Depletion Patterns Research Articles

Distinct Chromatin Accessibility Profiles of Lymphoma Subtypes Revealed By Targeted Cell Free DNA Profiling

BackgroundDiffuse large B-cell lymphomas (DLBCL) can be divided into subtypes that relate to their cell-of-origin: germinal center B-cell (GCB) and activated B-cell (ABC). These clinically distinct subtypes were originally discovered based on their unique transcriptional signatures, but they also harbor distinct genetic aberrations and epigenetic profiles. We previously showed the utility of genetic mutations in circulating tumor DNA (ctDNA) for DLBCL subtyping using cancer personalized profiling by deep sequencing (CAPP-Seq) [Scherer et al., Sci Transl Med 2016, Newman et al., Nat Med 2014]. Here, we assess epigenetic information encoded in cell-free DNA (cfDNA) for addressing this distinction.MethodsWe extended recent observations revealing nucleosome depletion at transcription start sites (TSS) of highly expressed genes within cfDNA [Snyder et al. 2016 Cell and Ulz et al. 2016 Nat Genetics]. Specifically, to overcome the inherent sensitivity limitations of cfDNA whole genome sequencing (WGS), we focused on 32 genes differentially expressed between DLBCL subtypes (as well as 70 control genes). We targeted 2 kb regions flanking each TSS for these genes by CAPP-Seq [Newman et al. 2014 Nature Med]. Plasma samples were collected from 41 individuals and cfDNA subjected to ultra-deep sequencing (~4000x) by CAPP-Seq. DLBCL cases were labeled as either ABC or GCB based on gene expression in tumor biopsies.ResultsWe observed significant heterogeneity in the TSS profiles of individual genes. Despite this variation, many genes in our targeted panel exhibited discriminatory profiles. For example, CD20 (MS4A1), reliably distinguished DLBCL cases from control subjects in nucleosome depletion at the TSS as expected (p= 1.5e-05, Fig1a). Remarkably, when considering 32 genes differentially expressed between DLBCL subtypes, we observed significant differences in their TSS profiles in plasma from patients with GCB vs ABC DLBCL (p=0.0002, Fig 1b). For the majority of the subtype-specific genes, the pattern of nucleosome depletion at the TSS was consistent with expected expression (Fig 1b). Specifically, genes typically over-expressed in GCB DLBCL (e.g., CD10/MME, LMO2, SERPINA9), had significantly more TSS nucleosome depletion in cfDNA from GCB-like DLBCL patients. Conversely, we observed significantly more nucleosome depletion in cfDNA of ABC DLBCL patients at the TSS of genes known to be transcriptionally more active in ABC DLBCL (e.g., IRF4, PIM1, CCND2 and IL16). When aggregating the epigenetic profiles across these genes into a single cell-of-origin score, we observed significant stratification of patients with distinct DLBCL subtypes (Fig 1c, p=0.008). Across the cohort, this epigenetic cell-of-origin score from cfDNA showed significant correlation (Spearman rho=0.67, p=0.05) with a score derived from somatic mutations genotyped from ctDNA [Scherer et al. 2016 Sci Transl Med].ConclusionsLymphoma subtypes exhibit distinct chromatin accessibility profiles that can be captured by targeted cell free DNA profiling, and that can serve as surrogates for expected gene expression differences. These epigenetic features can be used to noninvasively classify DLBCL molecular subtypes using blood plasma and should be readily extensible to other cancer classification problems. Extension of this approach to other epigenetic features could serve to further refine potential applications.Figure legend.Figure 1. (A) Sequencing coverage around the TSS of the B-cell antigen CD20 (MS4A1) is shown for three representative DLBCL patients (red) and three normal controls (gray). The boxplot shows summary of normalized depth across all samples (n=10 DLBCL, n=31 control). (B) The y-axis shows 32 genes with known ABC-favoring (blue) and GCB-favoring (orange) expression. The x-axis shows a delta score defined as log2( mean normalized depth across GCB samples - mean normalized depth across GCB samples). (C) Boxplot of the GCBness score obtained by subtracting the overall depth around the TSSs of a set of GCB-genes from the same metric for a set of ABC-genes. DisclosuresNo relevant conflicts of interest to declare.

Ovarian ageing and the impact on female fertility.

Female fertility decreases with increasing age, a reflection of declining oocyte quantity and quality. The menopausal transition occurs when the oocyte quantity falls below a threshold level. The pattern of follicular depletion as well as the factors, timing and mechanisms surrounding both declining oocyte number and oocyte quality remain incompletely understood. Further studies are needed to examine the factors involved and develop predictive models and biomarkers to assist in the management of age-related subfertility. This review summarises the current knowledge addressing the ageing ovary and its impact on fertility.

The Pattern of Striatal Dopamine Depletion as a Prognostic Marker in De Novo Parkinson Disease

To investigate whether the patterns of striatal dopamine depletion could provide prognostic information on the clinical profiles of early-stage Parkinson disease (PD). Approximately 634 patients with drug-naive PD who underwent F-FP-CIT PET scans were followed up for at least 2 years. After quantifying dopamine transporter (DAT) availability in each striatal subregion, the patterns of striatal dopamine depletion of each patient were assessed based on (1) the degree of dopamine loss in the other striatal subregions compared to the posterior putamen (inter-subregional ratio [ISR]) and (2) the interhemispheric asymmetry of dopamine loss in the posterior putamen (asymmetry index [AI]). According to their patterns, we assessed the longitudinal changes in L-dopa-equivalent doses and L-dopa-induced dyskinesia (LID)-free times using the linear mixed model and Cox regression model, respectively. There was no significant correlation between the ISR and AI values (Pearson correlation coefficient, 0.150). The linear mixed model showed that higher AI values were associated with slower longitudinal increases in L-dopa-equivalent dose across time (P = 0.003), whereas ISR values were not (P = 0.154). The Cox regression model demonstrated that higher ISR values were associated with early development of LID (hazard ratio, 1.693; P = 0.010), whereas AI values were not (P = 0.269). The present study demonstrated that the pattern of anterior-to-posterior gradient and right-to-left asymmetry of striatal DAT availability predicted the development of LID and increasing doses of dopaminergic medications.

Interpreting element addition and depletion at the Ann Mason porphyry-Cu deposit, Nevada, using mapped mass balance patterns

Elemental mass changes were calculated for 154 samples from four rock types around the Ann Mason porphyry-Cu-(MoAu) deposit, Yerington district, Nevada. The purpose of these calculations was to investigate addition and depletion patterns in two-dimensional (2-D) map space. Mass changes in Ca, Mg, Na, P, Cu, Mo, As, Sb, Sr, and Pb from samples in the pre- to syn-mineralisation Yerington batholith vary systematically with lateral and vertical distance from the Ann Mason deposit. At the core of the Ann Mason deposit, Cu and Mo were strongly added (>10,000% relative to average protolith values), with restricted lateral mass addition halos around the deposit. Copper is depleted in wall rocks surrounding the deposit. Calcium and Sr were removed (up to 98% depletion) from parts of the deposit centre due to the destruction of calcic-plagioclase and other calcium-bearing minerals during potassic alteration. Calcium (up to 1570%) and Sr (up to 315%) were added outside the deposit and were concentrated around 4 km from the deposit centre where epidote alteration is most intense. Arsenic and Sb were removed from the deposit centre (up to 99% depletion) where silicate-mineral alteration assemblages dominate. Antimony shows an addition halo (ranging from 25% up to 1900%) that extends from the deposit centre 500 m laterally away, and correlates spatially with the increased abundance of pyrite that typically surrounds porphyry deposits. Epidote-altered samples of Shamrock monzonite from outside the Casting Copper skarn show addition of Ca (up to 196%), Sb (up to 1100%), and depletion of Na (up to −98%). Samples from the central part of the post-mineralisation Shamrock monzonite record lower mass changes in Mg, Ca, P, and Mo, compared to other parts of the batholith. Some samples from the northern contact of the Shamrock batholith exhibit addition of Ca (up to 554%), Sr (up to 504%), and depletion in Na (up to −98%). These samples are coincident with strong epidote alteration.Our results provide a rock-normalised geochemical map that reflects quantified element addition and depletion patterns, which is useful for interrogating geological processes at a regional scale. Although interpreting relative element addition and depletion in map space is possible using conventional immobile element ratio approaches, mass balance calculations provide the benefit of quantified results.

Constraining Gas-phase Carbon, Oxygen, and Nitrogen in the IM Lup Protoplanetary Disk

Abstract We present new constraints on gas-phase C, N, and O abundances in the molecular layer of the IM Lup protoplanetary disk. Building on previous physical and chemical modeling of this disk, we use new ALMA observations of C2H to constrain the C/O ratio in the molecular layer to be ∼0.8, i.e., higher than the solar value of ∼0.54. We use archival ALMA observations of HCN and H13CN to show that no depletion of N is required (assuming an interstellar abundance of 7.5 × 10−5 per H). These results suggest that an appreciable fraction of O is sequestered in water ice in large grains settled to the disk midplane. Similarly, a fraction of the available C is locked up in less volatile molecules. By contrast, N remains largely unprocessed, likely as N2. This pattern of depletion suggests the presence of true abundance variations in this disk, and not a simple overall depletion of gas mass. If these results hold more generally, then combined CO, C2H, and HCN observations of disks may provide a promising path for constraining gas-phase C/O and N/O during planet-formation. Together, these tracers offer the opportunity to link the volatile compositions of disks to the atmospheres of planets formed from them.

Spectrophotometric analysis of lipid used to examine the phenology of the tick Ixodes ricinus

BackgroundTicks store lipid as an energy souce, which depletes progressively between blood meals. The amount of lipid and rate of lipid depletion can be used as a good indicator of the feeding history and assist in explaining the phenology of tick populations. However, existing gravimetric approaches to lipid measurement are relatively imprecise. To improve our ability to accurately measure lipid accumulation and metabolism in individual ticks, a microquantity colorimetric sulfophosphovanillan method of lipid estimation was standardised and used to explore the seasonal variations in the lipid content of I. ricinus nymphs.ResultsLipid values for field-derived questing ticks, collected by blanket dragging, varied between 5–45 μg and clear patterns of lipid depletion were demonstrated under controlled laboratory conditions. For field populations collected monthly over two years, the results indicate that two different cohorts of nymphs enter the questing tick population in autumn and spring, with very few nymphs joining the population in summer.ConclusionsThe data illustrate the seasonal change in lipid content of nymphal ticks, reflecting their feeding history and highlight the utility of the spectrophotometric technique for analysis of lipid in ticks in helping to improve our understanding of seasonal activity patterns.

Geochemistry and apatite U–Pb geochronology of alkaline gabbros from the Nodoushan plutonic complex, Sanandaj–Sirjan Zone, Central Iran: Evidence for Early Palaeozoic rifting of northern Gondwana

The Zagros Orogen formed during the Cenozoic collision of Arabia with Eurasia and resulted in the closure of the Neo‐Tethys Ocean. Collision was preceded by a complicated tectonic history involving Pan‐African orogenesis, Late Palaeozoic rifting and the formation of Neo‐Tethys, and subsequent Mesozoic convergence on the northern margin of the ocean contemporaneous with ophiolite obduction on its southern margin. The Sanandaj–Sirjan Zone (SaSZ) is a metamorphic belt within the Zagros Orogen of Gondwanan provenance. U–Pb zircon geochronology has revealed the presence of Pan‐African igneous and metamorphic basement complexes, in addition to minor late Palaeozoic plutons and abundant Jurassic plutonic rocks. This study presents a LA‐ICP‐MS U–Pb apatite age of 440.7 ± 3.7 Ma from a gabbroic body on the central north‐eastern margin of the SaSZ (Nodoushan region). Based on petrography and geochemistry, en route fractional crystallization of ascending magma was an important process in the evolution of the intrusive rocks. Geochemical characteristics imply that the south‐west Nodoushan alkaline gabbroic magma was originated from the asthenospheric mantle source, whereas the high ratios of (La/Yb)N and (Dy/Yb)N are related to the low degree of partial melting from the garnet‐bearing mantle source. Enrichment pattern of Nb, Ta, and Ti and depletion of Rb, Th, and Y are similar to the OIB pattern and intraplate alkaline magmatic rocks. High εNd(t) values (+1.29 to +1.50), low initial Sr isotopic ratios (0.703679–0.704098), and trace element ratios (e.g., Nb/La, Ce/Pb, Ba/Nb, and Th/Nb) indicate that crustal contamination was insignificant in its petrogenesis. The petrogenesis of the Nodoushan alkaline gabbroic rocks could be related to the presence of extensional phase, upwelling and decompressional melting of asthenospheric mantle in the rift basin which was associated with the opening of the Paleo‐Tethys Ocean in Late Ordovician to Silurian times.

Three-dimensional super-resolution high-throughput imaging by structured illumination STED microscopy.

Stimulated emission depletion (STED) microscopy is able to image fluorescence labeled samples with nanometer scale resolution. STED microscopy is typically a point-scanning method, limited by the high intensity requirement of the depletion beam. With the development of high peak power lasers, two dimensional parallel STED microscopy has been developed. Here, we develop the theoretical basis for extending STED microscopy to three dimensional imaging in parallel. This method uses structured illumination (SI) to generates a three dimensional depletion pattern. Compared to the two dimensional parallel STED microscopy, the 3D SI-STED microscopy generates intensity modulation along the light propagation direction without requiring higher laser power. This method not only achieves axial super-resolution of STED microscopy but also greatly reduces photobleaching and photodamage for 3D volumetric imaging.

The chemical composition of carbonaceous chondrites: Implications for volatile element depletion, complementarity and alteration

In Earth and planetary sciences, the chemical composition of chondritic meteorites provides an essential reference to constrain the composition and differentiation history of planetary reservoirs. Yet, for many trace elements, and in particular for volatile trace elements the composition of chondrites is not well constrained. Here we present new compositional data for carbonaceous chondrites with an emphasis on the origin of the volatile element depletion pattern. Our database includes 25 carbonaceous chondrites from 6 different groups (CI, CM, CR, CV, CO, CK), two ungrouped carbonaceous chondrites and Murchison powder samples heated up to 1000 °C in O2 or Ar gas streams, respectively. A total of 51 major and trace elements were analyzed by sector field inductively coupled plasma mass spectrometry (SF-ICP-MS), using chondrite-matched calibration solutions. Our results confirm that parent body alteration and terrestrial weathering only have minor effects on the bulk chondrite compositions. Thermal metamorphism can lead to the loss of some volatile elements, as best observed in the heating experiments and two thermally overprinted chondrites Y-980115 (CI) and EET 96026 (CV4/5 or CK4/5). The effects of aqueous alteration and terrestrial weathering on the Antarctic samples are difficult to discriminate. Both processes may redistribute fluid mobile elements such as K, Na, Rb, U and the light rare earth elements (LREE) within the meteorite. In hot desert finds, the typical weathering effects are enrichments of Sr, Ba and U and a depletion of S.In general, moderately volatile elements with 50% condensation temperatures (TC) ranging from 1250 K to 800 K show an increasing depletion, whereas 11 moderately volatile elements with 50% TC between 800 K and 500 K are unfractionated from each other in most samples. Their extent of depletion is characteristic for the different chondrite groups. Because of this well-defined “hockey stick” pattern, we propose to divide the moderately volatile elements into two subgroups, the ‘slope volatile elements’ and the unfractionated ‘plateau volatile elements’ with lower TC. Notably, the abundances of plateau volatile elements exhibit a co-variation with the matrix abundances of the respective host meteorites. Carbonaceous chondrite matrices are likely mixes of: (i) CI-like material and (ii) chondrule-related matrix. Chondrule-related matrix is expected to be depleted in volatile elements relative to CI and likely formed contemporaneously with chondrules, leading to chondrule-matrix complementarity. The addition of CI-like material only changed the absolute elemental concentrations of bulk matrix and bulk chondrite, while refractory and main component element ratios such as Mg/Si remain unaffected. Such a model can also account for the co-existence of low temperature CI-like material and high temperature chondrule and chondrule-related matrix. However, elevated volatile element abundances observed in chondrules still provide a challenge for the model as proposed here.

Abstract 4996: MLL3 haploinsufficiency preserves self-renewal capacity in HSCs with extensive cumulative division histories

Abstract KMT2C/MLL3 is one of the most commonly mutated tumor suppressor genes in human cancer. Haploinsufficiency at the KMT2C/MLL3 locus often occurs in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) as a result of mono-allelic 7q deletions. Mll3 haploinsufficiency has been shown to accelerate AML in mice, but it is not clear how it regulates normal hematopoietic progenitors or why it is required to suppress leukemogenesis. We used a novel loss-of-function mouse allele to characterize hematopoiesis in Mll3-deficient fetal livers and adult bone marrow. Mll3 deletion caused a modest increase in fetal liver hematopoietic stem cells (HSCs) and a modest decrease in lineage restricted progenitors (HPCs). In contrast, Mll3 heterozygosity caused significant expansion of the HSC population in adult bone marrow without affecting more committed progenitor populations. Mll3+/- and Mll3-/- HSCs were able to repopulate lethally irradiated mice, and repopulating activity was enhanced in secondary and tertiary transplants relative to wild type HSCs. Thus, Mll3 haploinsufficiency enhances HSC self-renewal capacity. We next tested whether Mll3 regulates the balance between self-renewal and commitment in non-transplanted HSCs. We used H2B-GFP pulse-chase assays to assess the division histories of HSCs over time. After a 6-week chase, wild type HSCs retained high levels of H2B-GFP expression, consistent with prior studies showing that adult HSCs divide infrequently. In contrast, almost all Mll3+/- HSCs had low to moderate H2B-GFP expression levels, indicative of an extensive division history. This difference was not associated with an increase in the percentage of cycling (S/G2/M) HSCs, and it was not associated with a loss of self-renewal capacity that occurs with cumulative divisions in wild type HSCs. Thus, Mll3 haploinsufficiency allows cumulative HSC divisions to accrue without compromising self-renewal. Mll3 encodes a histone methyltransferase that binds active enhancers and promotes transcription. This raised the question of whether Mll3 deletion results in a loss of commitment-related gene expression, increased self-renewal gene expression or altered epigenetic landscapes. To our surprise, gene expression was indistinguishable between wild type and Mll3+/- HSCs. However, ATAC-seq analysis revealed patterns of nucleosome depletion in Mll3+/- HSCs that closely resembled wild type HPCs. No differences were observed in the ATAC-seq profiles of wild type and Mll3+/- HPCs. These observations suggest that as Mll3+/- HSCs self-renew, they remodel their epigenetic landscapes to resemble committed progenitors, yet they do not activate commitment related genes, and they do exit the stem cell pool. The data suggest that stress conditions that drive HSCs into cycle, such as the chemotherapy regimens that often precede 7q- MDS, may select for Mll3 haploinsufficient HSC clones. Citation Format: Theresa Owuor, Shaina Porter, Cluster Andrew, Riddhi Patel, Jeffrey Magee. MLL3 haploinsufficiency preserves self-renewal capacity in HSCs with extensive cumulative division histories [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4996.

Abundances and Depletions of Neutron-capture Elements in the Interstellar Medium

Abstract We present an extensive analysis of the gas-phase abundances and depletion behaviors of neutron-capture elements in the interstellar medium (ISM). Column densities (or upper limits to the column densities) of Ga ii, Ge ii, As ii, Kr i, Cd ii, Sn ii, and Pb ii are determined for a sample of 69 sight lines with high- and/or medium-resolution archival spectra obtained with the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope. An additional 59 sight lines with column density measurements reported in the literature are included in our analysis. Parameters that characterize the depletion trends of the elements are derived according to the methodology developed by Jenkins. (In an appendix, we present similar depletion results for the light element B.) The depletion patterns exhibited by Ga and Ge comport with expectations based on the depletion results obtained for many other elements. Arsenic exhibits much less depletion than expected, and its abundance in low-depletion sight lines may even be supersolar. We confirm a previous finding by Jenkins that the depletion of Kr increases as the overall depletion level increases from one sight line to another. Cadmium shows no such evidence of increasing depletion. We find a significant amount of scatter in the gas-phase abundances of Sn and Pb. For Sn, at least, the scatter may be evidence of real intrinsic abundance variations due to s-process enrichment combined with inefficient mixing in the ISM.

Effects of aberrations on effective point spread function in STED microscopy.

Like other imaging techniques, stimulated emission depletion (STED) microscopy suffers from aberrations. While their effects on depletion patterns have been explicitly investigated, the study on how aberrations affect the effective point spread function (PSF) in STED microscopy is still missing. For STED researchers, however, this study is beneficial, as it directly bridges image qualities and aberrations. In this paper, we quantitatively analyze the effects of primary aberrations, including astigmatism, coma, trefoil, and spherical aberration, in two-dimensional (2D) and three-dimensional (3D) STED microscopy, and further discuss the corresponding aberration tolerance. Specifically, attention is given to the modification of the shape, the size, and the peak intensity of the effective PSF in the presence of these aberrations.

Investigation of Ground Water Depletion Pattern across Chennai City

An attempt has been made to investigate both seasonal and long term ground water depletion pattern across the aquifers lying below geographical boundary of Chennai city. The Depth below Ground Level (DBGL) is used as an analyzing parameter for this investigation. This analysis is based on the data that has been made available to the public by Central Ground Water Board (CGWB) and Water Resources Department, Chennai, Tamil Nadu. Both graphical analysis and statistical based regression analysis has been carried out and the result has been presented in graphical and tabular form. Seasonal DBGL variation has been analyzed for the year 2016 after the popular Chennai 2015 December Flood event. It has been observed that the range of ground water level depletion is from 0.1 m per month at Broadway and up to 0.833 m per month at T.S.Campus locations during post monsoon season from January to May. Long term DBGL variation has been analyzed for duration of 22 years from 1996 to 2017. Statistical package for social sciences (SPSS) has been used to perform both linear and other regression analysis. Sustained decrease in ground water level has been observed at locations like Perambur Kodambakkam and Vallalar Nagar during the last two decades.

Performance of Turmeric and Soil Moisture Depletion Pattern Under Different Water Regimes and Nutrient Sources at New Alluvial Zone of Indo-Gangetic Plains, India

ABSTRACTIn India, the production of turmeric is not even half compared to its potential. To analyze the possibilities for higher production in turmeric, this study was conducted at the BCKV, Gayeshpur, West Bengal, during 2011 and 2012, to evaluate the effect of irrigation scheduling (0.6, 0.9, and 1.2 irrigation water (IW)/cumulative pan evaporation (CPE) and rainfed) in main plots and nutrient management [100% inorganic, 75% inorganic + 25% FYM (Farm yard manure), and 50% inorganic + 25% FYM + 25% vermicompost] in subplots on soil moisture depletion and productivity of turmeric. The highest value of fresh rhizome yield (23.90 kg ha−1) and qualitative indices were obtained with irrigation schedule at 0.9 IW/CPE ratio water regimes and 50% inorganic + 25% FYM + 25% vermicompost. The correlation coefficients of water use and yield of turmeric were found at 0.943. The combination of 0.9 IW/CPE and 50% inorganic + 25% FYM + 25% vermicompost improved the overall performance of turmeric crop.

Decreased Density of Cholinergic Interneurons in the Medial Caudate Nucleus in Humans with Williams Syndrome

Williams syndrome (WS) is a rare neurodevelopmental disorder caused by the hemideletion of approximately 25–28 genes at 7q11.23. Its unusual social and cognitive phenotype is most strikingly characterized by the disinhibition of social behavior, in addition to reduced global IQ, with a relative sparing of language ability. Hypersociality and increased social approach behavior in WS may represent a unique inability to inhibit responses to specifically social stimuli, and is likely rooted in part in abnormalities of frontostriatal circuitry. Recent research has demonstrated that selective ablation of striatal cholinergic interneurons (SCINs) results in significant increases in compulsive conspecific‐directed, but not object‐focused, exploratory behavior in mice, indicating a role for SCINs in social approach behavior. Here, we examined the density of SCINs and parvalbumin‐positive interneurons in the striatum of five postmortem specimens from subjects with WS and five typically‐developing (TD) subjects. We found a significant reduction in the density of SCINs in the medial caudate nucleus, an important region receiving cortical projections from the orbitofrontal and ventromedial prefrontal cortex in circuitry involved in language and reward systems. This pattern of decreased SCIN density in WS is contrasted by anatomical findings in other disorders, including Tourette syndrome and schizophrenia, where differing patterns of SCIN depletion are found. Taken together with findings from neuroimaging, differences in the brains of individuals with WS at both the macro‐ and microstructural level further indicate a role for frontostriatal circuitry in the disorder's distinctive behavioral phenotype.Support or Funding InformationThis research is supported in part by NIH #P01NICHD033113, #1R03MH103697‐01(KS), and a Wenner Gren Dissertation Fieldwork Grant (KLH).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Soil water depletion patterns of artificial forest species and ages on the Loess Plateau (China)

Afforestation as an effective measure to control soil erosion has achieved remarkable effects in northern China. However, large scale of artificial afforestation can increase soil water consumption and induce soil desiccation in arid and semi-arid areas. This study analyzed the variations of soil water storage following the conversion of croplands into forests with different species and stand ages on the Loess Plateau. Three most common artificial forests dominated by Salix matsudana, Populus cathayana, and Sophora japonica with stand ages of 5, 10, and 15 years were investigated to determine the variations in soil water storage. The results showed that soil water storage decreased with increasing afforestation ages and soil depth. Salix matsudana mainly consumed shallow soil water (0–100 cm), P. cathayana mainly consumed deep soil water (100–150 cm), while S. japonica had relatively lower water consumption than the other two species. Converting cropland into forest resulted in a significant water deficit. Soil water deficit in the 0–100 cm soil profiles was significantly higher under S. matsudana than under the other two artificial forests. Severe soil water depletion and obvious soil desiccation occurred after 12 years of afforestation. Therefore, artificial forests with less water consumption, e.g. S. japonica, should be given priority in future afforestation practice. To maintain the sustainability of vegetation, changes in land-use patterns should be considered after 12 years of afforestation.

In vivo quantification of plant starch reserves at micrometer resolution using X-ray microCT imaging and machine learning.

Starch is the primary energy storage molecule used by most terrestrial plants to fuel respiration and growth during periods of limited to no photosynthesis, and its depletion can drive plant mortality. Destructive techniques at coarse spatial scales exist to quantify starch, but these techniques face methodological challenges that can lead to uncertainty about the lability of tissue-specific starch pools and their role in plant survival. Here, we demonstrate how X-ray microcomputed tomography (microCT) and a machine learning algorithm can be coupled to quantify plant starch content invivo, repeatedly and nondestructively over time in grapevine stems (Vitis spp.). Starch content estimated for xylem axial and ray parenchyma cells from microCT images was correlated strongly with enzymatically measured bulk-tissue starch concentration on the same stems. After validating our machine learning algorithm, we then characterized the spatial distribution of starch concentration in living stems at micrometer resolution, and identified starch depletion in live plants under experimental conditions designed to halt photosynthesis and starch production, initiating the drawdown of stored starch pools. Using X-ray microCT technology for invivo starch monitoring should enable novel research directed at resolving the spatial and temporal patterns of starch accumulation and depletion in woody plant species.

Effect of striatal dopamine depletion on cognition in de novo Parkinson's disease

IntroductionTo investigate the relationship between the sub-regional pattern of striatal dopamine depletion and cognitive impairment in early-stage Parkinson's disease (PD), and determine the effect of striatal dopamine density on cognitive prognosis. MethodsPatients with drug-naïve non-demented PD were divided into mild cognitive impairment (PD-MCI; n = 129) and cognitively normal (PD-CogN; n = 182) groups. Using quantification of the dopamine transporter (DAT) availability in each striatal sub-region with 18F-FP-CIT PET scans, we performed inter-group comparative analysis of DAT availability and multivariate linear regression analysis to assess the association between DAT availability and cognitive performance. Additionally, the effect of baseline DAT availability on the cognitive decline across time as well as on changes in the cognitive status was estimated. ResultsThe PD-MCI group exhibited more severely decreased DAT availability in all the striatal sub-regions compared to the PD-CogN group, although there was no significant difference in PD duration. The DAT availability in the caudate, anterior putamen, and ventral striatum was directly associated with attention/working memory, frontal/executive, and visuospatial functions, while the DAT availability of the posterior putamen was not. However, the baseline DAT availability of the striatal sub-regions did not influence the cognitive decline or cognitive status in the longitudinal cognitive assessment. ConclusionOur results suggest that striatal DAT availability may determine MCI in patients with de novo PD. Dopamine loss in the associative and limbic striatum is closely linked to cognitive deficits in early-stage PD, although it does not affect cognitive prognosis.

The Strength Model of Self-Regulation: Conclusions From the Second Decade of Willpower Research

The strength model of self-regulation uses a muscle analogy to explain patterns of ego depletion, conservation of willpower, and improved performance after frequent exercise. Our 2007 overview of the literature has been well cited, presumably because of the phenomenon’s importance to theories of selfhood and a wide assortment of applied contexts, including problem behaviors. Some researchers have put forward rival theoretical accounts, and others have questioned the existence of the phenomenon. The weight of evidence continues to support the usefulness of the strength model, albeit amid continuing updates and revisions.

Identification of Galeterone and Abiraterone as Inhibitors of Dehydroepiandrosterone Sulfonation Catalyzed by Human Hepatic Cytosol, SULT2A1, SULT2B1b, and SULT1E1

Galeterone and abiraterone acetate are antiandrogens developed for the treatment of metastatic castration-resistant prostate cancer. In the present study, we investigated the effect of these drugs on dehydroepiandrosterone (DHEA) sulfonation catalyzed by human liver and intestinal cytosols and human recombinant sulfotransferase enzymes (SULT2A1, SULT2B1b, and SULT2E1) and compared their effects to those of other antiandrogens (cyproterone acetate, spironolactone, and danazol). Each of these chemicals (10 μM) inhibited DHEA sulfonation catalyzed by human liver and intestinal cytosols. Enzyme kinetic analysis showed that galeterone and abiraterone acetate inhibited human liver cytosolic DHEA sulfonation with apparent Ki values at submicromolar concentrations, whereas cyproterone acetate, spironolactone, and danazol inhibited it with apparent Ki values at low micromolar concentrations. The temporal pattern of abiraterone formation and abiraterone acetate depletion suggested that the metabolite abiraterone, not the parent drug abiraterone acetate, was responsible for the inhibition of DHEA sulfonation in incubations containing human liver cytosol and abiraterone acetate. Consistent with this proposal, similar apparent Ki values were obtained, regardless of whether abiraterone or abiraterone acetate was added to the enzymatic incubation. Abiraterone was more effective than abiraterone acetate in inhibiting DHEA sulfonation when catalyzed by human recombinant SULT2A1 or SULT2B1b. In conclusion, galeterone and abiraterone are novel inhibitors of DHEA sulfonation, as determined in enzymatic incubations containing human tissue cytosol (liver or intestinal) or human recombinant SULT enzyme (SULT2A1, SULT2B1b, or SULT1E1). Our findings on galeterone and abiraterone may have implications in drug-drug interactions and biosynthesis of steroid hormones.