Cysteine Residues Contribute to the Dimerization and Enzymatic Activity of Human Nuclear dUTP Nucleotidohydrolase (nDut).

dUTPase is an enzyme found in all organisms that have thymine as a constituent of DNA. Through evolution, humans have two major isoforms of dUTPase: a mitochondrial (mDut) and a nuclear (nDut) isoform. The nuclear isoform of dUTPase is a 164-amino-acids-long protein containing three cysteine residues. nDut\u27s starting methionine is post-translationally cleaved, leaving four unique amino acids on its amino-terminus including one cysteine residue (C3). These are not present in the mitochondrial isoform (mDut). Using mass spectrometry analyses of recombinant dUTPase constructs, we have discovered an intermolecular disulfide bridge between cysteine-3 of each nDut monomer. We have found that these two residues stabilize a dimer configuration that is unique to the nDut isoform. We have also uncovered an intramolecular disulfide linkage between cysteine residues C78 and C134, stabilizing the monomeric state of the protein. Of note, both disulfide linkages are essential for nDut\u27s enzymatic activity and dimeric formation can be augmented by the addition of the oxidizing agent, hydrogen peroxide to cells. Analyses of endogenous cellular dUTPase proteins confirm these differences between the two isoforms. We observed that mDut appears to be a mixture of monomer, dimer, and trimer conformations, as well as higher-order subunit interactions. In contrast, nDut appeared to exist only in monomeric and dimeric forms. Cysteine-based redox switches have recently emerged as a distinct class of post-translational modification. In light of this and our results, we propose that nDut possesses a redox switch whereby cysteine interactions regulate nDut\u27s dUTP-hydrolyzing activity

Testing perceivers’ accuracy and accuracy awareness when forming personality impressions from faces

People spontaneously judge others’ personality based on their facial appearance and these impressions guide many important decisions. Although the consequences of personality impressions are well documented, studies on the accuracy of personality impressions have yielded mixed results. Moreover, relatively little is known about people’s accuracy awareness (i.e., whether they are aware of their judgment accuracy). Even if accuracy is generally low, awareness of accuracy would allow people to rely on their impressions in the right situations. In two studies (one preregistered), we estimated perceivers’ accuracy and accuracy awareness when forming personality impressions based on facial photographs. Our studies have three crucial advantages as compared to previous studies (a) by incentivizing accuracy and accuracy awareness, (b) by relying on substantially larger samples of raters (nStudy 1 = 223, nStudy 2 = 423) and targets (kStudy 1 = 140, kStudy 2 = 1,260 unique pairs with 280 unique targets), and (c) by conducting Bayesian analyses to also quantify evidence for the null hypothesis. Our findings suggest that face-based personality impressions are not accurate, that perceivers lack insight into their (in)accuracy, and that most people overestimate their accuracy

High frequency environmental DNA metabarcoding provides rapid and effective monitoring of fish community dynamics

Long‐term monitoring is critical to measure the response of biodiversity patterns and processes to human‐mediated environmental pressures. This is particularly pertinent in freshwaters, where recent estimates indicated a third of all fish species are threatened with extinction, making ongoing biomonitoring essential for conservation management. High frequency annual monitoring is critical for identifying temporal changes in fish community composition; however, traditional survey methods are typically less practical over such timeframes. While environmental (e)DNA measurement represents a potentially powerful tool for monitoring temporal community dynamics, studies are lacking. To address this deficit, we generated a high frequency time‐series dataset of entire fish communities using eDNA metabarcoding, to directly assess the repeatability and sensitivity of this method for detecting annual population trends. We targeted two differing environments (freshwater vs. intertidal) within the Thames catchment, UK, where detailed historical records from traditional monitoring were available for comparison. To test how robust eDNA data is for inferring the known community, we applied a hierarchical, nested design encompassing short and longer‐term variation in eDNA data. Our analyses showed that irrespective of environment, eDNA metabarcoding represented known seasonal shifts in fish communities, where increased relative read abundance of eDNA coincided with known migratory and spawning events, including those of the critically endangered native species Anguilla anguilla (European eel). eDNA species detections across a single year included over 75% of species recorded in a ca. 30‐year historical dataset, highlighting the power of eDNA for species detection. Our findings provide greater insight into the utility of eDNA metabarcoding for recovering temporal trends in fish communities from dynamic freshwater systems and insight into the potential best sampling strategy for future eDNA surveys

The effectiveness of Payments for Ecosystem Services at delivering improvements in water quality: lessons for experiments at the landscape scale

Background Randomised Control Trials (RCTs) are used in impact evaluation in a range of fields. However, despite calls for their greater use in environmental management, their use to evaluate landscape scale interventions remains rare. Payments for Ecosystem Services (PES) incentivise land users to manage land to provide environmental benefits. We present the first RCT evaluation of a PES program aiming to improve water quality. Watershared is a program which incentivises landowners to avoid deforestation and exclude cattle from riparian forests. Using this unusual landscape-scale experiment we explore the efficacy of Watershared at improving water quality, and draw lessons for future RCT evaluations of landscape-scale environmental management interventions. Methods One hundred and twenty-nine communities in the Bolivian Andes were randomly allocated to treatment (offered Watershared agreements) or control (not offered agreements) following baseline data collection (including Escherichia coli contamination in most communities) in 2010. We collected end-line data in 2015. Using our end-line data, we explored the extent to which variables associated with the intervention (e.g. cattle exclusion, absence of faeces) predict water quality locally. We then investigated the efficacy of the intervention at improving water quality at the landscape scale using the RCT. This analysis was done in two ways; for the subset of communities for which we have both baseline and end-line data from identical locations we used difference-in-differences (matching on baseline water quality), for all sites we compared control and treatment at end-line controlling for selected predictors of water quality. Results The presence of cattle faeces in water adversely affected water quality suggesting excluding cattle has a positive impact on water quality locally. However, both the matched difference-in-differences analysis and the comparison between treatment and control communities at end-line suggested Watershared was not effective at reducing E. coli contamination at the landscape scale. Uptake of Watershared agreements was very low and the most important land from a water quality perspective (land around water intakes) was seldom enrolled. Discussion Although excluding cattle may have a positive local impact on water quality, higher uptake and better targeting would be required to achieve a significant impact on the quality of water consumed in the communities. Although RCTs potentially have an important role to play in building the evidence base for approaches such as PES, they are far from straightforward to implement. In this case, the randomised trial was not central to concluding that Watershared had not produced a landscape scale impact. We suggest that this RCT provides valuable lessons for future use of randomised experiments to evaluate landscape-scale environmental management interventions

The Small Magellanic Cloud Investigation of Dust and Gas Evolution (SMIDGE): The Dust Extinction Curve from Red Clump Stars

We use Hubble Space Telescope (HST) observations of red clump stars taken as part of the Small Magellanic Cloud Investigation of Dust and Gas Evolution (SMIDGE) program to measure the average dust extinction curve in a ~ 200 pc x 100 pc region in the southwest bar of the Small Magellanic Cloud (SMC). The rich information provided by our 8-band ultra-violet through near-infrared photometry allows us to model the color-magnitude diagram of the red clump accounting for the extinction curve shape, a log-normal distribution of $A_{V}$, and the depth of the stellar distribution along the line of sight. We measure an extinction curve with $R_{475} = A_{475}/(A_{475}-A_{814})$ = 2.65 $\pm$ 0.11. This measurement is significantly larger than the equivalent values of published Milky Way $R_{V}$ = 3.1 ($R_{475} = 1.83$) and SMC Bar $R_{V}$ = 2.74 ($R_{475} = 1.86$) extinction curves. Similar extinction curve offsets in the Large Magellanic Cloud (LMC) have been interpreted as the effect of large dust grains. We demonstrate that the line-of-sight depth of the SMC (and LMC) introduces an apparent "gray" contribution to the extinction curve inferred from the morphology of the red clump. We show that no gray dust component is needed to explain extinction curve measurements when a full-width half-max depth of 10 $\pm$ 2 kpc in the stellar distribution of the SMC (5 $\pm$ 1 kpc for the LMC) is considered, which agrees with recent studies of Magellanic Cloud stellar structure. The results of our work demonstrate the power of broad-band HST imaging for simultaneously constraining dust and galactic structure outside the Milky Way.Comment: 16 pages, 12 figures, 5 tables. Accepted for publication in Ap

Utilization of the Social Determinants of Mental Health Framework with Older Adults for Assessment, Case Conceptualization, and Treatment Planning

This conceptual paper will aid counselors and mental health professionals in obtaining insight to utilizing a Social Determinants of Mental Health Framework with older adult clients. Further, the article incorporates the Multicultural and Social Justice Counseling Competencies to further contextualize the therapeutic alliance. The authors utilize the Social Determinants of Mental Health Framework to frame counseling assessment, case conceptualization, and treatment planning to improve the mental health outcomes of older adults. The article utilizes a specific case example to assess, conceptualize, and plan treatment for an older adult client contextualized in their environment

Transcriptional Enhancers in the Regulation of T Cell Differentiation

The changes in phenotype and function that characterise the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression. In turn, these changes are choreographed by the interplay between transcription factors and epigenetic regulators that act to restructure the genome, ultimately ensuring lineage-appropriate gene expression. Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers. We discuss the central role of transcriptional enhancers in regulating T cell differentiation, both in health and disease

Clinically significant personality traits in individuals at high risk of developing psychosis

It is still unclear to what extent personality may influence the development of psychosis. We aimed to explore significant personality traits in individuals at high-risk (HR) for psychosis. Personalities of forty HR individuals and a matched sample of 40 HVs were evaluated with the Millon Multiaxial Inventory (MCMI-III). They were also assessed with the Positive and Negative Symptoms Scale (PANSS), Beck Depression and Anxiety Inventories (BDI-II and BAI), Global Assessment of Functioning (GAF) and Mini-International Neuropsychiatric Interview (MINI 6.0.0). Fisher's exact test was employed to compare frequency of traits. Mann-Whitney U test and logistic regression were used to establish relationships between traits and symptoms, and the effect of age, sex and symptoms on such traits. Most HR individuals (97.5%) had at least one significant trait; 75% had personality disorders, mainly depressive, borderline or schizotypal. Only histrionic and narcissistic traits were more prevalent in HVs. Negative symptoms were related to schizoid and paranoid traits. Depression was more severe with borderline traits. Most HR individuals (67.6%) had more than one DSM-IV Axis I diagnosis, mainly depressive/anxiety disorders. Transition rate was low (5%). Certain personality profiles may not be markers for conversions to psychosis but contribute to high morbidity in HR individuals