Molecular basis for potent B cell responses to antigen displayed on particles of viral size.

Multivalent viral epitopes induce rapid, robust and T cell-independent humoral immune responses, but the biochemical basis for such potency remains incompletely understood. We take advantage of a set of liposomes of viral size engineered to display affinity mutants of the model antigen (Ag) hen egg lysozyme. Particulate Ag induces potent 'all-or-none' B cell responses that are density dependent but affinity independent. Unlike soluble Ag, particulate Ag induces signal amplification downstream of the B cell receptor by selectively evading LYN-dependent inhibitory pathways and maximally activates NF-κB in a manner that mimics T cell help. Such signaling induces MYC expression and enables even low doses of particulate Ag to trigger robust B cell proliferation in vivo in the absence of adjuvant. We uncover a molecular basis for highly sensitive B cell responses to viral Ag display that is independent of encapsulated nucleic acids and is not merely accounted for by avidity and B cell receptor cross-linking.

ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.

High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.

Ethylene enhances MdMAPK3-mediated phosphorylation of MdNAC72 to promote apple fruit softening.

The phytohormone ethylene plays an important role in promoting the softening of climacteric fruits, such as apples (Malus domestica); however, important aspects of the underlying regulatory mechanisms are not well understood. In this study, we identified apple MITOGEN-ACTIVATED PROTEIN KINASE 3 (MdMAPK3) as an important positive regulator of ethylene-induced apple fruit softening during storage. Specifically, we show that MdMAPK3 interacts with and phosphorylates the transcription factor NAM-ATAF1/2-CUC2 72 (MdNAC72), which functions as a transcriptional repressor of the cell wall degradation-related gene POLYGALACTURONASE1 (MdPG1). The increase in MdMAPK3 kinase activity was induced by ethylene, which promoted the phosphorylation of MdNAC72 by MdMAPK3. Additionally, MdPUB24 functions as an E3 ubiquitin ligase to ubiquitinate MdNAC72, resulting in its degradation via the 26S proteasome pathway, which was enhanced by ethylene-induced phosphorylation of MdNAC72 by MdMAPK3. The degradation of MdNAC72 increased the expression of MdPG1, which in turn promoted apple fruit softening. Notably, using variants of MdNAC72 that were mutated at specific phosphorylation sites, we observed that the phosphorylation state of MdNAC72 affected apple fruit softening during storage. This study thus reveals that the ethylene-MdMAPK3-MdNAC72-MdPUB24 module is involved in ethylene-induced apple fruit softening, providing insights into climacteric fruit softening.

ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression.

Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, understanding the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investigated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-κB) and Activator protein 1 (AP1) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4 promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.

ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation.

High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high-risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8-10% of primary NB patients are ALK-positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the "2p-gain" region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v-sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI-sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p-gain, may benefit from ALK TKI-based therapeutic intervention.

ProBDNF contributed to patrolling monocyte infiltration and renal damage in systemic lupus erythematosus.

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1+ patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1+ PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE.

Role of TFEB-autophagy lysosomal pathway in palmitic acid induced renal tubular epithelial cell injury.

Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury.

Phosphorylation of MdCYTOKININ RESPONSE FACTOR4 suppresses ethylene biosynthesis during apple fruit ripening.

The plant hormone ethylene plays a central role in the ripening of climacteric fruits, such as apple (Malus domestica). Ethylene biosynthesis in apple fruit can be suppressed by calcium ions (Ca2+); however, the underlying mechanism is largely unknown. In this study, we identified an apple APETALA2/ETHYLENE-RESPONSIVE FACTOR (AP2/ERF) transcription factor, MdCYTOKININ RESPONSE FACTOR4 (MdCRF4), which functions as a transcriptional activator of ethylene biosynthesis- and signaling-related genes, including Md1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID SYNTHASE1 (MdACS1) and MdETHYLENE-RESPONSIVE FACTOR3 (MdERF3), as a partner of the calcium sensor, calmodulin. Ca2+ promoted the Ca2+/CaM2-mediated phosphorylation of MdCRF4, resulting in MdCRF4 recognition by the E3 ubiquitin ligase MdXB3 ORTHOLOG 1 IN ARABIDOPSIS THALIANA (MdXBAT31), and consequently its ubiquitination and degradation via the 26S proteasome pathway. This in turn resulted in lower expression of MdACS1 and MdERF3 and reduced ethylene biosynthesis. Transiently overexpressing various MdCRF4 proteins with specific mutated phosphorylation sites revealed that the phosphorylation state of MdCRF4 affects the ripening of apple fruit. The results reveal that a Ca2+/CaM-MdCRF4-MdXBAT31 module is involved in Ca2+-suppressed ethylene biosynthesis, which delays apple fruit ripening. This provides insights into fruit ripening that may result in strategies for extending fruit shelf life.

Exogenous Ca2+ promotes transcription factor phosphorylation to suppress ethylene biosynthesis in apple.

Ethylene biosynthesis in apple (Malus domestica) fruit can be suppressed by calcium ions (Ca2+) during storage; however, the underlying mechanisms are unclear. In this study, we identified the apple transcription factor MCM1-AGAMOUS-DEFICIENS-SRF5 (MdMADS5), which functions as a transcriptional activator of the ethylene biosynthesis-related gene 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID SYNTHASE1 (MdACS1), a partner of the calcium sensor CALCIUM-DEPENDENT PROTEIN KINASES7 (MdCDPK7). Ca2+ promoted the MdCDPK7-mediated phosphorylation of MdMADS5, which resulted in the degradation of MdMADS5 via the 26S proteasome pathway. MdCDPK7 also phosphorylated 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID OXIDASE1 (MdACO1), the key enzyme in ethylene biosynthesis, leading to MdACO1 degradation and inhibition of ethylene biosynthesis. Our results reveal that Ca2+/MdCDPK7-MdMADS5 and Ca2+/MdCDPK7-MdACO1 are involved in Ca2+-suppressed ethylene biosynthesis, which delays apple fruit ripening. These findings provide insights into fruit ripening, which may lead to the development of strategies for extending the shelf life of fruit.

Hydrophobically Associated Hydrogel for High Sensitivity and Resolution of an Interdigital Electrode Pressure Sensor.

Hydrogel-based flexible strain sensors have been known for their excellent ability to convert different motions of humans into electrical signals, thus enabling real-time monitoring of various human health parameters. In this work, a composite hydrogel with hydrophobic association and hybrid cross-linking was fabricated by using polyacrylamide (PAm), surfactant sodium dodecyl sulfate (SDS), lauryl methacrylate (LMA), and polypyrrole (PPy). The dynamic dissociation-conjugation among LMA, SDS, and PPy could dissipate energy to improve the toughness of hydrogels. The SDS/PPy/LMPAm composite hydrogel with a toughness of 1.44 MJ/m3, tensile fracture stress of 345 kPa, tensile strain of 1021%, and electrical conductivity of 0.57 S/m was obtained. Furthermore, an interdigital electrode flexible pressure sensor was designed to replace the bipolar electrode flexible pressure sensor, which greatly improved the sensitivity and resolution of the pressure sensor. The SDS/PPy/LMPAm composite hydrogel-based interdigital electrode flexible pressure sensor showed extraordinary stability and identified different hand gestures as well as monitored the pulse signal of humans. Moreover, the characteristic systolic and diastolic peaks were clearly observed. The pulse frequency (65 times/min) and the radial artery augmentation index (0.57) were calculated, which are very important in evaluating the arterial vessel wall and function of human arteries.

Genomic data revealed inbreeding despite a geographically connected stable effective population size since the Holocene in the protected Formosan Long-Arm Scarab beetle, Cheirotonus formosanus.

Biodiversity conservation is a top priority in the face of global environmental change, and the practical restoration of biodiversity has emerged as a key objective. Nevertheless, the question of how to effectively contribute to biodiversity restoration and identify suitable systems for such efforts continues to present major challenges. By using genome-wide SNP data, our study revealed that populations from different mountain ranges of the Formosan Long-Arm Scarab beetle, a flagship species that receives strict protection, exhibited a single genetic cluster with no subdivision. Additionally, our result implied an association between the demographic history and historical fluctuations in climate and environmental conditions. Furthermore, we showed that, despite a stable and moderately sized effective population over recent history, all the individuals we studied exhibited signs of genetic inbreeding. We argued that the current practice of protecting the species as one evolutionarily significant unit remains the best conservation plan and that recent habitat change may have led to the pattern of significant inbreeding. We closed by emphasizing the importance of conservation genetic studies in guiding policy decisions and highlighting the potential of genomic data for identifying ideal empirical systems for genetic rescue, or assisted gene flow studies.

Early-life exposure to mycotoxin zearalenone exacerbates aberrant immune response, oxidative stress, and mortality of Caenorhabditis elegans under pathogen Bacillus thuringiensis infection.

Zearalenone (ZEN) is a prevalent mycotoxin that severely impacts human and animal health. However, the possible interactions between ZEN exposure, pathogen infection, immune system, and reactive oxygen species (ROS) were rarely investigated. We studied the effects of early-life ZEN (50 µM) exposure on the immune response of Caenorhabditis elegans against Bacillus thuringiensis infection and the associated mechanisms. The transcriptomic responses of C. elegans after early-life ZEN exposure were investigated using RNA sequencing and followed by verification using quantitative PCR analysis. We also investigated the immune responses of the worms through B. thuringiensis killing assays and by measuring oxidative stress. The transcriptomics result showed that early-life exposure to ZEN resulted in 44 differentially expressed genes, 7 of which were protein-coding genes with unknown functions. The Gene Ontology analysis suggested that metabolic processes and immune response were among the most significantly enriched biological processes, and the KEGG analysis suggested that lysosomes and metabolic pathways were the most significantly enriched pathways. The ZEN-exposed worms exhibited significantly reduced survival after 24-h B. thuringiensis infection, reaching near 100% mortality compared to 60% of the controls. Using qRT-PCR assay, we found that ZEN further enhanced the expression of immunity genes lys-6, spp-1, and clec-60 after B. thuringiensis infection. A concurrently enhanced ROS accumulation was also observed for ZEN-exposed worms after B. thuringiensis infection, which was 1.2-fold compared with the controls. Moreover, ZEN exposure further enhanced mRNA expression of catalases (ctl-1 and ctl-2) and increased catalase protein activity after B. thuringiensis exposure compared with their non-exposed counterparts, suggesting an elevated oxidative stress. This study suggests that early-life exposure to mycotoxin zearalenone overstimulates immune responses involving spp-17, clec-52, and clec-56, resulting in excessive ROS production, enhanced oxidative stress as indicated by aggravated ctl expression and activity, and a decline in host resistance to pathogenic infection which ultimately leads to increased mortality under B. thuringiensis infection. Our findings provide evidence that could improve our understanding on the potential interactions between mycotoxin zearalenone and pathogens.

Chemical constituents from the leaves and branches of Wikstroemia chamaedaphne with their activation of latent HIV activities.

A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7-9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 µM and compounds 1, 9-11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.

Deep Deblurring in Teledermatology: Deep Learning Models Restore the Accuracy of Blurry Images' Classification.

Background: Blurry images in teledermatology and consultation increased the diagnostic difficulty for both deep learning models and physicians. We aim to determine the extent of restoration in diagnostic accuracy after blurry images are deblurred by deep learning models. Methods: We used 19,191 skin images from a public skin image dataset that includes 23 skin disease categories, 54 skin images from a public dataset of blurry skin images, and 53 blurry dermatology consultation photos in a medical center to compare the diagnosis accuracy of trained diagnostic deep learning models and subjective sharpness between blurry and deblurred images. We evaluated five different deblurring models, including models for motion blur, Gaussian blur, Bokeh blur, mixed slight blur, and mixed strong blur. Main Outcomes and Measures: Diagnostic accuracy was measured as sensitivity and precision of correct model prediction of the skin disease category. Sharpness rating was performed by board-certified dermatologists on a 4-point scale, with 4 being the highest image clarity. Results: The sensitivity of diagnostic models dropped 0.15 and 0.22 on slightly and strongly blurred images, respectively, and deblurring models restored 0.14 and 0.17 for each group. The sharpness ratings perceived by dermatologists improved from 1.87 to 2.51 after deblurring. Activation maps showed the focus of diagnostic models was compromised by the blurriness but was restored after deblurring. Conclusions: Deep learning models can restore the diagnostic accuracy of diagnostic models for blurry images and increase image sharpness perceived by dermatologists. The model can be incorporated into teledermatology to help the diagnosis of blurry images.

Transgenic expression of a T cell epitope in Strongyloides ratti reveals that helminth-specific CD4+ T cells constitute both Th2 and Treg populations.

Helminths are distinct from microbial pathogens in both size and complexity, and are the likely evolutionary driving force for type 2 immunity. CD4+ helper T cells can both coordinate worm clearance and prevent immunopathology, but issues of T cell antigen specificity in the context of helminth-induced Th2 and T regulatory cell (Treg) responses have not been addressed. Herein, we generated a novel transgenic line of the gastrointestinal nematode Strongyloides ratti expressing the immunodominant CD4+ T cell epitope 2W1S as a fusion protein with green fluorescent protein (GFP) and FLAG peptide in order to track and study helminth-specific CD4+ T cells. C57BL/6 mice infected with this stable transgenic line (termed Hulk) underwent a dose-dependent expansion of activated CD44hiCD11ahi 2W1S-specific CD4+ T cells, preferentially in the lung parenchyma. Transcriptional profiling of 2W1S-specific CD4+ T cells isolated from mice infected with either Hulk or the enteric bacterial pathogen Salmonella expressing 2W1S revealed that pathogen context exerted a dominant influence over CD4+ T cell phenotype. Interestingly, Hulk-elicited 2W1S-specific CD4+ T cells exhibited both Th2 and Treg phenotypes and expressed high levels of the EGFR ligand amphiregulin, which differed greatly from the phenotype of 2W1S-specific CD4+ T cells elicited by 2W1S-expressing Salmonella. While immunization with 2W1S peptide did not enhance clearance of Hulk infection, immunization did increase total amphiregulin production as well as the number of amphiregulin-expressing CD3+ cells in the lung following Hulk infection. Altogether, this new model system elucidates effector as well as immunosuppressive and wound reparative roles of helminth-specific CD4+ T cells. This report establishes a new resource for studying the nature and function of helminth-specific T cells.

"Urban Respiration" Revealed by Atmospheric O2 Measurements in an Industrial Metropolis.

Urban regions, which "inhale" O2 from the air and "exhale" CO2 and atmospheric pollutants, including harmful gases and fine particles, are the largest sinks of atmospheric O2, yet long-term O2 measurements in urban regions are currently lacking. In this study, we report continuous measurements of atmospheric O2 in downtown Lanzhou, an industrial metropolis in northwestern China. We found declines in atmospheric O2 associated with deteriorated air quality and robust anticorrelations between O2 and gaseous oxides. By combining O2 and pollutants measurements with a Lagrangian atmospheric transport model, we quantitatively break down "urban respiration" (ΔO2URB) into human respiration (ΔO2RES) and fossil fuel combustion (ΔO2FF). We found increased ΔO2FF contribution (from 66.92% to 72.50%) and decreased ΔO2RES contribution (from 33.08 to 27.50%) as O2 declines and pollutants accumulate. Further attribution of ΔO2FF reveals intracity transport of atmospheric pollutants from industrial sectors and suggests transportation sectors as the major O2 sink in downtown Lanzhou. The varying relationships between O2 and pollutants under different conditions unfold the dynamics of urban respiration and provide insights into the O2 and energy consumption, pollutant emission, and intracity atmospheric transport processes.

One-Pot Synthesis of Dual-Emissive Carbon Dots for Ratiometric Fluorescent Determination of Hg2.

Mercury ion is a global toxic and hazardous environmental pollutant. In this work, a facile and selective ratiometric fluorescent probe was constructed for the detection of mercury ion. The dual-emissive carbon dots (BYCDs) were fabricated by a one-pot hydrothermal method utilizing o-phenylenediamine and glycine as raw materials, and the prepared BYCDs had two independent fluorescence emission peaks at 426 nm and 543 nm under a single excitation wavelength. Based on the change of the intensity ratio of the two fluorescence emission peaks after the addition of Hg2+, a sensitive and selective ratiometric fluorescent probe based on BYCDs was constructed for the detection of Hg2+ with good linearity ranging from 0.95-50 µM and a detection limit of 0.27 µM. In addition, the recovery of this probe was satisfactory in the standard addition experiments of real water samples, and it could be applied to the analysis of Hg2+ in real water samples.

A Ratiometric Probe Based on Carbon Dots and Calcein & Eu3+ for the Fluorescent Detection of Sodium Tripolyphosphate.

Sodium tripolyphosphate, a food additive, is applied broadly in food industry. However, excessive accumulation of sodium tripolyphosphate can result in electrolyte abnormality of the body. Therefore, it is of great importance to investigate an effective method for the detection of sodium tripolyphosphate. In this work, nitrogen-doped carbon dots (NCDs) with constant fluorescence were fabricated using a domestic microwave oven. A ratiometric fluorescent probe was constructed in which NCDs were as internal standard, calcein & Eu3+ were as the detection signal. The fluorescence of calcein at 515 nm was quenched by Eu3+, whereas the emission peak of NCDs at 446 nm was almost unchanged. Additionally, the fluorescence of calcein was recovered because of the strong interaction of sodium tripolyphosphate and Eu3+. The linear range for sodium tripolyphosphate was 0.5-6 µmol/L with detection limit of 0.12 µmol/L. Furthermore, the ratiometric fluorescent probe was applied for sodium tripolyphosphate detection in real milk samples.

Testing the efficacy of different molecular tools for parasite conservation genetics: a case study using horsehair worms (Phylum: Nematomorpha).

In recent years, parasite conservation has become a globally significant issue. Because of this, there is a need for standardized methods for inferring population status and possible cryptic diversity. However, given the lack of molecular data for some groups, it is challenging to establish procedures for genetic diversity estimation. Therefore, universal tools, such as double-digest restriction-site-associated DNA sequencing (ddRADseq), could be useful when conducting conservation genetic studies on rarely studied parasites. Here, we generated a ddRADseq dataset that includes all 3 described Taiwanese horsehair worms (Phylum: Nematomorpha), possibly one of the most understudied animal groups. Additionally, we produced data for a fragment of the cytochrome c oxidase subunit I (COXI) for the said species. We used the COXI dataset in combination with previously published sequences of the same locus for inferring the effective population size (Ne) trends and possible population genetic structure.We found that a larger and geographically broader sample size combined with more sequenced loci resulted in a better estimation of changes in Ne. We were able to detect demographic changes associated with Pleistocene events in all the species. Furthermore, the ddRADseq dataset for Chordodes formosanus did not reveal a genetic structure based on geography, implying a great dispersal ability, possibly due to its hosts. We showed that different molecular tools can be used to reveal genetic structure and demographic history at different historical times and geographical scales, which can help with conservation genetic studies in rarely studied parasites.

Protein O-GlcNAcylation in cardiovascular diseases.

O-GlcNAcylation is a post-translational modification of protein in response to genetic variations or environmental factors, which is controlled by two highly conserved enzymes, i.e. O-GlcNAc transferase (OGT) and protein O-GlcNAcase (OGA). Protein O-GlcNAcylation mainly occurs in the cytoplasm, nucleus, and mitochondrion, and it is ubiquitously implicated in the development of cardiovascular disease (CVD). Alterations of O-GlcNAcylation could cause massive metabolic imbalance and affect cardiovascular function, but the role of O-GlcNAcylation in CVD remains controversial. That is, acutely increased O-GlcNAcylation is an adaptive heart response, which temporarily protects cardiac function. While it is harmful to cardiomyocytes if O-GlcNAcylation levels remain high in chronic conditions or in the long run. The underlying mechanisms include regulation of transcription, energy metabolism, and other signal transduction reactions induced by O-GlcNAcylation. In this review, we will focus on the interactions between protein O-GlcNAcylation and CVD, and discuss the potential molecular mechanisms that may be able to pave a new avenue for the treatment of cardiovascular events.