir for cartilage during reconstruction.

Edge effects and social behavior in three platyrrhines.

Social behavior is a key adaptation for group-living primates. It is important to assess changes to social behavior in human-impacted landscape zones to better understand the impact of anthropogenic disturbance on primate species. We investigated social behavior rate and type in three species of platyrrhines across 100 m anthropogenic edge and interior zones of a fragmented forest in Costa Rica, La Suerte Biological Research Station (LSBRS). Following results from other sites, we predicted that spider monkeys (Ateles geoffroyi), capuchin monkeys (Cebus imitator) and howler monkeys (Alouatta palliata) would show lower rates and fewer types of social behavior in forest edge compared to interior. We collected 1341 h of instantaneous focal data from 2017 to 2023 across the three monkey species. We found mixed support for our predictions, with spider and capuchin monkeys modifying some but not all aspects of social behavior across forest zones at LSBRS. Spider monkeys had lower rates of social behavior and capuchin monkeys performed different types of social behaviors in forest edge compared to interior at LSBRS. In contrast, howler monkeys did not modify social behavior. Two out of three platyrrhine species altered their social behavior when in anthropogenic edges, indicating behavioral adjustment when in human-altered habitat areas at LSBRS.

Environmental DNA reveals temporal variation in mesophotic reefs of the Humboldt upwelling ecosystems of central Chile: Toward a baseline for biodiversity monitoring of unexplored marine habitats.

Temperate mesophotic reef ecosystems (TMREs) are among the least known marine habitats. Information on their diversity and ecology is geographically and temporally scarce, especially in highly productive large upwelling ecosystems. Lack of information remains an obstacle to understanding the importance of TMREs as habitats, biodiversity reservoirs and their connections with better-studied shallow reefs. Here, we use environmental DNA (eDNA) from water samples to characterize the community composition of TMREs on the central Chilean coast, generating the first baseline for monitoring the biodiversity of these habitats. We analyzed samples from two depths (30 and 60 m) over four seasons (spring, summer, autumn, and winter) and at two locations approximately 16 km apart. We used a panel of three metabarcodes, two that target all eukaryotes (18S rRNA and mitochondrial COI) and one specifically targeting fishes (16S rRNA). All panels combined encompassed eDNA assigned to 42 phyla, 90 classes, 237 orders, and 402 families. The highest family richness was found for the phyla Arthropoda, Bacillariophyta, and Chordata. Overall, family richness was similar between depths but decreased during summer, a pattern consistent at both locations. Our results indicate that the structure (composition) of the mesophotic communities varied predominantly with seasons. We analyzed further the better-resolved fish assemblage and compared eDNA with other visual methods at the same locations and depths. We recovered eDNA from 19 genera of fish, six of these have also been observed on towed underwater videos, while 13 were unique to eDNA. We discuss the potential drivers of seasonal differences in community composition and richness. Our results suggest that eDNA can provide valuable insights for monitoring TMRE communities but highlight the necessity of completing reference DNA databases available for this region.

Frontal-temporal regional differences in brain energy metabolism and mitochondrial function using 31P MRS in older adults.

Aging is a major risk for cognitive decline and transition to dementia. One well-known age-related change involves decreased brain efficiency and energy production, mediated in part by changes in mitochondrial function. Damaged or dysfunctional mitochondria have been implicated in the pathogenesis of age-related neurodegenerative conditions like Alzheimer's disease (AD). The aim of the current study was to investigate mitochondrial function over frontal and temporal regions in a sample of 70 cognitively normal older adults with subjective memory complaints and a first-degree family history of AD. We hypothesized cerebral mitochondrial function and energy metabolism would be greater in temporal as compared to frontal regions based on the high energy consumption in the temporal lobes (i.e., hippocampus). To test this hypothesis, we used phosphorous (31P) magnetic resonance spectroscopy (MRS) which is a non-invasive and powerful method for investigating in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. We used a single voxel method (left temporal and bilateral prefrontal) to achieve optimal sensitivity. Results of separate repeated measures analyses of variance showed 31P MRS ratios of static energy, energy reserve, energy consumption, energy demand, and phospholipid membrane metabolism were greater in the left temporal than bilateral prefrontal voxels. Our findings that all 31P MRS ratios were greater in temporal than bifrontal regions support our hypothesis. Future studies are needed to determine whether findings are related to cognition in older adults.

Perception of cognitive change by individuals with Parkinson's disease or essential tremor seeking deep brain stimulation: Utility of the cognitive change index.

OBJECTIVE: The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson's disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS). METHODS: 216 participants (N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms. RESULTS: PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was well educated (m = 15.01 ± 2.92), in their mid-60's (m = 67.72 ± 9.33), predominantly male (63%), and non-Hispanic White (93.6%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory (p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints. CONCLUSION: Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.

The Relationship Between Autonomic Dysfunction and Mood Symptoms in De Novo Parkinson's Disease Patients Over Time.

BACKGROUND: Autonomic dysfunction is prevalent in Parkinson's disease (PD) and can worsen quality of life. We examined: (a) whether specific autonomic symptoms were more strongly associated with anxiety or depression in PD and (b) whether overall autonomic dysfunction predicted mood trajectories over a 5-year period. METHODS: Newly diagnosed individuals with PD (N = 414) from the Parkinson's Progression Markers Initiative completed self-report measures of depression, anxiety, and autonomic symptoms annually. Cross-sectional linear regressions examined relationships between specific autonomic subdomains (gastrointestinal, cardiovascular, thermoregulatory, etc.) and mood. Multilevel modeling examined longitudinal relationships with total autonomic load. RESULTS: Gastrointestinal symptoms were associated with both higher anxiety (b = 1.04, 95% CI [.55, 1.53], P < .001) and depression (b = .24, 95% CI [.11, .37], P = .012), as were thermoregulatory symptoms (anxiety: b = 1.06, 95% CI [.46, 1.65], P = .004; depression: b = .25, 95% CI [.09, .42], P = .013), while cardiovascular (b = .36, 95% CI [.10, .62], P = .012) and urinary symptoms (b = .10, 95% CI [.01, .20], P = .037) were associated only with depression. Longitudinally, higher total autonomic load was associated with increases in both depression (b = .01, 95% CI [.00, .02], P = .015) and anxiety (b = .04, 95% CI [.01, .06], P < .001) over time, as well as occasion-to-occasion fluctuations (depression: b = .08, 95% CI [.05, .10], P < .001; anxiety: b = .24, 95% CI [.15, .32], P < .001). CONCLUSION: Findings suggest autonomic dysfunction, particularly gastrointestinal and thermoregulatory symptoms, may be an indicator for elevated anxiety/depression and a potential treatment target early on in PD.

The role of cytochrome P450 3A4-mediated metabolism in sorafenib and lapatinib hepatotoxicity.

Tyrosine kinase inhibitors (TKIs) are increasingly popular drugs used to treat more than a dozen different diseases, including some forms of cancer. Despite having fewer adverse effects than traditional chemotherapies, they are not without risks. Liver injury is a particular concern. Of the FDA-approved TKIs, approximately 40% cause hepatotoxicity. However, little is known about the underlying pathophysiology. The leading hypothesis is that TKIs are converted by cytochrome P450 3A4 (CYP3A4) to reactive metabolites that damage proteins. Indeed, there is strong evidence for this bioactivation of TKIs in in vitro reactions. However, the actual toxic effects are underexplored. Here, we measured the cytotoxicity of several TKIs in primary mouse hepatocytes, HepaRG cells, and HepG2 cells with and without CYP3A4 modulation. To our surprise, the data indicate that CYP3A4 increases resistance to sorafenib and lapatinib hepatotoxicity. The results have implications for the mechanism of toxicity of these drugs in patients and underline the importance of selecting an appropriate experimental model.

Expansion of marine pollution along the coast: Negative effects on kelps and contamination transference to benthic herbivores?

Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants that frequently co-occur in coastal environments. These contaminants can have negative impacts on the health and stability of marine and coastal ecosystems, affecting both the organisms themselves and the humans who consume them. A coastal industrial park in central Chile, housing a coal thermal power plant and other industrial activities, contributes to such pollution of coastal waters; however, neither the spatial alongshore distribution of heavy metals and PAHs, nor an assessment of their ecological effects on the biota have been systematically documented to date. In this paper, we present evidence regarding the direct negative effect of contamination by heavy metals and PAHs on the early life stages of kelps-being extremely harmful to their population persistence near highly polluted sites-as well as the indirect effects of their transference through the food web to higher trophic levels, leading to negative consequences for the feeding intake, growth, fertility, and larval development of marine herbivores that consume the contaminated seaweed. Likewise, the dispersion of contaminants by ocean currents can exacerbate the effects of pollution, having an adverse influence on marine ecosystem health even at sites far from the pollution source. Therefore, it is necessary to investigate the distribution patterns and extent of pollution along the coast to understand the impact of heavy metals and PAHs pollution on seaweed populations and the food web. It is considered critical for the development of effective environmental policies and regulations to protect these ecosystems and the people who depend on them.

Frontal adenosine triphosphate markers from 31P MRS are associated with cognitive performance in healthy older adults: preliminary findings.

Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (31P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using 31P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of in vivo mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.

Early rapid eye movement sleep behavior disorder predicts incident cognitive impairment in Parkinson's disease across ages.

This study demonstrated possible rapid eye movement sleep behavior disorder (RBD)'s relationship to longitudinal, incident cognitive impairment in the Parkinson's Progression Markers Initiative (PPMI) database. Age did not moderate this relationship, suggesting that RBD serves as a cognitive risk factor across individuals of all ages with recently diagnosed Parkinson's disease.

Spatio-temporal patterns of the crustacean demersal fishery discard from the south Humboldt Current System, based on scientific observer program (2014-2019).

This study summarises six years of spatio-temporal patterns of the discarded demersal community fauna recorded by onboard scientific observer program for both artisanal and industrial crustacean fisheries between 2014 and 2019, from mesophotic to aphotic depths (96 to 650 m) along the southern Humboldt Current System (28-38°S). In this period, one cold and two warm climatic events were observed during the austral summer 2014, 2015-2016 (ENSO Godzilla), and 2016-2017 (coastal ENSO), respectively. Satellite information showed that Chlorophyll-a concentration varied seasonally and latitudinally, associated with upwelling centres, while equatorial wind stress decreased southward of 36°S. Discards were composed of 108 species, dominated by finfish and molluscs. The Chilean hake Merluccius gayi was dominant and ubiquitous (occurrence, 95% of 9104 hauls), being the most vulnerable species of the bycatch. Three assemblages were identified: assemblage 1 (~200 m deep), dominated by flounders Hippoglossina macrops and lemon crabs Platymera gaudichaudii, assemblage 2 (~260 m deep), dominated by squat lobsters Pleuroncodes monodon and Cervimunida johni and assemblage 3 (~320 m depth), dominated by grenadiers Coelorinchus aconcagua and cardinalfish Epigonus crassicaudus. These assemblages were segregated by depth, and varied by year, and geographic zone. The latter represented changes in the width of the continental shelf, increasing southward of 36°S. Alpha-diversity indexes (richness, Shannon, Simpson, and Pielou) also varied with depth and latitude, with higher diversity in deeper continental waters (>300 m), between 2018-2019. Finally, at a spatial scale of tens of kilometres, and a monthly basis, interannual variations of biodiversity occurred in the demersal community. Surface sea temperature, chlorophyll-a, or wind stress did not correlate with discarded demersal fauna diversity of the crustacean fishery operating along central Chile.

Effect of Sirt3 on hippocampal MnSOD activity, mitochondrial function, physiology, and cognition in an aged murine model.

The NAD(+)-dependent deacetylase SIRT3 is a proven mitochondrial metabolic stress sensor. It has been linked to the regulation of the mitochondrial acetylome and activation of several metabolic enzymes (e.g., manganese superoxide dismutase [MnSOD]) to protect mitochondrial function and redox homeostasis, which are vital for survival, excitability, and synaptic signaling of neurons mediating short- and long-term memory formation as well as retention. Eighteen-month-old male and female wild-type (WT) and Sirt3-/- mice were behaviorally tested for hippocampus-dependent cognitive performance in a Morris water maze paradigm. Cognitive impairment was displayed during the probe trial by female and male Sirt3-/- mice but not WT mice. Upon sacrifice, brains were fixed, and morphological assessments were conducted on hippocampal tissues. Both female and male Sirt3-/- mice demonstrated impaired spatial memory retention implying that SIRT3 plays a role in long-term memory function. Golgi-staining studies revealed decreased dendritic arborization and dendritic length in the hippocampi of male Sirt3-/- compared to WT animals. Sirt3 deletion significantly increased NR1, NR2A, and NR2B expression in the hippocampus of female mice only. Enzymatic activity of MnSOD, a major mitochondrial deacetylation target of SIRT3, was significantly decreased in both female and male Sirt3-/- mice. Similarly, both female and male Sirt3-/- mice demonstrated a significant decrease in their respiratory control ratio during Complex I-driven respiration, which was apparent only in female Sirt3-/- mice during Complex II-driven respiration.

Evaluation of 1,2-diacyl-3-acetyl triacylglycerol production in Yarrowia lipolytica.

Plants produce many high-value oleochemical molecules. While oil-crop agriculture is performed at industrial scales, suitable land is not available to meet global oleochemical demand. Worse, establishing new oil-crop farms often comes with the environmental cost of tropical deforestation. The field of metabolic engineering offers tools to transplant oleochemical metabolism into tractable hosts while simultaneously providing access to molecules produced by non-agricultural plants. Here, we evaluate strategies for rewiring metabolism in the oleaginous yeast Yarrowia lipolytica to synthesize a foreign lipid, 3-acetyl-1,2-diacyl-sn-glycerol (acTAG). Oils made up of acTAG have a reduced viscosity and melting point relative to traditional triacylglycerol oils making them attractive as low-grade diesels, lubricants, and emulsifiers. This manuscript describes a metabolic engineering study that established acTAG production at g/L scale, exploration of the impact of lipid bodies on acTAG titer, and a techno-economic analysis that establishes the performance benchmarks required for microbial acTAG production to be economically feasible.

What does the Dementia Rating Scale-2 measure? The relationship of neuropsychological measures to DRS-2 total and subscale scores in non-demented individuals with Parkinson's disease.

OBJECTIVE: The Dementia Rating Scale-2 (DRS-2) is recommended for assessing global cognition in Parkinson's disease (PD) by the Movement Disorder Society. However, empirical evidence is limited regarding the degree to which the DRS-2 corresponds to traditional neurocognitive domains (i.e., construct validity) in PD. Thus, this study aims to determine the construct validity of the DRS-2 in a non-demented sample of PD patients. METHOD: Patients with PD (n = 359; mean age = 64.50 ± 8.53, education = 14.97 ± 2.73, disease duration = 8.48 ± 4.87, UPDRS Part III motor scale scores = 25.23 ± 10.17) completed the DRS-2 as part of a comprehensive neuropsychological assessment consisting of attention/working memory, executive function, language, delayed recall, and visuoperceptual-spatial skills.Bootstrapped bias-corrected Spearman rho's correlations andhierarchical linear regressions were performed to examine construct validity of DRS-2 total and subscale scores. RESULTS: Speeded measures of set-shifting, rapid word generation to letter and semantic cues, and simple visuoperceptual skills largely accounted for variance in DRS-2 total scores. Most DRS-2 subscale scores showed weak relationships with theoretically related neuropsychological measures. CONCLUSIONS: DRS-2 total scores reflect impairment across a range of cognitive domains (i.e., executive, language, and visuoperception), while DRS-2 subscale scores have limited construct validity. Together, the DRS-2 does not appear to have utility beyond screening for global cognition in PD.

Unpacking the NIH Toolbox Emotion Battery in Persons With Parkinson's disease.

OBJECTIVE: Examine the relationship between the National Institutes of Health Toolbox Emotion Battery (Emotion Toolbox) and traditional measures in Parkinson's disease (PD). METHOD: Persons with PD (n = 30) and cognitively healthy older adults (OA; n = 40) completed the Emotion Toolbox consisting of Well-Being, Negative Affect, and Social Satisfaction scores along with traditional measures of depression (Beck Depression Inventory-II [BDI-II]), anxiety (State-Trait Anxiety Inventory [STAI]), and apathy (Apathy Scale [AS]); total raw scores). RESULTS: Separate bootstrapped analyses of covariance indicated that the PD group scored higher on BDI-II and STAI-State compared to OA (ps < .01); groups did not differ on Emotion Toolbox. In the PD group, bootstrapped partial correlations indicated that Negative Affect was positively related to BDI-II and STAI (ps ≤ .001). Social Satisfaction was negatively related to BDI-II and STAI-Trait (.05 < ps < .004). Psychological Well-Being was negatively related to BDI-II, AS, and STAI (p < .004). No relationships emerged in OA. In the PD group, separate binary logistic regressions showed that traditional measures (BDI-II, AS, and STAI-Trait) correctly classified 79.6% those with formal psychiatric diagnoses (presence vs. absence; p < .011), whereas Emotion Toolbox measures correctly classified 73.3% (p < .019). CONCLUSIONS: The Emotion Toolbox showed moderate-strong correlations with traditional measures in persons with PD. Even so, it did not capture the group differences between PD and OA and had a somewhat lower classification accuracy rate for persons with PD who had a formal psychiatric diagnosis than traditional measures. Together, findings question the utility of the Emotion Toolbox as a stand-alone emotion screener in PD.

Combinatorial library design for improving isobutanol production in Saccharomyces cerevisiae.

Saccharomyces cerevisiae is the dominant fermentative producer of ethanol in industry and a preferred host for production of other biofuels. That said, rewiring the metabolism of S. cerevisiae to produce other fermentation products, such as isobutanol, remains an academic challenge. Many studies report aerobic production of isobutanol, but ethanol remains a substantial by-product under these conditions due to the Crabtree effect. These studies indicate that the native isobutanol pathway is incapable of carrying sufficient flux to displace ethanol. In this report, we screened a combinatorial library of pathway enzymes to identify an isobutanol pathway cassette capable of supporting the growth of a non-ethanol producing S. cerevisiae. We began by identifying a diverse set of isobutanol pathway enzyme homologs and combined each open reading frame with varied-strength promoters in a combinatorial, pooled fashion. We applied a growth-coupled screen where a functional isobutanol pathway restored NAD+ regeneration during glucose catabolism that is otherwise repressed via the Crabtree effect. Using this screen, we isolated a cassette consisting of a mosaic of bacterial and cytosol-localized fungal enzymes that conferred under aerobic conditions the ability to produce 364 mg/L isobutanol (8.8% of the theoretical maximum yield). We next shifted the cofactor usage of the isolated ketol-acid reductoisomerase enzyme in the cassette from NADPH to NADH-preferring to improve redox balance. The approach used herein isolated isobutanol producing strains that approach the best in the literature without producing substantial ethanol titers. Still, the best isolated cassette was insufficient to support anaerobic growth in the absence of ethanol fermentation - indicating the presence of further fundamental gaps in our understanding of yeast fermentation.

A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog.

Building and maintaining skeletal tissue requires the activity of skeletal stem and progenitor cells (SSPCs). Following injury, local pools of these SSPCs become active and coordinate to build new cartilage and bone tissues. While recent studies have identified specific markers for these SSPCs, how they become activated in different injury contexts is not well-understood. Here, using a model of large-scale rib bone regeneration in mice, we demonstrate that the growth factor, Sonic Hedgehog (SHH), is an early and essential driver of large-scale bone healing. Shh expression is broadly upregulated in the first few days following rib bone resection, and conditional knockout of Shh at early but not late post-injury stages severely inhibits cartilage callus formation and later bone regeneration. Whereas Smoothened (Smo), a key transmembrane component of the Hh pathway, is required in Sox9+ lineage cells for rib regeneration, we find that Shh is required in a Prrx1-expressing, Sox9-negative mesenchymal population. Intriguingly, upregulation of Shh expression and requirements for Shh and Smo may be unique to large-scale injuries, as they are dispensable for both complete rib and femur fracture repair. In addition, single-cell RNA sequencing of callus tissue from animals with deficient Hedgehog signaling reveals a depletion of Cxcl12-expressing cells, which may indicate failed recruitment of Cxcl12-expressing SSPCs during the regenerative response. These results reveal a mechanism by which Shh expression in the local injury environment unleashes large-scale regenerative abilities in the murine rib.