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Abstract Borderline personality disorder (BPD) is characterized by patterns of unstable affect, unstable interpersonal relationships, and chronic suicidal tendencies. Research on the genetics, epigenetics, and brain function of BPD is lacking. MicroRNA-124-3p (miR-124-3p) was recently identified in a Genome-Wide Association Study as likely associated with BPD. Here, we identified the anatomical brain expression of genes likely modulated by miR-124-3p and compared morphometry in those brain regions in BPD inpatients vs. controls matched for psychiatric comorbidities. We isolated lists of targets likely modulated by miR-124-3p from TargetScan (v 8.0) by their preferentially conserved targeting (Aggregate PCT > 0.99, see Supplementary Table 1). We applied Process Genes List (PGL) to identify regions of interest associated with the co-expression of miR-124-3p target genes. We compared the gray matter volume of the top region of interest co-expressing those genes between BPD inpatients (n = 111, 46% female) and psychiatric controls (n = 111, 54% female) at The Menninger Clinic in Houston, Texas. We then correlated personality measures, suicidal ideation intensity, and recovery from suicidal ideation with volumetrics. Gene targets of miR-124-3p were significantly co-expressed in the left Globus Pallidus (GP), which was smaller in BPD than in psychiatric controls. Smaller GP volume was negatively correlated with agreeableness and with recovery from suicidal ideation post-treatment. In BPD, GP volume may be reduced through miR-124-3p regulation and suppression of its target genes. Importantly, we identified that a reduction of the GP in BPD could serve as a potential biomarker for recovery from suicidal ideation.

Background Brain imaging and genetics are fields acquiring data at increasing speed, but more information does not always result in a better understanding of the underlying biology. We developed the ProcessGeneLists (PGL) approach to use genetics and mRNA gene expression data to generate regions of interest for imaging studies. Methods We applied PGL to past suicide attempt (ATT): We averaged the mRNA expression levels of genes (n = 130) possibly associated with ATT (p ≤ 10 −3 in a published genome-wide association study, GWAS) in each brain region studied in the Human Allen Brain Atlas (6 ex-vivo brains, 158 to 946 regions/brain have mRNA expression data) and compared that to the averaged mRNA expression levels of all other genes in each region in each brain in the atlas. Results PGL revealed 8 regions where “attempt-related genes” were differentially expressed (Wilcoxon test with Bonferroni correction 8.88 −11 =

Anti-drug vaccines previously failed clinical trials because they did not provide a sufficient titer or duration of antibodies (AB), but new adjuvants enhance both AB titers and efficacy duration. This clinical trial assessed AB titers after a single booster of commercial tetanus-diphtheria (Td) vaccine in 40 males randomized as 15 to Td alone and 25 to Td combined with the TLR5 adjuvant, Entolimod (Ent). Ent significantly increased ABs against diphtheria (DPT) (0.46 vs. 0.29 IU/mL increase; n = 40, p < 0.05), but against tetanus (TT) only if baseline TT AB was below 3 IU/mL (3.1 vs. 2.1 IU/mL; n = 20; p < 0.05). These 20 participants also showed a two-fold increase in anti-TT AB titer more often when given Ent than non-Ent (33% vs. 82%) (p < 0.03). Anti-Ent AB was low and appeared unlikely to reduce Ent efficacy after repeated Ent administration. Medical safety was excellent, and a TLR5 missense polymorphism reduced anti-DPT AB production, but Ent increased anti-DPT AB titers to levels induced in subjects with genetically “normal” TRL5 functioning. Further clinical testing of TLR5 adjuvants like Ent seems warranted for anti-drug vaccines.

The contact hypothesis has dominated work on prejudice reduction and is often described as one of the most successful theories within social psychology. The hypothesis has nevertheless been criticized for not being applicable in real life situations due to unobtainable conditions for direct contact. Several indirect contact suggestions have been developed to solve this “application challenge.” Here, we suggest a hybrid strategy of both direct and indirect contact. Based on the second-person method developed in social psychology and cognition, we suggest working with an engagement strategy as a hybrid hypothesis. We expand on this suggestion through an engagement-based intervention, where we implement the strategy in a theater performance and investigate the effects on prejudicial attitudes toward people with physical disabilities. Based on the results we reformulate our initial engagement strategy into the Enact (Engagement, Nuancing, and Attitude formation) hypothesis. To deal with the application challenge, this hybrid hypothesis posits two necessary conditions for prejudice reduction. Interventions should: (1) work with engagement to reduce prejudice, and (2) focus on the second-order level of attitudes formation. Here the aim of the prejudice reduction is not attitude correction, but instead the nuancing of attitudes.

Precipitation varies greatly from east to west across the US Great Plains. Farmers would have a better means of understanding the applicability of cropping systems research done in one part of the Great Plains to their specific location if they were aware of the rate of change of precipitation with east–west direction at their latitude. The objective of this analysis was to determine if a consistent, predictive relationship exists between the east–west precipitation gradient and latitude in the Great Plains. The east–west precipitation gradient was determined for 15 transects from Texas to North Dakota. The precipitation gradient changed little from 31° N lat. to 38° N lat. and then increased systematically for latitudes further north. A quadratic polynomial relationship fit the data well ( = 0.967) and was used to create a simple spreadsheet decision support tool to help farmers understand how quickly precipitation changes with east–west direction at a given latitude.

Objective: Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Methods: Sixty-seven cocaine dependent patients were stabilized on methadone for two weeks and then randomized into disulfiram (250 mg/day, N = 32) and placebo groups (N =35) for 10 weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all ten weeks of the study (N = 56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. Results: The CT or TT MTHFR genotype group (N = 32) dropped from 73% to 52% on disulfiram (p = 0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N = 24) showed a reduced, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81-69% (p = 0.007). Conclusion: This study indicates that a patient’s MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence.

The use of automated methods to estimate fractional vegetation cover (FVC) from digital photographs has increased in recent years given its potential to produce accurate, fast and inexpensive FVC measurements. Wide acceptance has been delayed because of the limitations in accuracy, speed, automation and generalization of these methods. This work introduces a novel technique, the Automated Canopy Estimator (ACE) that overcomes many of these challenges to produce accurate estimates of fractional vegetation cover using an unsupervised segmentation process. ACE is shown to outperform nine other segmentation algorithms, consisting of both threshold-based and machine learning approaches, in the segmentation of photographs of four different crops (oat, corn, rapeseed and flax) with an overall accuracy of 89.6%. ACE is similarly accurate (88.7%) when applied to remotely sensed corn, producing FVC estimates that are strongly correlated with ground truth values.

By applying metabolic engineering tools and strategies to engineer synthetic enzyme pathways, the number and diversity of commodity and specialty chemicals that can be derived directly from renewable feedstocks is rapidly and continually expanding. This of course includes a number of monomer building-block chemicals that can be used to produce replacements to many conventional plastic materials. This review aims to highlight numerous recent and important advancements in the microbial production of these so-called ‘biomonomers’. Relative to naturally-occurring renewable bioplastics, biomonomers offer several important advantages, including improved control over the final polymer structure and purity, the ability to synthesize non-natural copolymers, and allowing products to be excreted from cells which ultimately streamlines downstream recovery and purification. To highlight these features, a handful of biomonomers have been selected as illustrative examples of recent works, including polyamide monomers, styrenic vinyls, hydroxyacids, and diols. Where appropriate, examples of their industrial penetration to date and end-product uses are also highlighted. Novel biomonomers such as these are ultimately paving the way towards new classes of renewable bioplastics that possess a broader diversity of properties than ever before possible.

Background: Human cocaine abuse is associated with alterations in white matter integrity revealed upon brain imaging, an observation that is recapitulated in an animal model of continuous cocaine exposure. The mechanism through which cocaine may affect white matter is unknown and the present study tested the hypothesis that cocaine self-administration results in changes in DNA methylation that could result in altered expression of several myelin genes that could contribute to the effects of cocaine on white matter integrity.Methods: In the present study, we examined the impact of forced abstinence from cocaine self-administration on chromatin-associated changes in white matter. To this end, rats were trained to self-administer cocaine (0.75 mg/kg/0.1 ml infusion) for 14 days followed by forced abstinence for 1 day (N = 6) or 30 days (N = 6) before sacrifice. Drug-free, sham surgery controls (n = 7) were paired with the experimental groups. Global DNA methylation and DNA methylation at specific CpG sites in the promoter regions of myelin basic protein (Mbp), proteolipid protein-1 (Plp1), and SRY-related HMG-box-10 (Sox10) genes were analyzed in DNA extracted from corpus callosum.Results: Significant differences in the overall methylation patterns of the Sox10 promoter region were observed in the corpus callosum of rats at 30 days of forced abstinence from cocaine self-administration relative to sham controls; the -189, -142, -93 and -62 CpG sites were significantly hypomethylated point-wise at this time point. After correction for multiple comparisons, no differences in global methylation or the methylation patterns of Mbp or Plp1 were found.Conclusions: Forced abstinence from cocaine self-administration was associated with differences in DNA methylation at specific CpG sites in the promoter region of the Sox10 gene in corpus callosum. These changes may be related to reductions in normal age related changes in DNA methylation and could be a factor in white mat

Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users.Seventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05-16) and in the other cocaine (20 mg) or money.Participants chose cocaine more than saline under both disulfiram and placebo conditions (p

The mu-opioid receptor is encoded by the Oprm1 gene and contributes to mother-infant behaviors. Rodent dams lick male pups more than female pups in the anogenital region. This behavior is linked to stress responsivity in the offspring that may be mediated by epigenetic changes. We hypothesized that maternal behavior may affect DNA methylation levels of the Oprm1 gene and show sex differences. To further explore sex differences in mother-pup behaviors and DNA methylation levels, we altered the litter gender composition (LGC) of rats. Litters were culled to 8 all male, all female, or 4 male/4 female pups on postnatal (PN) day 1. On PN4, 7, and 10, a dam was placed in a test cage with a pup for a 10-min period. Latency to pup contact was determined as were times spent licking the anogenital and other body regions of the pup. Frequencies of other behaviors were tabulated. On PN35, samples from various brain regions were obtained. DNA methylation at specific CpG sites in the Oprm1 promoter region were measured by direct sequencing of bisulfite treated DNA. LGC and sex interacted with day for latency to pup contact. Latencies were longest on PN4 for single-sex males and on PN10 for single-sex females. Dams licked male pups more than female pups in both the anogenital and other body areas. Sex differences were seen in other behaviors. LGC altered DNA methylation at specific CpG’s of Oprm1 in hippocampus with higher levels in single-sex rats. In nucleus accumbens, single-sex males showed hypermethylation levels, a trend seen in caudate-putamen. Results confirm and extend sex differences in maternal care with modest LGC effects. That both LGC and sex have enduring effects on DNA methylation of the Oprm1 gene in brain regions associated with addiction, stress regulation, motivation, and cognition may suggest one factor that contributes to gender differences in these behaviors.

Abstract Since 2007, unprecedented marine heatwave events are occurring over the Arctic Ocean. Here we identify the fraction of the likelihood of Arctic marine heatwaves magnitude that is attributable to greenhouse gas forcing. Results reveal that Arctic marine heatwaves are primarily triggered by an abrupt sea-ice retreat, which coincides with the maximum downward radiative fluxes. Up to 82% of the sea surface temperature variability over the shallow Arctic marginal seas, where marine heatwaves are prone to occur, can be explained by net accumulation of seasonal surface heat flux in the ocean. Event attribution analysis demonstrates that the 103-day long 2020 event – the most intense (4 ∘C) recorded so far in the Arctic – would be exceptionally unlikely in the absence of greenhouse gas forcing in terms of both intensity and duration. Our further results imply that if greenhouse gas emissions continue to rise, along with the expansion of first-year ice extent, moderate marine heatwaves in the Arctic will very likely persistently reoccur.

In this paper, the problem of estimating a scalar field (e.g., the spatial distribution of contaminants in an area) using a sensor network is considered. The sensors are assumed to have quantized measurements. We consider distributed estimation algorithms where each sensor forms its own estimate of the field, with sensors able to share information locally with its neighbours. Two schemes are proposed, called, respectively, measurement diffusion and estimate diffusion. In the measurement diffusion scheme, each sensor broadcasts to its neighbours the latest received measurements of every sensor in the network, while in the estimate diffusion scheme, each sensor will broadcast local estimates and Hessians to its neighbours. Information received from its neighbours will then be iteratively combined at each sensor to form the field estimates. Time-varying scalar fields can also be estimated using both the measurement diffusion and estimate diffusion schemes. Numerical studies illustrate the performance of the proposed algorithms, in particular demonstrating steady state performance close to that of centralized estimation.

A multi-year marine heat wave in the northeast Pacific warming pool, as the one that occurred from 2019 to 2021, would almost certainly not have occurred in the absence of anthropogenic global warming, according to a climate model-based attribution study.

Architectural development in Colombia has been concentrated in large cities and has been characterized by the implementation of methodologies adapted to consumption and that generate a disruption of the environment and depletion of resources. Sustainable architecture seeks to mitigate the environmental damage of housing through elements such as bioclimatic and the use of methodologies for the proper management of resources. Thus, biomimicry, an area that studies structures, systems and processes present in nature for the resolution of human problems, is a source of inspiration for conscious and transformative architecture. The main objective was a proposal for the design of a rural housing bio-inspired in the paipan Frailejón (Espeletia paipana), which would mitigate the environmental impact of its construction and operation. The designed housing has a modular distribution and a water condensation system inspired in the rosette and pubescent conformation of the Frailejón, respectively. Likewise, it has methodologies of transformation and use of resources to diminish the deterioration of the environment and the energetic demand. In conclusion, it establishes the possibility of supporting responsible rural development based on biomimetic design and the territory as a source of inspiration.

Although biological upgrading of lignocellulosic sugars represents a promising and sustainable route to bioplastics, diverse and variable feedstock compositions (e.g., glucose from the cellulose fraction and xylose from the hemicellulose fraction) present several complex challenges. Specifically, sugar mixtures are often incompletely metabolized due to carbon catabolite repression while composition variability further complicates the optimization of co-utilization rates. Benefiting from several unique features including division of labor, increased metabolic diversity, and modularity, synthetic microbial communities represent a promising platform with the potential to address persistent bioconversion challenges. In this work, two unique and catabolically orthogonal Escherichia coli co-cultures systems were developed and used to enhance the production of D-lactate and succinate (two bioplastic monomers) from glucose–xylose mixtures (100 g L–1 total sugars, 2:1 by mass). In both cases, glucose specialist strains were engineered by deleting xylR (encoding the xylose-specific transcriptional activator, XylR) to disable xylose catabolism, whereas xylose specialist strains were engineered by deleting several key components involved with glucose transport and phosphorylation systems (i.e., ptsI, ptsG, galP, glk) while also increasing xylose utilization by introducing specific xylR mutations. Optimization of initial population ratios between complementary sugar specialists proved a key design variable for each pair of strains. In both cases, ∼91% utilization of total sugars was achieved in mineral salt media by simple batch fermentation. High product titer (88 g L–1 D-lactate, 84 g L–1 succinate) and maximum productivity (2.5 g L–1 h–1 D-lactate, 1.3 g L–1 h–1 succinate) and product yield (0.97 g g-total sugar–1 for D-lactate, 0.95 g g-total sugar–1 for succinate) were also achieved.

In the Pacific Ocean, off-equatorial Rossby waves (RWs), initiated by atmosphere-ocean interaction, modulate the inter-annual variability of the thermocline. In this study, we explore the resulting potential gain in predictability of central tropical Pacific primary production, which in this region strongly depends on the supply of macronutrients from below the thermocline. We use a decadal prediction system based on the Max Planck Institute Earth system model to demonstrate that for the time period 1998–2014 properly initialized RWs explain an increase in predictability of net primary productivity (NPP) in the off-equatorial central tropical Pacific. We show that, for up to 5 years in advance, predictability of NPP derived from the decadal prediction system is significantly larger than that derived from persistence alone, or an uninitialized historical simulation. The predicted signal can be explained by the following mechanism: off-equatorial RWs are initiated in the eastern Pacific and travel towards the central tropical Pacific on a time scale of 2–6 years. On their arrival the RWs modify the depths of both thermocline and nutricline, which is fundamental to the availability of nutrients in the euphotic layer. Local upwelling transports nutrients from below the nutricline into the euphotic zone, effectively transferring the RW signal to the near-surface ocean. While we show that skillful prediction of central off-equatorial tropical Pacific NPP is possible, we open the door for establishing predictive systems for food web and ecosystem services in that region.

Phenol is an important petrochemical that is conventionally used as a precursor for synthesizing an array of plastics and fine chemicals. As an emerging alternative to its traditional petrochemical production, multiple enzyme pathways have been engineered to date to enable its renewable biosynthesis from biomass feedstocks, each incorporating unique enzyme chemistries and intermediate molecules. Leveraging all three of the unique phenol biosynthesis pathways reported to date, a series of synthetic ‘metabolic funnels’ was engineered, each with the goal of maximizing net precursor assimilation and flux towards phenol via the parallel co-expression of multiple distinct pathways within the same Escherichia coli host. By constructing and evaluating all possible binary and tertiary pathway combinations, one ‘funnel’ was ultimately identified, which supported enhanced phenol production relative to all three individual pathways by 16 to 69%. Further host engineering to increase endogenous precursor availability then allowed for 26% greater phenol production, reaching a final titer of 554 ± 19 mg/L and 28.8 ± 0.34 mg/g yield on glucose. Lastly, using a diphasic culture including dibutyl phthalate for in situ phenol extraction, final titers were further increased to a maximum of 812 ± 145 mg/L at a yield of 40.6 ± 7.2 mg/g. The demonstrated ‘funneling’ pathway holds similar promise in support of phenol production by other, non-E. coli hosts, while this general approach can be readily extended towards a diversity of other value-added bioproducts of interest.

Benzyl alcohol is an aromatic hydrocarbon used as a solvent and an intermediate chemical in the pharmaceutical, cosmetics, and flavor/fragrance industries. The de novo biosynthesis of benzyl alcohol directly from renewable glucose was herein explored using a non-natural pathway engineered in Escherichia coli. Benzaldehyde was first produced from endogenous phenylpyruvate via three heterologous steps, including hydroxymandelate synthase (encoded by hmaS) from Amycolatopsis orientalis, followed by (S)-mandelate dehydrogenase (encoded by mdlB) and phenylglyoxylate decarboxylase (encoded by mdlC) from Pseudomonas putida ATCC 12633. The subsequent rapid and efficient reduction of benzaldehyde to benzyl alcohol occurred by the combined activity and native regulation of multiple endogenous alcohol dehydrogenases and/or aldo-keto reductases. Through systematic deletion of competing aromatic amino acid biosynthesis pathways to promote endogenous phenylpyruvate availability, final benzyl alcohol titers as high as 114±1 mg/L were realized, representing a yield of 7.6±0.1 mg/g on glucose and a ~5-fold improvement over initial strains. Keywords: Benzyl alcohol, Benzaldehyde, Aromatic chemicals

We found that 14.3% (15/105) of Amblyomma maculatum and 3.3% (10/299) of Dermacentor variabilis ticks collected at 3 high-use military training sites in west-central Kentucky and northern Tennessee, USA, were infected with Rickettsia parkeri and Rickettsia montanensis, respectively. These findings warrant regional increased public health awareness for rickettsial pathogens and disease.