Biology subjects

Wang, J.-J.

Publications and source records attributed to Wang, J.-J..

28 records · Page 2Linked to original sources

bioRxiv2024

The Neuropeptide Sulfakinin, a peripheral regulator of insect behavior switch between mating and foraging

Behavioral strategies for foraging and reproduction in the oriental fruit fly (Bactrocera dorsalis) are alternative options for resource allocation and are controlled by neuropeptides. Here we show that the behavioral switch between foraging and reproduction is associated with changes in antennal sensitivity. Starved flies became more sensitive to food odors while suppressing their response to opposite-sex pheromones. The gene encoding sulfakinin receptor 1 (SkR1) was significantly upregulated in the antennae of starved flies, so we tested the behavioral phenotypes of null mutants for the genes encoding the receptor (skr1-/-) and its ligand sulfakinin (sk-/-). In both knockout lines, the antennal responses shifted to mating mode even when flies were starved. This suggests that sulfakinin signaling via SkR1 promotes foraging while suppressing mating. Further analysis of the mutant flies revealed that sets of odorant receptor (OR) genes were differentially expressed. Functional characterization of the differentially expressed ORs suggested that sulfakinin directly suppresses the expression of ORs that respond to opposite-sex hormones while enhancing the expression of ORs that detect food volatiles. We conclude that sulfakinin signaling via SkR1, modulating OR expressions and leading to altered antenna sensitivities, is an important component in starvation-dependent behavioral change.

ecology↗

bioRxiv2023

Comparison of Anatomical and Diffusion MRI for detecting Parkinson's Disease using Deep Convolutional Neural Network

Parkinsons disease (PD) is a progressive neurodegenerative disease that affects over 10 million people worldwide. Brain atrophy and microstructural abnormalities tend to be more subtle in PD than in other age-related conditions such as Alzheimers disease, so there is interest in how well machine learning methods can detect PD in radiological scans. Deep learning models based on convolutional neural networks (CNNs) can automatically distil diagnostically useful features from raw MRI scans, but most CNN-based deep learning models have only been tested on T1-weighted brain MRI. Here we examine the added value of diffusion-weighted MRI (dMRI) - a variant of MRI, sensitive to microstructural tissue properties - as an additional input in CNN-based models for PD classification. Our evaluations used data from 3 separate cohorts - from Chang Gung University, the University of Pennsylvania, and the PPMI dataset. We trained CNNs on various combinations of these cohorts to find the best predictive model. Although tests on more diverse data are warranted, deep-learned models from dMRI show promise for PD classification. Clinical RelevanceThis study supports the use of diffusion-weighted images as an alternative to anatomical images for AI-based detection of Parkinsons disease.

neuroscience↗

bioRxiv2023

Genomics-Driven Discovery of Myxopyromides, a Class of Polyketidic Amides Associated with Predation of Myxococcus sp. SDU36

Myxobacteria are renowned for their genuine prowess to deliver multifarious bioactive natural products. Genome mining of Myxococcus sp. SDU36 identified a hybrid PKS-NRPS BGC (mpd) that presumably specified previously uncharacterized molecules. The expression of mpd was activated by exchanging the innate promoter of core PKS-NRPS genes with our recently characterized strong constitutive promoter BBa_J23104. Comparative metabolic profiling allowed facile isolation of the elicited compounds 1-5 designated myxopyromides A-E, a group of structurally related polyketidic amides. Especially, myxopyromides D was appended with an uncommon pyrrolinone warhead at the carboxylic terminus, whereas myxopyromide C was instead decorated with a rare structural unit of aminobutanone. Although myxopyromides basically follow a textbook modular PKS-NRPS biosynthetic trajectory, an anteriorly unappreciated flexible chain release strategy is adopted to enrich the chemical repertoire of mpd BGC. Interestingly, myxopyromides were associated with the predation of Myxococcus sp. SDU36. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/535179v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@29d791org.highwire.dtl.DTLVardef@1079fdcorg.highwire.dtl.DTLVardef@19044d8org.highwire.dtl.DTLVardef@97c7dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2022

LOXL2-dependent deacetylation of aldolase A induces metabolic reprogramming and tumor progression

Lysyl-oxidase like-2 (LOXL2) regulates extracellular matrix remodeling and promotes tumor invasion and metastasis. Altered metabolism is a core hallmark of cancer, however, it remains unclear whether and how LOXL2 contributes to tumor metabolism. Here, we found that LOXL2 and its catalytically inactive L2{Delta}13 splice variant also function as novel deacetylases that trigger metabolic reprogramming during malignant transformation. Integrated transcriptomic and metabolomic analysis revealed that L2{Delta}13-overexpressing transgenic mice displayed perturbed glucose and lipid metabolism, which was associated with increased hepatic fibrosis and enhanced formation of precancerous lesions induced by chemical carcinogens, such as carbon tetrachloride and N-nitrosomethylbenzylamine. Furthermore, both LOXL2 and L2{Delta}13 boosted glucose metabolism of esophageal tumor cells, thereby facilitating tumor cell proliferation in vitro and in vivo. Mechanistically, LOXL2 and L2{Delta}13 interacted physically with several glycolic proteins including aldolase A to enhance their enzymatic activities and mobilization from the actin cytoskeleton. Using SILAC followed by proteomic analysis, we identified LOXL2 as a deacetylase targeting metabolic proteins in esophageal cancer. Importantly, both LOXL2 and L2{Delta}13 directly catalyzed the deacetylation of aldolase A at K13, resulting in enhanced glycolysis which subsequently reprogramed tumor metabolism and promoted tumor progression. High level expression of LOXL2/L2{Delta}13 combined with decreased acetylation of aldolase-K13 predicted poor clinical outcome in patients with esophageal cancer. In summary, we have characterized a novel molecular mechanism that mediates the pro-tumorigenic activity of LOXL2 independently of its classical amine oxidase activity. These findings may enable the future development of therapeutic agents targeting the metabolic machinery via LOXL2 or L2{Delta}13.

cell biology↗

bioRxiv2021

Bone Marrow-Derived AXL Tyrosine Kinase Promotes Mitogenic Crosstalk and Cardiac Allograft Vasculopathy

Cardiac Allograft Vasculopathy (CAV) is a leading contributor to late transplant rejection. Although implicated, the mechanisms by which bone marrow-derived cells promote CAV remain unclear. Emerging evidence implicates the cell surface receptor tyrosine kinase AXL to be elevated in rejecting human allografts. AXL protein is found on multiple cell types, including bone marrow-derived myeloid cells. The causal role of AXL from this compartment and during transplant is largely unknown. This is important because AXL is a key regulator of myeloid inflammation. Utilizing experimental chimeras deficient in the bone marrow-derived Axl gene, we report that Axl antagonizes cardiac allograft survival and promotes CAV. Flow cytometric and histologic analyses of Axl-deficient transplant recipients revealed reductions in both allograft immune cell accumulation and vascular intimal thickness. Co-culture experiments designed to identify cell-intrinsic functions of Axl uncovered complementary cell-proliferative pathways by which Axl promotes CAV-associated inflammation. Specifically, Axl-deficient myeloid cells were less efficient at increasing the replication of both antigen-specific T cells and vascular smooth muscle cells (VSMCs), the latter a key hallmark of CAV. For the latter, we discovered that Axl-was required to amass the VSMC mitogen Platelet-Derived Growth Factor. Taken together, our studies reveal a new role for myeloid Axl in the progression of CAV and mitogenic crosstalk. Inhibition of AXL-protein, in combination with current standards of care, is a candidate strategy to prolong cardiac allograft survival.

immunology↗

bioRxiv2020

The diagnostic value of RASSF1A promoter methylation in prostate cancer: A systematic review and meta-analysis

BackgroundRASSF1A promoter methylation is consistent with clinicopathological data and has good accuracy in distinguishing tumors. However, the diagnostic parameters vary among previous studies. A systematic review was conducted to explore the diagnostic value of RASSF1A promoter methylation in prostate cancer. MethodsA comprehensive search of the literature in the PubMed, Medline, Cochrane Library, Embase and ISI Web of Science databases up to May 21, 2020 was performed. STATA software version 12.0 and Meta-disc version 1.4 were used to analyze the data. ResultsThe pooled sensitivity was 0.64 (95% CI 0.61-0.66), the pooled specificity was 0.80 (95% CI 0.77-0.83), the PLR was 3.82 (95% CI 1.96-7.44), and the NLR was 0.29 (95% CI 0.16-0.52). Furthermore, the pooled DOR of RASSF1A promoter methylation for prostate cancer was 13.08 (95% CI: 6.56-26.08). The area under the summary ROC curve was 0.87 (95% CI: 0.84-0.90). The results of the meta-regression suggested that heterogeneity was mainly derived from publication year. Fagans nomogram showed that the predictive accuracy was increased significantly by detecting RASSF1A promoter methylation for diagnosing prostate cancer. ConclusionThis meta-analysis suggests that detection of the RASSF1A promoter methylation status can be used for the diagnosis of PCa. In the future, further analyses and studies of larger sample sizes in large centers are needed to confirm our conclusion.

cancer biology↗

bioRxiv2019

Influence of age and gender on taste function of healthy subjects

ObjectivesTo determine the influences of age and gender on the taste functions of healthy Taiwanese. MethodsWe evaluated taste functions of healthy Taiwanese using the whole mouth suprathreshold taste test, along with the taste quad test. In the whole-mouth test, we applied in a counterbalanced order sweet, sour, salty, and bitter solutions, each at 5 different suprathreshold concentrations to subjects, who were instructed to sip and swish in mouth twice. Each subject had to indicate the taste quality, and to rate the intensity and unpleasantness/pleasantness of each taste of the solutions. In the quad test, the 4 quadrants of the tongue surface were tested by dripping one concentration of sweet, sour, salty, or bitter solutions for 6 times. Subjects then indicated the taste quality, and rated the intensity of the solution. ResultsSubjects were divided into groups based on their gender and age: 20-39 years, 40-59 years, or [≥] 60 years. We found that in the whole mouth taste test, the total correct identification score dropped with age. But identifying sweet and salty qualities was not affected by age. No differences were found between male and female, except women scored better than men for sweet quality in the age group of 40-59 years. The total correct identification score of the taste quad test also decreased with an increased age of the taste quad test, without gender differences. ConclusionBoth age and gender affected the taste functions in healthy Taiwanese to some extent, and differences were dependent on age, tongue region, and taste quality.

physiology↗

bioRxiv2019

Dissecting the initiation of female meiosis in the mouse at single-cell resolution

Germ cell meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, in mammals, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By comparing the signature gene expression pattern of 4 meiotic germ cell clusters, we found that the 4 cell clusters correspond to different cell status en route to meiosis progression, and therefore, our research here characterized detailed transcriptome dynamics during meiotic prophase I. Reconstructing the progression of meiosis along pseudotime, we identified several new genes and molecular pathways with potential critical roles in the mitosis/meiosis transition and early meiotic progression. Last, the heterogeneity within somatic cell populations was also discussed and different cellular states were identified. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving meiosis initiation and progression in female germ cells and ovarian somatic cells.

developmental biology↗

bioRxiv2019

Transcriptome Landscape Reveals Underlying Mechanisms of Ovarian Cell Fate Differentiation and Primordial Follicle Assembly

Primordial follicle assembly in mammals occurs at perinatal ages and largely determines the ovarian reserve available to support the reproductive lifespan. The primordial follicle structure is generated by a complex network of interactions between oocytes and ovarian somatic cells that remain poorly understood. In the present research, using single-cell RNA sequencing performed over a time-series on mouse ovaries coupled with several bioinformatics analyses, the complete dynamic genetic programs of germ and granulosa cells from E16.5 to PD3 are reported for the first time. The time frame of analysis comprises the breakdown of germ cell cysts and the assembly of primordial follicles. Confirming the previously reported expression of genes by germ cells and granulosa cells, our analyses identified ten distinct gene clusters associated to germ cells and eight to granulosa cells. Consequently, several new genes expressed at significant levels at each investigated stage were assigned. Building single-cell pseudo temporal trajectories five states and two branch points of fate transition for the germ cells, and three states and one branch point for the granulosa cells were revealed. Moreover, GO and ClueGO term enrichment enabled identifying biological processes, molecular functions and cellular components more represented in germ cells and granulosa cells or common to both cell types at each specific stage. Finally, by SCENIC algorithm, we were able to establish a network of regulons that can be postulated as likely candidates for sustaining germ cell specific transcription programs throughout the investigated period.

developmental biology↗

bioRxiv2018

Chronic pain with use of analgesics and mortality in the home healthcare elderly: a nationwide population-based study

BackgroundChronic pain may cause increased complications and all-cause mortality. However, nationwide data on elderly patients receiving home healthcare (HHC) remain unknown. Therefore, we conducted this study to address this issue.\n\nMethodsWe identified elderly individuals ([≥] 65 years) with chronic pain receiving HCC between 2002 and 2013 in the Taiwan National Health Insurance Research Database. The comparisons of the causes of chronic pain, comorbidities, follow-up mortality, and the use of analgesics between two sexes and among three age subgroups were performed.\n\nResultsA total of 1435 participants were identified, with a mean age of 77.8 {+/-} 7.1 years and male percentage of 46.7%. The prevalence of chronic pain was 5.8%. Chronic pain was most prevalent in the 75-84 years age group (46.5%). Malignancy was the most common cause of chronic pain (94.2%), followed by peripheral vascular diseases (6.0%), osteoarthritis (4.3%), pressure ulcer (3.9%), spine diseases (3.1%), osteoporosis (1.3%), and headache (1.3%). The follow-up mortality was 32.8% within 6 month, 64.1% within 1 year, 79.9% within 2 years, and 84.3% within 3 years without difference in two sexes and age subgroups. Acetaminophen was found to be the most common analgesics, followed by non-steroidal anti-inflammatory drugs and opioids. Morphine was the most commonly used opioid.\n\nConclusionsThis study delineates the causes of chronic pain, use of analgesics, and follow-up mortality in the HHC elderly, clarifying the relationship between chronic pain and the HCC elderly. This will facilitate the further investigation of this issue in the future.

epidemiology↗