Biology subjects

Zhang, G.

Publications and source records attributed to Zhang, G..

At least 433 records · Page 24Linked to original sources

bioRxiv2019

Tuber yield and processing quality response of French fried potatoes to nitrogen fertilization

Nitrogen (N) is an important factor that influences potato production; appropriate N fertilizer management can optimize tuber yield and quality and thus reduce the risk of environmental N losses. The present study aimed to evaluate the effects of different nitrogen (N) application rates (0, 75, 150, 225, 300, and 375 kg ha-1) on the total tuber yield, marketable yield, dry matter content, reducing sugar content, sucrose content of tuber, and fry color index of two potato cultivars (Kennebec and Shepody) in 2016 and 2017. N supply significantly affected tuber yield and processing quality, but these effects depended on the year and/or cultivar. The results indicated that low (75 kg ha-1) and medium-N application rates (150 or 225 kg ha-1) had a positive effect on tuber yield and processing quality; however, high-N application rates (300 and 375 kg ha-1) resulted in lower yield and poor quality. Total and marketable yields responded quadratically to N, and they were optimized at 150 kg ha -1 for Kennebec and 225 kg ha-1 for Shepody in both the years. The processing quality of tubers also responded quadratically with increasing N application rates. The optimal range of N application was approximately 145-185.83 kg ha-1 for Kennebec and approximately 93.44-288.67 kg ha-1 for Shepody according to the processing quality standards of French fried potatoes in China. To achieve the goals of high yield and high quality, N application rates should be 150 kg ha-1for Kennebec and 225 kg ha-1 for Shepody.

plant biology↗

bioRxiv2019

Phylogeny, transposable element and sex chromosome evolution of the basal lineage of birds

Sex chromosomes of mammals and most birds are heteromorphic, while those of many paleognaths (ratites and tinamous) are inexplicably homomorphic. To dissect the mechanisms underlying the different tempo of sex chromosome evolution, we produced high-quality genomes of 12 paleognathous species, and reconstructed their phylogeny based on alignments of the non-coding sequences extending to nearly 40% of the genome. Our phylogenomic tree grouped the South American rheas and tinamous together, and supported the independent evolution of gigantism and loss of flight among ratites. The small-bodied tinamous have much higher rates of genome-wide substitutions and transposon turnovers. Yet majorities of both have retained exceptionally long recombining regions occupying over half of the entire sex chromosome, with the rest sex-linked regions diverging from each other at a much lower rate relative to neognathous birds. Each species exhibits a punctuated sequence divergence pattern between sex chromosomes termed evolutionary strata, because of stepwise suppression of recombination. We concluded that all paleognaths share one evolutionary stratum with all other birds, and convergently formed between one to three strata after their rapid speciation. Contrary to the classic notion, we provided clear evidence that the youngest stratum of some tinamous formed without chromosomal inversion. Intriguingly, some of the encompassing W-linked genes have upregulated their expression levels in ovary, probably due to the female-specific selection. We proposed here that the unique male-only parental care system of paleognaths has reduced the intensity of sexual selection, and contributed to these species low rates of sex chromosome evolution. We also provided novel insights into the evolution of W-linked genes at their early stages.

evolutionary biology↗

bioRxiv2019

MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation in Mice

MACF1 is a large crosslinker that contributes to cytoskeleton integrity and cell differentiation. Loss of MACF1 impairs multiple cellular functions in neuron development and epidermal migration, and is the molecular basis for many diseases such as heart failure and Parkinsons disease. MACF1 is highly abundant in bones, however, its involvements in osteogenic differentiation and bone formation are still unknown. In this study, by conditional gene targeting to delete the Macf1 gene specifically in MSCs, we observed ossification retardation and bone loss in MACF1 deficient mice in different developmental stages, which we traced to disorganized cytoskeleton and decreased osteogenic differentiation capability in MSCs. Further, we show that MACF1 interacts and facilitates SMAD7 nuclear translocation to initiate downstream transcription. These findings are hopefully to expand the biological scope of MACF1 in bones, and provide experimental basis for targeting MACF1 in degenerative bone diseases such as osteoporosis.

developmental biology↗

bioRxiv2019

Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)-OGRU via (DSS)6-liposome delivery to the bone formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU can function as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of the OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.

molecular biology↗

bioRxiv2019

Haplotype genetic score analysis in 10,734 mother/infant pairs reveals complex maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes and adult phenotypes

Many maternal traits are associated with a neonates gestational duration, birth weight and birth length. These birth outcomes are subsequently associated with late onset health conditions. Based on 10,734 mother/infant duos of European ancestry, we constructed haplotype genetic scores to dissect the maternal and fetal genetic effects underlying these observed associations. We showed that maternal height and fetal growth jointly affect the duration of gestation - maternal height positively influences the gestational duration, while faster fetal growth reduces gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: tall maternal stature and higher blood glucose causally increase birth size; in the fetus, the height and metabolic risk increasing alleles can lead to increased and decreased birth size respectively; birth weight-raising alleles in fetus may reduce gestational duration and increase maternal blood pressure. These maternal and fetal genetic effects can largely explain the observed associations between the studied maternal phenotypes and birth outcomes as well as the life-course associations between these birth outcomes and adult phenotypes.

genetics↗

bioRxiv2019

Progressive alignment with Cactus: a multiple-genome aligner for the thousand-genome era

Cactus, a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequence. We describe progressive extensions to Cactus that enable reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We show that Cactus is capable of scaling to hundreds of genomes and beyond by describing results from an alignment of over 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment yet created. Further, we show improvements in orthology resolution leading to downstream improvements in annotation.

genomics↗

bioRxiv2019

JMJD6 Cleaves MePCE to Release P-TEFb

More than 30% of genes in higher eukaryotes are regulated by promoter-proximal pausing of RNA polymerase II (Pol II). Phosphorylation of Pol II-CTD by positive transcription elongation factor (P-TEFb) is a necessary precursor event that enables productive transcription elongation. The exact mechanism on how the sequestered P-TEFb is released from the 7SK snRNP complex and recruited to Pol II-CTD remains unknown. In this report, we reveal methylphosphate capping enzyme (MePCE), a core component of the 7SK snRNP complex, as the cognate substrate for Jumonji domain-containing 6 (JMJD6)s novel proteolytic function. Our evidences consist of a crystal structure of JMJD6 bound to methyl-arginine, enzymatic assays of JMJD6 cleaving MePCE in vivo and in vitro, binding assays, and downstream effects of Jmjd6 knockout and overexpression on Pol II-CTD phosphorylation. We propose that JMJD6 assists bromodomain containing 4 (BRD4) to recruit P-TEFb to Pol II-CTD by disrupting the 7SK snRNP complex.

biochemistry↗

bioRxiv2019

Deep sampling of Hawaiian Caenorhabditis elegans reveals high genetic diversity and admixture with global populations

Recent efforts to understand the natural niche of the keystone model organism Caenorhabditis elegans have suggested that this species is cosmopolitan and associated with rotting vegetation and fruits. However, most of the strains isolated from nature have low genetic diversity likely because recent chromosome-scale selective sweeps contain alleles that increase fitness in human-associated habitats. Strains from the Hawaii Islands are highly divergent from non-Hawaiian strains. This result suggests that Hawaiian strains might contain ancestral genetic diversity that was purged from most non-Hawaiian strains by the selective sweeps. To characterize the genetic diversity and niche of Hawaiian C. elegans, we sampled across the Hawaiian Islands and isolated 100 new C. elegans strains. We found that C. elegans strains are not associated with any one substrate but are found in cooler climates at high elevations. These Hawaiian strains are highly diverged compared to the rest of the global population. Admixture analysis identified 11 global populations, four of which are from Hawaii. Surprisingly, one of the Hawaiian populations shares recent ancestry with non-Hawaiian populations, including portions of globally swept haplotypes. This discovery provides the first evidence of gene flow between Hawaiian and non-Hawaiian populations. Most importantly, the high levels of diversity observed in Hawaiian strains might represent the complex patterns of ancestral genetic diversity in the C. elegans species before human influence.

ecology↗

bioRxiv2019

Probiotic strains improve high-fat diet-induced hypercholesterolemia through modulating gut microbiota in ways different from atorvastatin

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics is one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs as like atorvastatin (ATO) both in effectiveness and the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on gut microbiota. Hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, both on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (TNF-, IL-1{beta}, CRP), with strain JQII-5 most significant. Besides, these effects were associated with restoration of the microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genus and reversed genus was found to be correlated to inflammatory state and serum lipid level. Compared with ATO, probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO.

microbiology↗

bioRxiv2019

Identification and evolution of avian endogenous foamy viruses

A history of long-term co-divergence means that foamy viruses (family Retroviridae) provide an ideal framework to understanding virus-host evolution over extended time periods. Endogenous foamy viruses (EndFVs) are rare, and to date have only been described in a limited number of mammals, amphibians, reptiles and fish genomes. By screening 414 avian genomes we identified EndFVs in two bird species: the Maguari Stork (Ciconia maguari) and the Oriental Stork (C. boyciana). Analyses of phylogenetic relationships, genome structures and flanking sequences revealed a single origin of EndFVs in Ciconia species. In addition, the marked incongruence between the virus and host phylogenies suggested that this integration event occurred independently in birds. In sum, by providing evidence that birds can be infected with foamy viruses, we fill the last major gap in the taxonomic distribution of foamy viruses and their animal hosts.

microbiology↗

bioRxiv2019

Development of a PC12 cell-based assay for in vitro screening of catechol-O-methyltransferase inhibitors

The male rat adrenal pheochromocytoma cell-originated PC12 cell line can synthesize and release catecholamine neurotransmitters, and it has been widely used as a model system in cell biology and toxicology research. Catechol-O-methyltransferase (COMT) is involved in the inactivation of the catecholamine neurotransmitters, and it is particularly important for theregulation of dopamine. In this study, we explored the feasibility of using PC12 cells as an in vitro drug screening platform to compare the activity of multiple COMT inhibitors. Incubation of PC12 cells with tolcapone, a highly potent and selective COMT inhibitor, increased the concentrations of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) while reducing the metabolites 3-methoxytyramine (3-MT) and homovanillic acid (HVA) in the cell culture medium. LIBD-3, a novel, non-nitrocatechol COMT inhibitor produced similar effects compared to tolcapone. LIBD-4, a less potent inhibitor, exhibited the expected right-shift in functional inhibition in the assay. These results match the known in vivo effects of COMT inhibition in rodents. Together, these data support the continued use of PC12 cells as an in vitro screen that bridges cell-free enzyme assays and more costly in vivo assays.

neuroscience↗

bioRxiv2019

Adaptive evolution targets a piRNA precursor transcription network

In Drosophila, transposon-silencing piRNAs are derived from heterochromatic clusters and a subset of euchromatic transposon insertions, which are transcribed from internal non-canonical initiation sites and flanking canonical promoters. Rhino binds to Deadlock, which recruits TRF2 to promote non-canonical transcription of these loci. Cuff co-localizes with Rhino and Del. The role of Cuff is less well understood, but the cuff gene shows hallmarks of adaptive evolution, which frequently targets functional interactions within host defense systems. We show that Drosophila simulans cuff is a dominant negative allele when expressed in Drosophila melanogaster, where it traps Deadlock, TRF2 and the transcriptional co-repressor CtBP in stable nuclear complexes. Cuff promotes Rhino and Deadlock localization, driving non-canonical transcription. CtBP, by contrast, suppresses canonical cluster and transposon transcription, which interferes with downstream non-canonical transcription and piRNA production. Cuff, TRF2 and CtBP thus form a network that balances canonical and non-canonical piRNA precursor transcription.

genetics↗

bioRxiv2019

3D observation of large-scale subcellular dynamics in vivo at the millisecond scale

Observing large-scale three-dimensional (3D) subcellular dynamics in vivo at high spatiotemporal resolution has long been a pursuit for biology. However, both the signal-to-noise ratio and resolution degradation in multicellular organisms pose great challenges. Here, we propose a method, termed Digital Adaptive Optics Scanning Lightfield Mutual Iterative Tomography (DAOSLIMIT), featuring both 3D incoherent synthetic aperture and tiled wavefront correction in post-processing. We achieve aberration-free fluorescence imaging in vivo over a 150 x 150 x 16 m3 field-of-view with the spatiotemporal resolution up to 250 nm laterally and 320 nm axially at 100 Hz, corresponding to a huge data throughput of over 15 Giga-voxels per second. Various fast subcellular processes are observed, including mitochondrial dynamics in cultured neurons, membrane dynamics in zebrafish embryos, and calcium propagation in cardiac cells, human cerebral organoids, and Drosophila larval neurons, enabling simultaneous in vivo studies of morphological and functional dynamics in 3D.

cell biology↗

bioRxiv2019

Mitochondrial behaviors prime the selective inheritance against harmful mitochondrial DNA mutations

Although mitochondrial DNA (mtDNA) is prone to mutation and not all conventional DNA repair systems operate in mitochondria, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we use Drosophila to dissect the mechanisms of mtDNA selective inheritance and understand their molecular underpinnings. Our observations support a purifying selection at the organelle level based on a series of developmentally-orchestrated mitochondrial processes. We demonstrate that mitochondrial fission, together with the lack of mtDNA replication in early germarium, effectively segregates mtDNA into individual organelles. After mtDNA segregation, mtDNA transcription begins, which leads to the activation of respiration in each organelle. The expression of mtDNA-encoded genes allows the functional manifestation of different mitochondrial genotypes in heteroplasmic cells, and hence functions as a stress test for each individual genome and sets the stage for the replication competition. We also show that the Balbiani body has a minor role in mtDNA selective inheritance by supplying healthy mitochondria to the pole plasm. The two selection mechanisms may act synergistically to secure the transmission of functional mtDNA through Drosophila oogenesis.

genetics↗

bioRxiv2019

Phenological matching drives wheat pest range shift under climate change

Shifting geographical ranges of crop pests and pathogens in response to climate change pose a threat to food security (1, 2). The orange wheat blossom midge (Sitodiplosis mosellana Gehin) is responsible for significant yield losses in China (3), the worlds largest wheat producer. Here we report that rising temperatures in the North China Plain have resulted in a mean northward range shift of 3.3{degrees} (58.8 km per decade) from the 1950s to 2010s, which accelerated to 91.3 km per decade after 1985 when the highly toxic pesticide hexachlorocyclohexane (HCH) was banned (4). Phenological matching between wheat midge adult emergence and wheat heading in this new expanded range has resulted in greater damage to wheat production. Around $286.5 million worth of insecticides were applied to around 19 million hectares in an attempt to minimize wheat midge damage to crops between 1985 and 2016. Despite use of these pesticides, wheat midge caused losses of greater than 0.95 million metric tons of grain during this period. Our results demonstrate the potential for indirect negative impacts of climate change on crop production and food security, and constitute the first large scale example of plant pest range shift due to global warming.

ecology↗

bioRxiv2019

Functional Genomic Complexity Defines Intratumor Heterogeneity and Tumor Aggressiveness in Liver Cancer

BackgroundChronic inflammation and chromosome aneuploidy are major traits of primary liver cancer (PLC), which represent the second most common cause of cancer related death worldwide. Increased cancer fitness and aggressiveness of PLC may be achieved by enhancing tumoral genomic complexity that alters tumor biology.\n\nMethodHere, we developed a scoring method, namely functional genomic complexity (FGC), to determine the degree of molecular heterogeneity among 580 liver tumors with diverse ethnicities and etiologies by assessing integrated genomic and transcriptomic data.\n\nResultsWe found that tumors with higher FGC scores are associated with chromosome instability and TP53 mutations, and a worse prognosis, while tumors with lower FGC scores have elevated infiltrating lymphocytes and a better prognosis. These results indicate that FGC scores may serve as a surrogate to define genomic heterogeneity of PLC linked to chromosomal instability and evasion of immune surveillance.\n\nConclusionOur findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy.\n\nSTATEMENT OF SIGNIFICANCEGenomic heterogeneity contributes to therapeutic failure and poor outcome in patients with liver cancer and poses a challenge in defining targeted therapy. Our findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy. \\body

genomics↗

bioRxiv2019

Oleocanthal and oleocanthal-rich olive oils induce lysosomal membrane permeabilization in cancer cells

Oleocanthal is a phenolic compound found in varying concentrations in extra virgin olive oil Oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal, as well as naturally oleocanthal-rich extra virgin olive oils, induced damage to cancer cells lysosomes leading to cellular toxicity in vitro and in vivo. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, we found oleocanthal treatment reduced tumor burden and extended lifespan of mice engineered to develop pancreatic neuroendocrine tumors. Finally, following-up on numerous correlative studies demonstrating consumption of olive oil reduces cancer incidence and morbidity, we observed that extra virgin olive oils naturally rich in oleocanthal sharply reduced cancer cell viability and induced lysosomal membrane permeabilization while oleocanthal-poor oils did not. Our results are especially encouraging since tumor cells often have larger and more numerous lysosomes, making them especially vulnerable to lysosomotropic agents such as oleocanthal.

cancer biology↗

bioRxiv2019

Function and clinical relevance of RHAMM isoforms in pancreatic tumor progression

The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers. We previously screened genes upregulated in human hepatocellular carcinomas for their metastatic function in a mouse model of pancreatic neuroendocrine tumor (PNET) and identified that human RHAMMB promoted liver metastasis. It was unknown whether RHAMMB is upregulated in pancreatic cancer or contributes to its progression. In this study, we found that RHAMM protein was frequently upregulated in human PNETs. We investigated alternative splicing isoforms, RHAMMA and RHAMMB, by RNA-Seq analysis of primary PNETs and liver metastases. RHAMMB, but not RHAMMA, was significantly upregulated in liver metastases. RHAMMB was crucial for in vivo metastatic capacity of mouse and human PNETs. RHAMMA, carrying an extra 15-amino acid-stretch, did not promote metastasis in spontaneous and experimental metastasis mouse models. Moreover, RHAMMB was substantially higher than RHAMMA in pancreatic ductal adenocarcinoma (PDAC). RHAMMB, but not RHAMMA, correlated with both higher EGFR expression and poorer survival of PDAC patients. Knockdown of EGFR abolished RHAMMB-driven PNET metastasis. Altogether, our findings suggest a clinically relevant function of RHAMMB, but not RHAMMA, in promoting PNET metastasis in part through EGFR signaling. RHAMMB can thus serve as a prognostic factor for pancreatic cancer.

cancer biology↗