Open Regions Research Articles

Variability of heat stress using the UrbClim climate model in the city of Seville (Spain): mitigation proposal

Climate change is creating an increase in temperatures, which is harming the quality of life of people all over the world, particularly those with minimal financial resources. While 30% of the world’s population is now vulnerable to extreme heat, estimates show that ratio will rise to 74% in the next 20 years, according to forecasts. Using the UrbClim climate model, this study examines the space-time variability of the heat stress index (HI) in different local climate zones (LCZs), as well as how heat wave conditions might affect this index based on land use and land cover. To that end, Seville, in Southern Spain, was investigated during the summer of 2017, when it had four heat waves. The following indices were considered for each urban sub-area: Normalized Difference Vegetation, Proportion Vegetation, Normalized Difference Built, and Urban Index. The goal is to conduct a statistical analysis of the link between the aforementioned elements and the heat stress index in order to recommend mitigation and resilience techniques. Our findings showed that compact and industrial LCZs (2, 3, and 10) are less resistant to HI than open and rural regions (5, 6, B, D, and G), which are more resistant to HI due to higher vegetation rates. The heat wave condition exacerbates the HI in all LCZs. As a result, initiatives such as enhancing open space, increasing green space, or using green roofs and façades might alleviate heat stress and improve people’s quality of life.

Abstract P225: The Reninness Score: Integrative Analysis Of Multi-omic Data To Define Renin Cell Identity.

Renin cell (RC) descendants regain the endocrine renin phenotype to overcome homeostatic threats, a process known as recruitment. The determinants that control the identity, fate, and recruitment of RCs are not well understood. We aim to 1) define the chromatin pattern that determines RC identity; and 2) develop a computational tool to score samples by similarity to that pattern. We compared open chromatin regions (ATAC-seq) between non-renin-expressing (n = 184) and renin-expressing samples (n = 19) from three different sources and stimulation states: 1) primary RCs in basal state (WT); 2) primary RCs chronically stimulated to produce renin (recruited); and 3) constitutively renin-expressing tumoral cells. Differential analyses between the three types of RCs and the non-RCs revealed 1,525 unique open chromatin regions shared in at least two RC groups, including regions associated with RC-specific genes: Ren1 and Akr1b7. Increased accessibility regions in RC groups are enriched in renin-related GO terms ( e.g., cAMP and Notch signaling pathway). The bZip family ( e.g. , Atf3, p < 10 -2147 ) was the most enriched motifs in tumoral cells, and MEF2 family ( e.g. , MEF2a, p < 10 -91 ) in primary cells. Co-enriched motifs (e.g., MEIS1, p < 10 -10 ; NR4A2, p < 10 -9 ) in Ren1 and Akr1b7 regions suggest a group of TFs govern their co-expression. In addition, we identified unique open chromatin regions and enriched motifs ( e.g., E2F4, p < 10 -9 ; SP2, p < 10 -7 ) in recruited RCs, suggesting associated TFs involved in the recruitment.Next, we used a machine-learning approach to calculate a "reninness" score by training a genomic region model with renin and non-renin ATAC-seq data. We identified a cluster of regions (n = 112,992) around the trained renin label, which included 89% (21,820 of 24,612) of the increased accessibility regions from the differential analyses. We calculated the reninness score based on the distance between the trained label embeddings and predicted samples using the trained model. Homogeneous WT RCs had the highest score, followed by renin-expressing tumoral and primary cells. Non-RCs had the lowest score. In conclusion, we identified the chromatin configurations defining the identity and recruitment of RCs and developed a computational score to quantify it.

Association between acetaminophen metabolites and CYP2E1 DNA methylation level in neonate cord blood in the Boston Birth Cohort

BackgroundAcetaminophen is a commonly used medication by pregnant women and is known to cross the placenta. However, little is known about the biological mechanisms that regulate acetaminophen in the developing offspring. Cytochrome 2E1 (CYP2E1) is the primary enzyme responsible for the conversion of acetaminophen to its toxic metabolite. Ex vivo studies have shown that the CYP2E1 gene expression in human fetal liver and placenta is largely controlled by DNA methylation (DNAm) at CpG sites located in the gene body of CYP2E1 at the 5’ end. To date, no population studies have examined the association between acetaminophen metabolite and fetal DNAm of CYP2E1 at birth.MethodsWe utilized data from the Boston Birth Cohort (BBC) which represents an urban, low-income, racially and ethnically diverse population in Boston, Massachusetts. Acetaminophen metabolites were measured in the cord plasma of newborns enrolled in BBC between 2003 and 2013 using liquid chromatography-tandem mass spectrometry. DNAm at 28 CpG sites of CYP2E1 was measured by Illumina Infinium MethylationEPIC BeadChip. We used linear regression to identify differentially methylated CpG sites and the “DiffVar” method to identify differences in methylation variation associated with the detection of acetaminophen, adjusting for cell heterogeneity and batch effects. The false discovery rate (FDR) was calculated to account for multiple comparisons.ResultsAmong the 570 newborns included in this study, 96 (17%) had detectable acetaminophen in cord plasma. We identified 7 differentially methylated CpGs (FDR < 0.05) associated with the detection of acetaminophen and additional 4 CpGs showing a difference in the variation of methylation (FDR < 0.05). These CpGs were all located in the gene body of CYP2E1 at the 5’ end and had a 3–6% lower average methylation level among participants with detectable acetaminophen compared to participants without. The CpG sites we identified overlap with previously identified DNase hypersensitivity and open chromatin regions in the ENCODE project, suggesting potential regulatory functions.ConclusionsIn a US birth cohort, we found detection of cord biomarkers of acetaminophen was associated with DNAm level of CYP2E1 in cord blood. Our findings suggest that DNA methylation of CYP2E1 may be an important regulator of acetaminophen levels in newborns.

Natural Convection in Open Square Enclosure with Different Heat Source Sizes

In this study, a real-time experimental investigation is performed by a nonintrusive technique using a Mach-Zehnder interferometer. Experiments are performed in a partially open square enclosure with an internal heat source located at the center of bottom wall. The enclosure contains two openings at the bottom and top of the left and right vertical walls, respectively. The openings occupy 25% of the wall’s height. The experimental interferograms give temperature distribution in the investigating domain. The effect of heat source size and Rayleigh number on natural convection is evaluated experimentally, and the results are compared with numerical results obtained using ANSYS Fluent 2020. A dense fringe pattern is observed at larger heat source size and Rayleigh number. An air velocity transducer is used to measure inlet velocity and observe that high velocity air enters the cavity from bottom region of opening. Heat transfer and volume flow rate in the enclosure increase with increase in heat source size and Rayleigh number. Within the range of Rayleigh number 107 to 108, an increase in the heat source size by four times leads to an average increment in Nusselt number by about 33%, whereas the increment in volume flow rate is about 1%.

Single-cell genomics improves the discovery of risk variants and genes of atrial fibrillation

Genome-wide association studies (GWAS) have linked hundreds of loci to cardiac diseases. However, in most loci the causal variants and their target genes remain unknown. We developed a combined experimental and analytical approach that integrates single cell epigenomics with GWAS to prioritize risk variants and genes. We profiled accessible chromatin in single cells obtained from human hearts and leveraged the data to study genetics of Atrial Fibrillation (AF), the most common cardiac arrhythmia. Enrichment analysis of AF risk variants using cell-type-resolved open chromatin regions (OCRs) implicated cardiomyocytes as the main mediator of AF risk. We then performed statistical fine-mapping, leveraging the information in OCRs, and identified putative causal variants in 122 AF-associated loci. Taking advantage of the fine-mapping results, our novel statistical procedure for gene discovery prioritized 46 high-confidence risk genes, highlighting transcription factors and signal transduction pathways important for heart development. In summary, our analysis provides a comprehensive map of AF risk variants and genes, and a general framework to integrate single-cell genomics with genetic studies of complex traits.

Integrated 3D genome, epigenomeand transcriptome analyses reveal transcriptional coordination of circadian rhythm in rice.

Photoperiods integrate with the circadian clock to coordinate gene expression rhythms and thus ensure plant fitness to the environment. Genome-wide characterization and comparison of rhythmic genes under different light conditions revealed delayed phase under constant darkness (DD) and reduced amplitude under constant light (LL) in rice. Interestingly, ChIP-seq and RNA-seq profiling of rhythmic genes exhibit synchronous circadian oscillation in H3K9ac modifications at their loci and long non-coding RNAs (lncRNAs) expression at proximal loci. To investigate how gene expression rhythm is regulated in rice, we profiled the open chromatin regions and transcription factor (TF) footprints by time-series ATAC-seq. Although open chromatin regions did not show circadian change, a significant number of TFs were identified to rhythmically associate with chromatin and drive gene expression in a time-dependent manner. Further transcriptional regulatory networks mapping uncovered significant correlation between core clock genes and transcription factors involved in light/temperature signaling. In situ Hi-C of ZT8-specific expressed genes displayed highly connected chromatin association at the same time, whereas this ZT8 chromatin connection network dissociates at ZT20, suggesting the circadian control of gene expression by dynamic spatial chromatin conformation. These findings together implicate the existence of a synchronization mechanism between circadian H3K9ac modifications, chromatin association of TF and gene expression, and provides insights into circadian dynamics of spatial chromatin conformation that associate with gene expression rhythms.

How useful are mispointing phase SARAL/AltiKa geophysical products for ocean applications?

SARAL/AltiKa, the first microwave altimeter operating at Ka-band frequency, recently completed nine years of operations in orbit. During these years, it has catered to many applications related to operational oceanography, climate sciences, hydrology and cryosphere. More specifically, in oceanography, SARAL has contributed immensely to operational wave and circulation modelling, eddy detection/tracking, ocean current generation and many more. However, since Feb 2019, SARAL has moved from the drifting phase (DP) to the mispointing phase (MP) due to the malfunctioning of the star sensor of the spacecraft. In this study, we analyse the instrument’s performance and its waveforms during its ongoing MP. We find out that during the MP, significant wave height (SWH) measurements are anomalously high between 18 and 24 m, and wind speed measurements are between 16 and 19 m/s. In sea surface height anomaly (SSHA), there is a steady rise in negative values during the MP. In the return waveform, ∼15% degradation in Brown-type waveforms in the open ocean region is noticed. These changes significantly impact the SARAL applications. Two important applications of wave forecast and eddy detection are discussed here as examples. Following this, we also recommend using provided quality flags so that the data can be further explored for various ocean applications.

ATAC-seq: A powerful tool for investigating chromatin accessibility and transcription factor binding

Chromatin Transposase Accessibility Sequencing is a new high-throughput sequencing technique developed by Professor William Greenleaf in 2013 which uses DNA transposase to probe chromatin accessibility with Tn5 transposase. This technique, which is simpler and more sensitive than DNase-seq, MNase-seq and FAIRE-seq and requires fewer cells, has been used to study chromatin accessibility using Tn5 transposase. ATAC-seq is important for the study of epigenetic molecular mechanisms because it can map chromatin accessibility on a genome-wide scale, compare open chromatin regions in different tumour samples, compare differences in transcription factor binding between treatments, reveal nucleosome localisation information and transcription factor binding sites, and can be used to locate specific unknown transcription factors, which can be used in combination with other methods to screen for specific transcription factors of interest. It is possible to combine this approach with others to investigate specific regulatory factors. Herein, ATAC-seq is systemically profiled to present that ATAC-seq has enormous potential to drive future discoveries in the field of genomics and beyond.

Attributing near-surface atmospheric trends in the Fram Strait region to regional sea ice conditions

Abstract. Arctic sea ice has declined in all seasons accompanied by rapid atmospheric warming. Here, the focus lies on the wider Fram Strait region where the connection between trends in observed near-surface variables (temperature, humidity, wind speed) and local sea ice conditions are analyzed. Reanalysis data from ERA5 and MERRA-2 and Special Sensor Microwave/Imager ARTIST Sea Ice (SSM/I-ASI) sea ice concentrations for the winters of 1992 to 2022 are used for the analyses. Two focus regions are identified for which trends are largest. In the western Nansen Basin (WNB), sea ice cover decreased by −10 % per decade with especially large open water areas in 2022, and temperature and humidity increased by up to 3.7 K and 0.29 g kg−1 per decade, respectively. In the Greenland sea region (GRL), trends were slightly smaller, with −4.7 % per decade for sea ice and up to 1.3 K and 0.15 g kg−1 per decade for temperature and humidity. Trends for wind speed were mostly not significant. As a next step, two typical flow directions for this region were studied: cold-air outbreaks with northerly winds originating from ice covered areas (off-ice flow) and warm-air intrusions with southerly winds from open ocean regions (on-ice flow). To identify possible relationships between sea ice changes and atmospheric trends, correlation maps were calculated, and the results for off- and on-ice flow were compared. Up to two thirds of the observed temperature and humidity variability in both regions are related to upstream sea ice variability and an influence of sea ice cover is still present up to 500 km downstream of the ice edge. In the marginal sea ice zone the impact of a decreasing sea ice cover in this region is largest for off-ice flow conditions during cold-air outbreaks.

Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells.

i-Motifs (iMs) are four-stranded DNA structures that form at cytosine (C)-rich sequences in acidic conditions in vitro. Their formation in cells is still under debate. We performed CUT&Tag sequencing using the anti-iM antibody iMab and showed that iMs form within the human genome in live cells. We mapped iMs in two human cell lines and recovered C-rich sequences that were confirmed to fold into iMs in vitro. We found that iMs in cells are mainly present at actively transcribing gene promoters, in open chromatin regions, they overlap with R-loops, and their abundance and distribution are specific to each cell type. iMs with both long and short C-tracts were recovered, further extending the relevance of iMs. By simultaneously mapping G-quadruplexes (G4s), which form at guanine-rich regions, and comparing the results with iMs, we proved that the two structures can form in independent regions; however, when both iMs and G4s are present in the same genomic tract, their formation is enhanced. iMs and G4s were mainly found at genes with low and high transcription rates, respectively. Our findings support the in vivo formation of iM structures and provide new insights into their interplay with G4s as new regulatory elements in the human genome.

Outgassing of CO2 dominates in the coastal upwelling off the northwest African coast

The Eastern Boundary Upwelling System off northwest Africa is among the most productive regions of the ocean. In 2019, two merchant ships equipped with an underway CO2 system sampled the region following exactly the same track from 10°N to 36°N. We determine the sources and sinks of CO2 and the seasonal cycle along the track. A weak permanent upwelling (WPU), a permanent upwelling (PU) and an open ocean regions are identified. The WPU (26°N to 33°N) is a source of CO2 in summer and autumn, and a sink of CO2 in winter and spring. Thermodynamic warming and cooling processes mainly drive the CO2 variations in this region. The PU (20°N to 26°N) is a sink of CO2 in spring and a source of CO2 in other seasons. This region is the most productive and exhibits the largest variability of the CO2 flux. The supply of CO2 from subsurface waters dominate over the carbon uptake by biology, which leads to a strong outgassing, especially in winter and autumn. A sink of CO2 occurs in spring only in the PU. Near Cape Blanc (20°N) in July 2019, a source of CO2 is observed around 20°N within ± 1° of latitude and becomes a sink of CO2 a few days later when the ship samples back the same area. South of 18°N, out of the influence of the coastal upwelling, the region is a sink of CO2 in winter only and the region is mainly controlled by physical processes. Using voyages from 2010 to 2022, seawater fCO2 significantly increases at a rate ranging from 1.82 μatm yr−1 to 2.10 μatm yr−1 close to the atmospheric increase. This is associated with a pH decrease between 0.0016 and 0.0022 yr−1. Nevertheless, there is no clear trend of the CO2 flux in any region.

Improving SAR wind retrieval through automatic anomalous pixel detection

Satellite observations are increasingly in demand and valuable for monitoring the ocean and coastal winds in near-real-time and analyzing the data historically. However, soared up human activities, man-made constructions, and marine traffics negatively interfere and affect the reliability of observations and raise concerns about the trustworthiness of using satellite winds for many applications, such as offshore wind energy, even though Sentinel synthetic aperture radar (SAR) data is freely and easily accessible.In this paper, we presented a novel methodological framework for localization and suppression of anomalous pixels (APs), which deteriorate the confidence and accuracy of the retrieved SAR wind speeds. The backbone of the implementation relied on the constant false alarm rate (CFAR) algorithm, one of the automatic target recognition algorithms. We used a large dataset of SAR subscenes to model different sea clutter conditions after removing the potential targets. We selected the suitable distribution model that maintains a constant probability of false alarm (pfa) for the entire SAR scene. The proper pfa was optimized in various SAR scenes ranging from scenes with a considerable number of APs, such as ships and wind park clusters, to scenes with no visible APs under different wind speed conditions. The pfa optimization process prevented real wind pixels from being misidentified as APs.Applying CFAR to the logarithmic scale of raw digital numbers (log-DNs) domain with a pfa of about 3.17 × 10-5, we extracted SAR wind speeds around each ocean buoy before and after CFAR process, comparing them with their corresponding in situ wind measurements. This led to significant improvement in the quality and accuracy of SAR wind data retrieval, especially in regions with numerous man-made constructions and high marine traffics. We tested and validated our approach in the North Sea and two regions along the eastern coast of the U.S. The enclosed region, serving as a marine route for harbors in Delaware Bay, showed a substantial improvement in RMSE and BIAS after applying our approach, reducing RMSE from 2.4 m/s to 1.6 m/s and the BIAS from −1.5 m/s to −0.3 m/s. The open ocean region demonstrated stable RMSE and BIAS, indicating preservation of real wind data, as only APs affecting SAR wind speed were considered during the process.

The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes

Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.

Geopolitical Competition Among Great Powers and ASEAN’s Policy Preference

The United States has long been a security ally and economic partner of ASEAN members. The strengths of the U.S.-ASEAN partnership include cooperation on regional security, economic growth, and people-to-people ties. The United States also supports ASEAN's efforts to promote regional cooperation and integration through mechanisms such as the ASEAN Regional Forum and the East Asia Summit. Moreover, the United States has demonstrated its commitment to maintaining a free and open Indo-Pacific region, which is consistent with ASEAN's own desire for a rules-based regional order. Due to its strategic presence in the Asia-Pacific region, the United States is considered to play a very important role in ASEAN's soft balance against China. ASEAN's hedging approach and bandwagoning are no longer relevant in the context of rising competition between China and the United States. This paper will explain the causes of China and ASEAN's lack of political and security cooperation. By combing and evaluating current literature discussing the political and security cooperation between ASEAN and ASEAN countries with China and the United States. ASEAN's security policy against China, in particular. This paper's main research method is to explain the adjustment of ASEAN's policy toward China in the context of great power geopolitics through the soft balance theory by analyzing the political and security cooperation between ASEAN and China and the United States, as well as the weapons imported by ASEAN countries from China and the United States.

Different vertical heat transport induced by submesoscale motions in the shelf and open sea of the northwestern South China Sea

Submesoscale currents are known to be associated with strong vertical velocities (O (10) m/day), regulating the redistributions of energy and matter balances. The northern South China Sea (SCS) is fulfilled with submesoscale motions, which might induce strong vertical heat transport (VHT). We set up a 1-km horizontal resolution Massachusetts Institute of Technology General Circulation Model (MITgcm) to study the seasonal variations in submesoscale vertical heat transport in shelf regions and open seas. Spectrum analysis shows that the spatial scale separating submesoscale and mesoscale motions are 14 and 30 km for the shelf and open regions, respectively. The submesoscale VHT in the shelf region is one order of magnitude larger than that in the open ocean. The former has the largest value in summer and winter, which might be induced by summer upwelling and winter downwelling, while the latter is strongest in winter and weakest in summer in open regions. The submesoscale VHT also appears to have intra-seasonal variations and might be attributed to the disturbances of tropical cyclones and life stages of submesoscale eddies. The submesoscale VHT is strongest in the pregeneration phase of the eddies, and the maximum VHT belt has an entrainment type at the developing and mature stages. The chlorophyll-a concentration also has the same temporal variation as the different life-stage of eddies. This study provides local VHT induced by submesoscale motions, which is expected to improve our understanding of submesoscale air–sea interactions and their biological effects.

Exploring the discrepancy between top-down and bottom-up approaches of fine spatio-temporal vehicular CO2 emission in an urban road network

Road transport emissions of high spatial and temporal resolution are useful for greenhouse gas emission assessment in local action plans. However, estimating these high-resolution emissions is not straightforward, and different indirect approaches exist. The main aim of this study is to examine the differences in CO2 emissions obtained with different methods within a street canyon network in Helsinki, Finland, where a mobile laboratory campaign to quantify traffic emissions has been conducted. We compared three aerodynamic resistance based top-down methods (MOST1, MOST2 and BHT) and three activity based bottom-up microscopic emission models (NGM, HBEFAv4.2 and PHEMlight). The resulted CO2 fluxes using different methods could vary a few orders of magnitude. The combination of MOST1 and NGM model leads to the smallest discrepancy (sMAPE = 16.90 %) and the highest correlation coefficient (r = 0.78) among the rest. We evaluated the discrepancies in terms of different spatial (microenvrionments, local climate zones LCZs and grid sizes) and temporal features (seasons and periods of day). Measurements taken in LCZs of open high-rise regions and microenvironments of main road tend to have larger discrepancies between the two approaches. Using a coarser grid would lead to a relatively small discrepancy and high correlation in the wintertime, yet a loss in distinctive spatial variation. The discrepancies were also elevated on winter evenings. Among all explanatory variables, relative humidity shows the strongest relative importance for the discrepancy of the two approaches, followed by LCZs. Therefore, we stress the importance of choosing a suitable model for vehicular CO2 emission calculation based on meteorological conditions and LCZs. Such model comparison made on a local scale directly supports environmental organisations and cities' climate action plans where detailed information of CO2 emissions are needed.

High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes

Most of the single-nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to evaluate the regulatory activities of 5,987 noncoding SNPs associated with IR-relevant phenotypes. We identified 876 SNPs with biased allelic enhancer activity effects (baaSNPs) across 133 loci in three IR-relevant cell lines (HepG2, preadipocyte, and A673), which showed pervasive cell specificity and significant enrichment for cell-specific open chromatin regions or enhancer-indicative markers (H3K4me1, H3K27ac). Further functional characterization suggested several transcription factors (TFs) with preferential allelic binding to baaSNPs. We also incorporated multi-omics data to prioritize 102 candidate regulatory target genes for baaSNPs and revealed prevalent long-range regulatory effects and cell-specific IR-relevant biological functional enrichment on them. Specifically, we experimentally verified the distal regulatory mechanism at IRS1 locus, in which rs952227-A reinforces IRS1 expression by long-range chromatin interaction and preferential binding to the transcription factor HOXC6 to augment the enhancer activity. Finally, based on our STARR-seq screening data, we predicted the enhancer activity of 227,343 noncoding SNPs associated with IR-relevant phenotypes (fasting insulin adjusted for BMI, HDL cholesterol, and triglycerides) from the largest available GWAS summary statistics. We further provided an open resource (http://www.bigc.online/fnSNP-IR) for better understanding genetic regulatory mechanisms of IR-relevant phenotypes.

Epigenetic modification related to cognitive changes during a cognitive training intervention in depression

BackgroundDNA methylation as a biomarker is well suited to investigate dynamic processes, such as symptom improvement. For this study we focus on epigenomic state or trait markers as early signatures of cognitive improvement in individuals receiving a cognitive intervention. We performed a first epigenome-wide association study (EWAS) on patients with cognitive dysfunction in depression comparing those with vs without cognitive dysfunction and those cognitively improving vs non-improving following a cognitive intervention. MethodData from a randomized controlled trial (RCT) were used for this analysis, where cognitive function of 112 patients randomly assigned to a personalized cognitive intervention was compared to standard cognitive treatment. Cognition was measured for this study using the four cognitive tasks from the THINC-it battery. We compared individuals with cognitive impairment with individuals without cognitive impairment at baseline and after a cognitive intervention of 8 weeks. Blood for DNA methylation analysis (Illumina Infinium MethylationEPIC 850 k BeadChip) was collected at baseline and 8 weeks into the treatment. For the baseline analysis, after quality control, the final sample comprised 90 individuals, and analyses at week 8 were performed on 84 individuals. Data cleaning, quality control, and differential methylation analysis of DNA methylation data was performed using the RnBeads package (R). Analyses were corrected for gender, age, depression score (MADRS), reported years of education, height and weight, as well as surrogate variables estimated by the pipeline used. The within-individual paired longitudinal analysis was performed using Welch's t-test. ResultsAnalyses at baseline and at week 8 did not show any genome-wide significant CpGs (p < 5 × 10−8) comparing patients with and without cognitive impairment. The most significant result in the baseline analysis comparing the groups with and without cognitive impairment at baseline is located in an open Sea region with predominantly regulatory qualities (cg10962945; 6.61 × 10−7). The most significant CpG at 8 weeks was also located in open sea, though in exon 13 of the NTRK2-gene, linked to the BDNF pathway (cg13620631, 5.56 × 10−7). Finally, a within-individual paired longitudinal analysis with only patients that show improved cognitive function over time was performed, showing 65 CpGs that overlapped between the 1% most significant of this analysis and the 1% most significant CpGs from the cross-sectional analysis at 8 weeks. ConclusionOur result suggest that DNA methylation can be suitable to capture early signs of treatment response of a cognitive intervention in depression. In our layered approach we could capture dynamics that can help differentiate between biological trait and state markers of cognitive function in depression. Despite not being genome-wide significant, the CpG locations returned by our analysis comparing patients with and without cognitive impairment, are in line with prior knowledge on pathways and genes relevant for depression treatment and cognition.

The Weddell Gyre heat budget associated with the Warm Deep Water circulation derived from Argo floats

Abstract. The Weddell Gyre plays an important role in the global climate system by supplying heat to underneath the ice shelves and in the formation of deep and bottom water masses, which have been subject to widespread warming over past decades. In this study, we investigate the re-distribution of heat throughout the Weddell Gyre by diagnosing the terms of the heat conservation equation for a 1000 m thick layer of water encompassing the core of Warm Deep Water. The spatial distributions of the different advective and diffusive terms in terms of heat tendencies are estimated using gridded climatologies of temperature and velocity, obtained from Argo floats in the Weddell Gyre from 2002 to 2016. While the results are somewhat noisy on the grid scale and the representation of the effects of eddy mixing is highly uncertain due to the need to parameterise them by means of turbulent diffusion, the heat budget (i.e. the sum of all terms) closes (within the uncertainty range) when integrated over the open inflow region in the southern limb, whereas the interior circulation cell remains unbalanced. There is an overall balance in the southern limb between the mean horizontal advection and horizontal turbulent diffusion of heat, whereas the vertical terms contribute comparatively little to the heat budget throughout the Weddell Gyre. Heat convergence due to mean horizontal advection balances with divergence due to horizontal turbulent diffusion in the open southern limb of the Weddell Gyre. In contrast, heat divergence due to mean horizontal advection is much weaker than convergence due to horizontal turbulent diffusion in the interior circulation cell of the Weddell Gyre, due to large values in the latter along the northern boundary due to large meridional temperature gradients. Heat is advected into the Weddell Gyre along the southern limb, some of which is turbulently diffused northwards into the interior circulation cell, while some is likely turbulently diffused southwards towards the shelf seas. This suggests that horizontal turbulent diffusion plays a role in transporting heat both towards the gyre interior where upwelling occurs and towards the ice shelves. Horizontal turbulent diffusion is also a mechanism by which heat can be transported into the Weddell Gyre across the open northern boundary. Temporal deviations from the mean terms are not included due to study limitations. In order to appreciate the role of transient eddying processes, a continued effort to increase the spatial and temporal coverage of observations in the eastern Weddell Sea is required.

On the Location of Chromatic Zeros of Series-Parallel Graphs

In this paper we consider the zeros of the chromatic polynomial of series-parallel graphs. Complementing a result of Sokal, giving density outside the disk $|q-1|\leq1$, we show density of these zeros in the half plane $\Re(q)&gt;3/2$ and we show there exists an open region $U$ containing the interval $(0,32/27)$ such that $U\setminus\{1\}$ does not contain zeros of the chromatic polynomial of series-parallel graphs.&#x0D; We also disprove a conjecture of Sokal by showing that for each large enough integer $\Delta$ there exists a series-parallel graph for which all vertices but one have degree at most $\Delta$ and whose chromatic polynomial has a zero with real part exceeding $\Delta$.