Uptake, sequestration and tolerance of cadmium at cellular levels in the hyperaccumulator plant species Sedum alfredii.

Sedum alfredii is one of a few plant species known to hyperaccumulate cadmium (Cd). Uptake, localization, and tolerance of Cd at cellular levels in shoots were compared in hyperaccumulating (HE) and non-hyperaccumulating (NHE) ecotypes of Sedum alfredii. X-ray fluorescence images of Cd in stems and leaves showed only a slight Cd signal restricted within vascular bundles in the NHEs, while enhanced localization of Cd, with significant tissue- and age-dependent variations, was detected in HEs. In contrast to the vascular-enriched Cd in young stems, parenchyma cells in leaf mesophyll, stem pith and cortex tissues served as terminal storage sites for Cd sequestration in HEs. Kinetics of Cd transport into individual leaf protoplasts of the two ecotypes showed little difference in Cd accumulation. However, far more efficient storage of Cd in vacuoles was apparent in HEs. Subsequent analysis of cell viability and hydrogen peroxide levels suggested that HE protoplasts exhibited higher resistance to Cd than those of NHE protoplasts. These results suggest that efficient sequestration into vacuoles, as opposed to rapid transport into parenchyma cells, is a pivotal process in Cd accumulation and homeostasis in shoots of HE S. alfredii. This is in addition to its efficient root-to-shoot translocation of Cd

A Distance Transformation Deep Forest Framework With Hybrid-Feature Fusion for CXR Image Classification

Detecting pneumonia, especially coronavirus disease 2019 (COVID-19), from chest X-ray (CXR) images is one of the most effective ways for disease diagnosis and patient triage. The application of deep neural networks (DNNs) for CXR image classification is limited due to the small sample size of the well-curated data. To tackle this problem, this article proposes a distance transformation-based deep forest framework with hybrid-feature fusion (DTDF-HFF) for accurate CXR image classification. In our proposed method, hybrid features of CXR images are extracted in two ways: hand-crafted feature extraction and multigrained scanning. Different types of features are fed into different classifiers in the same layer of the deep forest (DF), and the prediction vector obtained at each layer is transformed to form distance vector based on a self-adaptive scheme. The distance vectors obtained by different classifiers are fused and concatenated with the original features, then input into the corresponding classifier at the next layer. The cascade grows until DTDF-HFF can no longer gain benefits from the new layer. We compare the proposed method with other methods on the public CXR datasets, and the experimental results show that the proposed method can achieve state-of-the art (SOTA) performance. The code will be made publicly available at https://github.com/hongqq/DTDF-HFF

Sugar Metabolism Regulates Flavor Preferences and Portal Glucose Sensing

In most species, including humans, food preference is primarily controlled by nutrient value. In particular, glucose-containing sugars exert exquisitely strong effects on food choice via gut-generated signals. However, the identity of the visceral signals underlying glucose’s rewarding effects remains uncertain. In particular, it is unknown whether sugar metabolism mediates the formation of preferences for glucose-containing sugars. Using the mouse as a model organism, we made use of a combination of conditioning schedules, gastrointestinal nutrient administration, and chromatographic/electrochemical methods to assess the behavioral and neural effects of activating the gut with either metabolizable glucose or a non-metabolizable glucose analog. We show that mice display much superior preferences for flavors associated with intra-gastric infusions of glucose compared to flavors associated with intra-gastric infusions of the non-metabolizable glucose analog α-methyl-D-glucopyranoside (“MDG,” an activator of intestinal sodium/glucose co-transporters). These effects were unaffected by surgical bypassing of the duodenum, suggesting glucose-specific post-absorptive sensing mechanisms. Consistently, intra-portal infusions of glucose, but not of MDG, induced significant rises in dopamine (DA) levels within brain reward circuits. Our data reveal that the unmatched rewarding effects of glucose-containing sugars cannot be accounted for by metabolism-independent activation of sodium/glucose cotransporters; rather, they point to glucose metabolism as the physiological mechanism underlying the potent reward value of sugar-sweetened flavored beverages. In particular, no circulating “gut factors” need to be invoked to explain the reward value of ingested glucose. Thus, instead of circulating gut hormones, portal-mesenteric sensing of glucose emerges as the preferential physiological pathway for sugar reward

Five New Amicoumacins Isolated from a Marine-Derived Bacterium Bacillus subtilis

Four novel amicoumacins, namely lipoamicoumacins A–D (1–4), and one new bacilosarcin analog (5) were isolated from culture broth of a marine-derived bacterium Bacillus subtilis, together with six known amicoumacins. Their structures were elucidated on the basis of extensive spectroscopic (2D NNR, IR, CD and MS) analysis and in comparison with data in literature

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted 'blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted ‘blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article

Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

Funder: Shanghai Municipal Commission of Health and Family Planning Shanghai Shenkang Hospital Development Center Shanghai Municipal Education Commission National Natural Science Foundation of China Shanghai Committee of Science and Technology Xinhua Hospital of Shanghai Jiao Tong University School of Medicine Guangdong Key Project in "Development of new tools for diagnosis and treatment of Autism "Funder: Shanghai Municipal Commission of Health and Family Planning Shanghai Municipal Education Commission National Natural Science Foundation of China the National Key Research and Development Program of China ZJ LabFunder: National Human Genetic Resources Sharing Service Platform 111 Project ZJ LabFunder: National Natural Science Foundation of China ZJ LabAbstract: Bumetanide has been reported to alter synaptic excitation–inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up. Side effects were monitored throughout the treatment course. Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score ≥ 3. The improvement in clinical symptoms was confirmed by CGI. GABA/Glx ratio in both the IC and VC decreased more rapidly over the 3-month period in the bumetanide group than that in the control group. This decrease in the IC was associated with the symptom improvement in the bumetanide group. Our study confirmed the clinical efficacy of bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glx ratios. This study suggests that the GABA/Glx ratio measured by MRS may provide a neuroimaging biomarker for assessing treatment efficacy for bumetanide

Changes in microstates of first-episode untreated nonsuicidal self-injury adolescents exposed to negative emotional stimuli and after receiving rTMS intervention

BackgroundNonsuicidal self-injury (NSSI) is a common mental health threat in adolescents, peaking in adolescence with a lifetime prevalence of ~17%–60%, making it a high-risk risk factor for suicide. In this study, we compared changes in microstate parameters in depressed adolescents with NSSI, depressed adolescents, and healthy adolescents during exposure to negative emotional stimuli, and further explored the improvement of clinical symptoms and the effect of microstate parameters of repetitive transcranial magnetic stimulation (rTMS) in depressed adolescents with NSSI, and more evidence was provided for potential mechanisms and treatment optimization for the occurrence of NSSI behaviors in adolescents.MethodsSixty-six patients with major depressive disorder (MDD) exhibiting NSSI behavior (MDD + NSSI group), 52 patients with MDD (MDD group), and 20 healthy subjects (HC group) were recruited to perform neutral and negative emotional stimulation task. The age range of all subjects was 12–17 years. All participants completed the Hamilton Depression Scale, the Patient Health Questionnaire-9, the Ottawa Self-Injury Scale and a self-administered questionnaire to collect demographic information. We provided two different treatments to 66 MDD adolescents with NSSI; 31 patients received medication and completed post-treatment scale assessments and EEG acquisitions, and 21 patients received medication combined with rTMS and completed post-treatment scale assessments and EEG acquisitions. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline, using the EEGLAB toolbox in MATLAB. Use the Microstate Analysis Toolbox in EEGLAB for segmentation and computation of microstates, and calculate a topographic map of the microstate segmentation of the EEG signal for a single subject in each dataset, and four parameters were obtained for each microstate classification: global explained variance (GEV), mean duration (Duration), average number of occurrences per second (Occurrence), and average percentage of total analysis time occupied (Coverage), which were then statistically analyzed.ResultsOur results indicate that MDD adolescents with NSSI exhibit abnormalities in MS 3, MS 4, and MS 6 parameters when exposed to negative emotional stimuli compared to MDD adolescents and healthy adolescents. The results also showed that medication combined with rTMS treatment improved depressive symptoms and NSSI performance more significantly in MDD adolescents with NSSI compared to medication treatment, and affected MS 1, MS 2, and MS 4 parameters in MDD adolescents with NSSI, providing microstate evidence for the moderating effect of rTMS.ConclusionMDD adolescents with NSSI showed abnormal changes in several microstate parameters when receiving negative emotional stimuli, and compared to those not receiving rTMS treatment, MDD adolescents with NSSI treated with rTMS showed more significant improvements in depressive symptoms and NSSI performance, as well as improvements in EEG microstate abnormalities

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family