A chromosome-level Populus qiongdaoensis genome assembly provides insights into tropical adaptation and a cryptic turnover of sex determination.

Populus species have long been used as model organisms to study the adaptability of trees and the evolution of sex chromosomes. As a species belonging to the section Populus and limited to tropical areas, the P. qiongdaoensis genome contains important information for tropical poplar studies and protection. Here, we report a chromosome-level genome assembly and annotation of a female P. qiongdaoensis. Gene family clustering, positive selection detection and historical reconstruction of population dynamics revealed the tropical adaptation of P. qiongdaoensis, and showed convergent evolution with another tropical poplar, P. ilicifolia, at the molecular level, especially on some functional genes (e.g., PIF3 and PIL1). In addition, we also identified a ZW sex determination system on chromosome 19 of P. qiongdaoensis, and inferred that it seems to have a similar sex determination mechanism to other poplars, controlled by a type-A cytokinin response regulator (RR) gene. However, comparison and phylogenetic analysis of the sex determination regions confirmed a cryptic sex turnover event in the section Populus, which may be caused by the translocation and duplication of the RR gene driven by Helitron-like transposable elements. Our study provides new insights into the environmental adaptation and sex chromosome evolution of poplars, and emphasizes the importance of using long read sequencing in ecological and evolutionary inferences of plants.

Repeated turnovers keep sex chromosomes young in willows.

BACKGROUND: Salicaceae species have diverse sex determination systems and frequent sex chromosome turnovers. However, compared with poplars, the diversity of sex determination in willows is poorly understood, and little is known about the evolutionary forces driving their turnover. Here, we characterized the sex determination in two Salix species, S. chaenomeloides and S. arbutifolia, which have an XY system on chromosome 7 and 15, respectively. RESULTS: Based on the assemblies of their sex determination regions, we found that the sex determination mechanism of willows may have underlying similarities with poplars, both involving intact and/or partial homologs of a type A cytokinin response regulator (RR) gene. Comparative analyses suggested that at least two sex turnover events have occurred in Salix, one preserving the ancestral pattern of male heterogamety, and the other changing heterogametic sex from XY to ZW, which could be partly explained by the "deleterious mutation load" and "sexually antagonistic selection" theoretical models. We hypothesize that these repeated turnovers keep sex chromosomes of willow species in a perpetually young state, leading to limited degeneration. CONCLUSIONS: Our findings further improve the evolutionary trajectory of sex chromosomes in Salicaceae species, explore the evolutionary forces driving the repeated turnovers of their sex chromosomes, and provide a valuable reference for the study of sex chromosomes in other species.

Histone Lysine Methylation Modification and Its Role in Vascular Calcification.

Histone methylation is an epigenetic change mediated by histone methyltransferase, and has been connected to the beginning and progression of several diseases. The most common ailments that affect the elderly are cardiovascular and cerebrovascular disorders. They are the leading causes of death, and their incidence is linked to vascular calcification (VC). The key mechanism of VC is the transformation of vascular smooth muscle cells (VSMCs) into osteoblast-like phenotypes, which is a highly adjustable process involving a variety of complex pathophysiological processes, such as metabolic abnormalities, apoptosis, oxidative stress and signalling pathways. Many researchers have investigated the mechanism of VC and related targets for the prevention and treatment of cardiovascular and cerebrovascular diseases. Their findings revealed that histone lysine methylation modification may play a key role in the various stages of VC. As a result, a thorough examination of the role and mechanism of lysine methylation modification in physiological and pathological states is critical, not only for identifying specific molecular markers of VC and new therapeutic targets, but also for directing the development of new related drugs. Finally, we provide this review to discover the association between histone methylation modification and VC, as well as diverse approaches with which to investigate the pathophysiology of VC and prospective treatment possibilities.

The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification.

Arterial calcification is highly prevalent, particularly in patients with end-stage renal disease (ESRD). The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is the critical process for the development of arterial calcification. However, the detailed mechanism of VSMCs calcification remains to be elucidated. Here, we investigated the role of exosomes (Exos) derived from endothelial cells (ECs) in arterial calcification and its potential mechanisms in ESRD. Accelerated VSMCs calcification was observed when VSMCs were exposed to ECs culture media stimulated by uremic serum or high concentration of inorganic phosphate (3.5 mM Pi). and the pro-calcification effect of the ECs culture media was attenuated by exosome depletion. Exosomes derived from high concentrations of inorganic phosphate-induced ECs (ECsHPi-Exos) could be uptaken by VSMCs and promoted VSMCs calcification. Microarray analysis showed that miR-670-3p was dramatically increased in ECsHPi-Exos compared with exosomes derived from normal concentrations of inorganic phosphate (0.9 mM Pi) induced ECs (ECsNPi-Exos). Mechanistically, insulin-like growth factor 1 (IGF-1) was identified as the downstream target of miR-670-3p in regulating VSMCs calcification. Notably, ECs-specific knock-in of miR-670-3p of the 5/6 nephrectomy with a high-phosphate diet (miR-670-3pEC-KI + NTP) mice that upregulated the level of miR-670-3p in artery tissues and significantly increased artery calcification. Finally, we validated that the level of circulation of plasma exosomal miR-670-3p was much higher in patients with ESRD compared with healthy controls. Elevated levels of plasma exosomal miR-670-3p were associated with a decline in IGF-1 and more severe artery calcification in patients with ESRD. Collectively, these findings suggested that ECs-derived exosomal miR-670-3p could promote arterial calcification by targeting IGF-1, which may serve as a potential therapeutic target for arterial calcification in ESRD patients.

Cellular Crosstalk in the Vascular Wall Microenvironment: The Role of Exosomes in Vascular Calcification.

Vascular calcification is prevalent in aging, diabetes, chronic kidney disease, cardiovascular disease, and certain genetic disorders. However, the pathogenesis of vascular calcification is not well-understood. It has been progressively recognized that vascular calcification depends on the bidirectional interactions between vascular cells and their microenvironment. Exosomes are an essential bridge to mediate crosstalk between cells and organisms, and thus they have attracted increased research attention in recent years. Accumulating evidence has indicated that exosomes play an important role in cardiovascular disease, especially in vascular calcification. In this review, we introduce vascular biology and focus on the crosstalk between the different vessel layers and how their interplay controls the process of vascular calcification.

Pervasive hybridization during evolutionary radiation of Rhododendron subgenus Hymenanthes in mountains of southwest China.

Radiations are especially important for generating species biodiversity in mountainous ecosystems. The contribution of hybridization to such radiations has rarely been examined. Here, we use extensive genomic data to test whether hybridization was involved in evolutionary radiation within Rhododendron subgenus Hymenanthes, whose members show strong geographic isolation in the mountains of southwest China. We sequenced genomes for 143 species of this subgenus and 93 species of four other subgenera, and found that Hymenanthes was monophyletic and radiated during the late Oligocene to middle Miocene. Widespread hybridization events were inferred within and between the identified clades and subclades. This suggests that hybridization occurred both early and late during diversification of subgenus Hymenanthes, although the extent to which hybridization, speciation through mixing-isolation-mixing or hybrid speciation, accelerated the diversification needs further exploration. Cycles of isolation and contact in such and other montane ecosystems may have together promoted species radiation through hybridization between diverging populations and species. Similar radiation processes may apply to other montane floras in this region and elsewhere.

Designing Multifunctional Co and Fe Co-Doped MoS2 Nanocube Electrodes for Dye-Sensitized Solar Cells, Perovskite Solar Cells, and a Supercapacitor.

In the present study, three types of specific solid, core-shell, and hollow structured cobalt and iron co-doped MoS2 nanocubes (denoted as s-Co-Fe-MoS x , c-Co-Fe-MoS x , and h-Co-Fe-MoS x ) are controllably synthesized for the first time by regulating the reactant mass ratios. The prepared Co-Fe-MoS x nanocubes can function as a counter electrode in dye-sensitized and perovskite solar cells (DSCs and PSCs) and a working electrode in a supercapacitor. In the DSC system, the c-Co-Fe-MoS x nanocubes exhibit the maximum catalytic activity to the Co3+/2+ redox couple regeneration, and the device achieves a power conversion efficiency (PCE) of 8.69%, significantly higher than the devices using s-Co-Fe-MoS x (6.61%) and h-Co-Fe-MoS x (7.63%) counter electrodes. Similarly, all of the prepared Co-Fe-MoS x nanocubes show decent activity in PSCs and the device using the c-Co-Fe-MoS x counter electrode achieves the highest PCE of 6.88%. It is worth noting that, as the supercapacitor working electrode, the h-Co-Fe-MoS x exhibits a specific capacitance of 85.4 F g-1, significantly higher than the parallel values achieved by the s-Co-Fe-MoS x and c-Co-Fe-MoS x electrodes under identical conditions.

The Controversial Role of Irisin in Clinical Management of Coronary Heart Disease.

Irisin, a PGC1α-dependent myokine, was once believed to have beneficial effects induced by exercise. Since its first discovery of adipose browning in 2012, multiple studies have been trying to explore the metabolic functions of irisin, such as glucose and lipid metabolism. However, recently many studies with irisin concentration measuring were doubt for methodological problems, which may account for the continuous inconsistencies. New tools like recombinant irisin and gene-knockout mice are required to reconfirm the questioned functions of irisin. In this paper, we make a critical introduction to the latest researches concerning the relationship between irisin and coronary heart disease, which includes atherosclerosis, stable angina pectoris and acute coronary syndromes. These studies provided various controversial evidence of short and long-term monitoring and therapeutic effect from molecular cellular mechanisms, in vivo experiments and epidemiological investigation. But with ambiguities, irisin still has a long way to go to identify its functions in the clinical management.

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Ferroptosis is classified as an iron-dependent form of regulated cell death (RCD) attributed to the accumulation of lipid hydroperoxides and redox imbalance. In recent years, accumulating researches have suggested that ferroptosis may play a vital role in the development of diverse metabolic diseases, for example, diabetes and its complications (e.g., diabetic nephropathy, diabetic cardiomyopathy, diabetic myocardial ischemia/reperfusion injury and atherosclerosis [AS]), metabolic bone disease and adrenal injury. However, the specific physiopathological mechanism and precise therapeutic effect is still not clear. In this review, we summarized recent advances about the development of ferroptosis, focused on its potential character as the therapeutic target in metabolic diseases, and put forward our insights on this topic, largely to offer some help to forecast further directions.

An Overview of ICA/BSS-Based Application to Alzheimer's Brain Signal Processing.

Alzheimer's disease (AD) is by far the most common cause of dementia associated with aging. Early and accurate diagnosis of AD and ability to track progression of the disease is increasingly important as potential disease-modifying therapies move through clinical trials. With the advent of biomedical techniques, such as computerized tomography (CT), electroencephalography (EEG), magnetoencephalography (MEG), positron emission tomography (PET), magnetic resonance imaging (MRI), and functional magnetic resonance imaging (fMRI), large amounts of data from Alzheimer's patients have been acquired and processed from which AD-related information or "signals" can be assessed for AD diagnosis. It remains unknown how best to mine complex information from these brain signals to aid in early diagnosis of AD. An increasingly popular technique for processing brain signals is independent component analysis or blind source separation (ICA/BSS) that separates blindly observed signals into original signals that are as independent as possible. This overview focuses on ICA/BSS-based applications to AD brain signal processing.

A General Model to Explain Repeated Turnovers of Sex Determination in the Salicaceae.

Dioecy, the presence of separate sexes on distinct individuals, has evolved repeatedly in multiple plant lineages. However, the specific mechanisms by which sex systems evolve and their commonalities among plant species remain poorly understood. With both XY and ZW sex systems, the family Salicaceae provides a system to uncover the evolutionary forces driving sex chromosome turnovers. In this study, we performed a genome-wide association study to characterize sex determination in two Populus species, P. euphratica and P. alba. Our results reveal an XY system of sex determination on chromosome 14 of P. euphratica, and a ZW system on chromosome 19 of P. alba. We further assembled the corresponding sex-determination regions, and found that their sex chromosome turnovers may be driven by the repeated translocations of a Helitron-like transposon. During the translocation, this factor may have captured partial or intact sequences that are orthologous to a type-A cytokinin response regulator gene. Based on results from this and other recently published studies, we hypothesize that this gene may act as a master regulator of sex determination for the entire family. We propose a general model to explain how the XY and ZW sex systems in this family can be determined by the same RR gene. Our study provides new insights into the diversification of incipient sex chromosomes in flowering plants by showing how transposition and rearrangement of a single gene can control sex in both XY and ZW systems.

Survival in the Tropics despite isolation, inbreeding and asexual reproduction: insights from the genome of the world's southernmost poplar (Populus ilicifolia).

Species are becoming extinct at unprecedented rates as a consequence of human activity. Hence it is important to understand the evolutionary dynamics of species with already small population sizes. Populus ilicifolia is a vulnerable poplar species that is isolated from other poplar species and is uniquely adapted to the Tropics. It has a very limited size, reproduces partly clonally and is therefore an excellent case study for conservation genomics. We present here the first annotated draft genome of P. ilicifolia, characterize genome-wide patterns of polymorphisms and compare those to other poplar species with larger natural ranges. P. ilicifolia experienced a more prolonged and severe decline of effective population size (Ne ) and signs of genetic erosion than any other poplar species with which it was compared. At present, the species has the lowest genome-wide genetic diversity, the highest abundance of long runs of homozygosity, high inbreeding levels as well as a high overall accumulation of deleterious variants. However, more effective purging of severely deleterious variants and adaptation to the Tropics may have contributed to its survival. Hence, in spite of its limited genetic variation, it is certainly worth pursuing the conservation efforts of this unique species.

Analysis of Alternative Splicing and Alternative Polyadenylation in Populus alba var. pyramidalis by Single-Molecular Long-Read Sequencing.

Poplars are worldwidely cultivated with ecologically and economically important value. Populus alba var. pyramidalis (= P. bolleana) is a main tree of the farmland shelter-belt system in the arid region of Northwest China due to its rapid growth, erect stems, and high biomass production. However, the full-length messenger RNA (mRNA) sequences and complete structure of P. alba var. pyramidalis remain unclear. In this study, using single-molecular real-time (SMRT) and next-generation high-throughput sequencing (NGS) platform, we sequenced transcripts from leaf, root, xylem, and phloem of P. alba var. pyramidalis, to obtain the full-length mRNA transcripts and annotate the complete structure. In total, 86,327 mapped full-length non-chimeric (FLNC) reads were identified, with 705 previously unannotated loci and 3,410 long noncoding RNAs (lncRNAs) and 174 fusion genes found. Alternative spicing (AS) events were detected in 7,536 genes, of which 4,652 genes had multiple AS events. A total of 10,213 alternative polyadenylation (APA) sites were identified, with two or more APA sites observed in 2,212 genes. Our transcriptome data provided the full-length sequences and gene isoforms of transcripts for P. alba var. pyramidalis, which will be helpful in improving our understanding for the genome annotation and gene structures of P. alba var. pyramidalis.

The draft genome sequence of a desert tree Populus pruinosa.

Populus pruinosa is a large tree that grows in deserts and shows distinct differences in both morphology and adaptation compared to its sister species, P. euphratica. Here we present a draft genome sequence for P. pruinosa and examine genomic variations between the 2 species. A total of 60 Gb of clean reads from whole-genome sequencing of a P. pruinosa individual were generated using the Illumina HiSeq2000 platform. The assembled genome is 479.3 Mb in length, with an N50 contig size of 14.0 kb and a scaffold size of 698.5 kb; 45.47% of the genome is composed of repetitive elements. We predicted 35 131 protein-coding genes, of which 88.06% were functionally annotated. Gene family clustering revealed 224 unique and 640 expanded gene families in the P. pruinosa genome. Further evolutionary analysis identified numerous genes with elevated values for pairwise genetic differentiation between P. pruinosa and P. euphratica. We provide the genome sequence and gene annotation for P. pruinosa. A large number of genetic variations were recovered by comparison of the genomes between P. pruinosa and P. euphratica. These variations will provide a valuable resource for studying the genetic bases for the phenotypic and adaptive divergence of the 2 sister species.

Classification of MRI and psychological testing data based on support vector machine.

Alzheimer's disease (AD) is a progressive, and often fatal, brain disease that causes neurodegeneration, resulting in memory loss as well as other cognitive and behavioral problems. Here, we propose a novel multimodal method combining independent components from MRI measures and clinical assessments to distinguish Alzheimer's patients or mild cognitive impairment (MCI) subjects from healthy elderly controls. 70 AD subjects (mean age: 77.15 ± 6.2 years), 98 MCI subjects (mean age: 76.91 ± 5.7 years), and 150 HC subjects (mean age: 75.69 ± 3.8 years) were analyzed. Our method includes the following steps: pre-processing, estimating the number of independent components from the MR image data, extracting effective voxels for classification, and classification using a support vector machine (SVM)-based classifier. As a result, with regards to classifying AD from healthy controls, we achieved a classification accuracy of 97.7%, sensitivity of 99.2%, and specificity of 96.7%; for differentiating MCI from healthy controls, we achieved a classification accuracy of 87.8%, a sensitivity of 86.0%, and a specificity of 89.6; these results are better than those obtained with clinical measurements alone (accuracy of 79.5%, sensitivity of 74.0%, and specificity of 85.1%). We found that (1) both AD patients and MCI subjects showed brain tissue loss, but the volumes of gray matter loss in MCI subjects was far less, supporting the notion that MCI is a prodromal stage of AD; and (2) combining gray matter features from MRI and three commonly used measures of mental status, cognitive function improved classification accuracy, sensitivity, and specificity compared with classification using only independent components or clinical measurements.

[Bi-modality image classification based on independent component analysis].

We in the present research proposed a classification method that applied infomax independent component analysis (ICA) to respectively extract single modality features of structural magnetic resonance imaging (sMRI) and positron emission tomography (PET). And then we combined these two features by using a method of weight combination. We found that the present method was able to improve the accurate diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Compared AD to healthy controls (HC): the study achieved a classification accuracy of 93.75%, with a sensitivity of 100% and a specificity of 87.64%. Compared MCI to HC: classification accuracy was 89.35%, with a sensitivity of 81.85% and a specificity of 99.36%. The experimental results showed that the bi-modality method performed better than the individual modality in comparison to classification accuracy.

[Research on a successively increasing feature selection algorithm of EEG signal for driving fatigue based on SVM].

Electroencephalogram (EEG) signals provide an objective physiological index for the identification of the driver's fatigue state. It is very important to choose appropriate channels and EEG signal features adaptively due to the features varying with different subjects and time. A support vector machine (SVM) based increasing feature selection algorithm for driving fatigue EEG classification is presented in this paper. The algorithm is a method to select EEG channels and features for driving fatigue adaptively in an ascending order. We can select the optimal feature each time from the remaining candidate features using the optimized SVM model minimum error rate as the index. The experimental calculation has characteristics of using 16 electrode channels which cover the whole head in the main area, of selecting 208 candidate features as the initial set, of selecting to the EEG data calculation recorded in 5 different time periods of a subject, and of choosing error rate of 2% as the algorithm termination condition. The selected features and models, therefore, can reach a high level of classification and generalization ability.

An MRI study of symptomatic adhesive capsulitis.

BACKGROUND: Appilication of MR imaging to diagnose Adhesive Capsulitis (AC) has previously been described. However, there is insufficient information available for the MRI analysis of AC. This study is to describe and evaluate the pathomorphology of the shoulder in Asian patients with AC compared to healthy volunteers. METHODOLOGY/PRINCIPAL FINDINGS: 60 Asian patients with clinically diagnosed AC and 60 healthy volunteers without frozen shoulder underwent MRI of the shoulder joint. All subjects who were age- and sex-matched control ones underwent routine MRI scans of the affected shoulder, including axial, oblique coronal, oblique sagittal T1WI SE and coronal oblique T2WI FSE sequences. Significant abnormal findings were observed on MRI, especially at the rotator cuff interval. The coracohumeral ligament (CHL), articular capsule thickness in the rotator cuff interval as well as the fat space under coracoid process were evaluated. MRI showed that patients with adhesive capsulitis had a significantly thickened coracohumeral ligament and articular capsule in the rotator cuff interval compared to the control subjects (4.2 vs. 2.4 mm, 7.2 vs. 4.4 mm; p<0.05). Partial or complete obliteration of the subcoracoid fat triangle was significantly more frequent in patients with adhesive capsulitis compared with control subjects (73% vs. 13%, 26% vs. 1.6%; p<0.001). Synovitis-like abnormality around the long biceps tendon was significantly more common in patients with adhesive capsulitis than in control subjects. With regards to the inter-observer variability, two MR radiologists had an excellent kappa value of 0.86. CONCLUSIONS/SIGNIFICANCE: MRI can be used to show characteristic findings in diagnosing AC. Thickening of the CHL and the capsule at the rotator cuff interval and complete obliteration of the fat triangle under the coracoid process have been shown to be the most characteristic MR findings seen with AC.

Independent component analysis-based classification of Alzheimer's disease MRI data.

There is an unmet medical need to identify neuroimaging biomarkers that allow us to accurately diagnose and monitor Alzheimer's disease (AD) at its very early stages and to assess the response to AD-modifying therapies. To a certain extent, volumetric and functional magnetic resonance imaging (fMRI) studies can detect changes in structure, cerebral blood flow, and blood oxygenation that distinguish AD and mild cognitive impairment (MCI) subjects from healthy control (HC) subjects. However, it has been challenging to use fully automated MRI analytic methods to identify potential AD neuroimaging biomarkers. We have thus proposed a method based on independent component analysis (ICA) for studying potential AD-related MR image features that can be coupled with the use of support vector machine (SVM) for classifying scans into categories of AD, MCI, and HC subjects. The MRI data were selected from the Open Access Series of Imaging Studies (OASIS) and the Alzheimer's Disease Neuroimaging Initiative databases. The experimental results showed that the ICA method coupled with SVM classifier can differentiate AD and MCI patients from HC subjects, although further methodological improvement in the analytic method and inclusion of additional variables may be required for optimal classification.

The role of T cells in osteoporosis, an update.

Emerging evidence highlights the importance of the interplay between the bone and immune systems. That evidence bolsters a longstanding recognition that estrogen deficiency, infection, inflammation, and autoimmune disorders are associated with systemic and local bone loss. Yet, only recently has an understanding emerged that T lymphocytes and their products act as key regulators of osteoclast formation, life span, and activity. This review presents this understanding of the process of T lymphocytes and their products mediating osteoporosis and explores some of the most recent findings and hypotheses to explain their action in bone. A more complete appreciation of the interactions between immune and bone cells should lead to targeted therapeutic strategies for diseases that affect either or both systems.