Full-range depth-encoded swept source polarization sensitive optical coherence tomography.

To realize the high sensitivity polarization sensitive optical coherence tomography (PS-OCT) imaging, a fiber-based full-range depth-encoded swept source PS-OCT (SS-PS-OCT) method is proposed. The two OCT images corresponding to the orthogonal polarized input light are located on the high sensitivity imaging region of the opposite sides relative to the zero optical path difference position. The full-range OCT images can be obtained by implementing the spatial phase modulation in the reference arm.

Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting.

PHF6 mutations (PHF6) are identified in various myeloid neoplasms (MN). However, little is known about the precise function and consequences of PHF6 in MN. Here we show three main findings in our comprehensive genomic and proteomic study.

Local polarization properties extraction using single incident state, single-mode-fiber-based spectral domain polarization-sensitive optical coherence tomography.

We showed the local polarization properties extraction method for the single incident state, all-single-mode-fiber-based spectral domain polarization-sensitive optical coherence tomography (SD-PS-OCT) system that uses the single linear-in-wavenumber spectral camera. Polarization controllers are used in the single-mode-fiber-based SD-PS-OCT system to provide a compact structure with polarization state stability. The local polarization properties of the birefringent sample are extracted from the cumulative polarization properties iteratively.

Polarization-multiplexed, single-cavity dual-comb fiber laser based on a birefringent crystal and a saturable absorber.

We introduce a calcium carbonate birefringent crystal into an Er-fiber laser mode-locked by a saturable absorber, where dual-comb ultrashort pulses with orthogonal polarization have been obtained. The two ultrashort pulse trains from the laser exhibit polarization contrast ratios of 30 dB and 20 dB, indicating that the dual-comb mode-locking is due to the polarization-multiplexing mechanism. The dual-comb ultrashort pulses have central wavelengths of 1564.

PBRM1 loss in kidney cancer unbalances the proximal tubule master transcription factor hub to repress proximal tubule differentiation.

PBRM1, a subunit of the PBAF coactivator complex that transcription factors use to activate target genes, is genetically inactivated in almost all clear cell renal cell cancers (RCCs). Using unbiased proteomic analyses, we find that PAX8, a master transcription factor driver of proximal tubule epithelial fates, recruits PBRM1/PBAF. Reverse analyses of the PAX8 interactome confirm recruitment specifically of PBRM1/PBAF and not functionally similar BAF.

Therapeutic Targeting of Protein Disulfide Isomerase PDIA1 in Multiple Myeloma.

Multiple myeloma is a genetically complex hematologic neoplasia in which malignant plasma cells constantly operate at the maximum limit of their unfolded protein response (UPR) due to a high secretory burden of immunoglobulins and cytokines. The endoplasmic reticulum (ER) resident protein disulfide isomerase, PDIA1 is indispensable for maintaining structural integrity of cysteine-rich antibodies and cytokines that require accurate intramolecular disulfide bond arrangement. PDIA1 expression analysis from RNA-seq of multiple myeloma patients demonstrated an inverse relationship with survival in relapsed or refractory disease, supporting its critical role in myeloma persistence.

Functional analyses of human LUC7-like proteins involved in splicing regulation and myeloid neoplasms.

Vertebrates have evolved three paralogs, termed LUC7L, LUC7L2, and LUC7L3, of the essential yeast U1 small nuclear RNA (snRNA)-associated splicing factor Luc7p. We investigated the mechanistic and regulatory functions of these putative splicing factors, of which one (LUC7L2) is mutated or deleted in myeloid neoplasms. Protein interaction data show that all three proteins bind similar core but distinct regulatory splicing factors, probably mediated through their divergent arginine-serine-rich domains, which are not present in Luc7p.

'You are not Young Anymore!': Gender, Age and the Politics of Reproduction in Post-reform China.

Based on in-depth interview data and popular culture texts, the current study has explored the politics of reproduction revolving around women's age in contemporary China. Conceptualizing reproduction as a site of contestation and politics between different, and often contradictory, sets of discourses and power structures, I pursue a feminist and social constructivist analysis of the politics of reproduction in the lives of a group of urban professional women who are yet to enter motherhood at their late 20s and 30s. I engage with Inhorn's (2009) concept of 'disrupted reproduction' to highlight the politically, morally and emotionally charged contestations in the 'problematized' reproductive lives of these women.

Artificial intelligence-assisted auscultation in detecting congenital heart disease.

Aims: Computer-assisted auscultation has become available to assist clinicians with physical examinations to detect congenital heart disease (CHD). However, its accuracy and effectiveness remain to be evaluated. This study seeks to evaluate the accuracy of auscultations of abnormal heart sounds of an artificial intelligence-assisted auscultation (AI-AA) platform we create.

Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck.

Avian eggshell color is an interesting genetic trait. Here, we report that the blue eggshell color of the domestic duck is caused by two cis-regulatory G to A transitions upstream of ABCG2, which encodes an efflux transporter. The juxtaposed blue eggshell allele A-A exhibited higher promoter activity and stronger nuclear protein binding capacity than the white eggshell allele G-G.

A pilot clinical trial of the cytidine deaminase inhibitor tetrahydrouridine combined with decitabine to target DNMT1 in advanced, chemorefractory pancreatic cancer.

DNA methyltransferase 1 (DNMT1) is scientifically validated as a molecular target to treat chemo-resistant pancreatic ductal adenocarcinoma (PDAC). Results of clinical studies of the pyrimidine nucleoside analog decitabine to target DNMT1 in PDAC have, however, disappointed. One reason is high expression in PDAC of the enzyme cytidine deaminase (CDA), which catabolizes decitabine within minutes.

Context dependent effects of ascorbic acid treatment in TET2 mutant myeloid neoplasia.

Loss-of-function TET2 mutations (TET2) are common in myeloid neoplasia. TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. TET2 thus result in hypermethylation and transcriptional repression.

Decitabine- and 5-azacytidine resistance emerges from adaptive responses of the pyrimidine metabolism network.

Mechanisms-of-resistance to decitabine and 5-azacytidine, mainstay treatments for myeloid malignancies, require investigation and countermeasures. Both are nucleoside analog pro-drugs processed by pyrimidine metabolism into a deoxynucleotide analog that depletes the key epigenetic regulator DNA methyltranseferase 1 (DNMT1). Here, upon serial analyses of DNMT1 levels in patients' bone marrows on-therapy, we found DNMT1 was not depleted at relapse.

A Discovery of a Genetic Mutation Causing Reduction of Atrogin-1 Expression in Broiler Chicken Muscle.

Chickens are bred all over the world and have significant economic value as one of the major agricultural animals. The growth rate of commercial broiler chickens is several times higher than its Red Jungle fowl (RJF) ancestor. To further improve the meat production of commercial chickens, it is quite important to decipher the genetic mechanism of chicken growth traits.

Cytokine-Regulated Phosphorylation and Activation of TET2 by JAK2 in Hematopoiesis.

Even though the Ten-eleven translocation (TET) enzymes catalyze the generation of 5-hydroxymethylcytosines required for lineage commitment and subsequent differentiation of stem cells into erythroid cells, the mechanisms that link extracellular signals to TET activation and DNA hydroxymethylation are unknown. We demonstrate that hematopoietic cytokines phosphorylate TET2, leading to its activation in erythroid progenitors. Specifically, cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines 1939 and 1964.

OAS-RNase L innate immune pathway mediates the cytotoxicity of a DNA-demethylating drug.

Drugs that reverse epigenetic silencing, such as the DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (AZA), have profound effects on transcription and tumor cell survival. AZA is an approved drug for myelodysplastic syndromes and acute myeloid leukemia, and is under investigation for different solid malignant tumors. AZA treatment generates self, double-stranded RNA (dsRNA), transcribed from hypomethylated repetitive elements.

Leukemogenic nucleophosmin mutation disrupts the transcription factor hub that regulates granulomonocytic fates.

Nucleophosmin (NPM1) is among the most frequently mutated genes in acute myeloid leukemia (AML). It is not known, however, how the resulting oncoprotein mutant NPM1 is leukemogenic. To reveal the cellular machinery in which NPM1 participates in myeloid cells, we analyzed the endogenous NPM1 protein interactome by mass spectrometry and discovered abundant amounts of the master transcription factor driver of monocyte lineage differentiation PU.

Polygenic Basis and Variable Genetic Architectures Contribute to the Complex Nature of Body Weight -A Genome-Wide Study in Four Chinese Indigenous Chicken Breeds.

Body weight (BW) is one of the most important economic traits for animal production and breeding, and it has been studied extensively for its phenotype-genotype associations. While mapping studies have mostly aimed at finding as many loci as possible that contributed to the variation in BW, the role of other factors in its genetic architecture, including their frequencies in the population and their interactions, have been largely overlooked. To comprehensively characterized the genetic architecture of BW, we performed a genome-wide association study (GWAS) both at the single-marker and haplotype level on birds from four indigenous Chinese chicken breeds (Chahua, Silkie, Langshan, and Beard), rather than studying crosses between two founder lines.

GATA4 loss of function in liver cancer impedes precursor to hepatocyte transition.

The most frequent chromosomal structural loss in hepatocellular carcinoma (HCC) is of the short arm of chromosome 8 (8p). Genes on the remaining homologous chromosome, however, are not recurrently mutated, and the identity of key 8p tumor-suppressor genes (TSG) is unknown. In this work, analysis of minimal commonly deleted 8p segments to identify candidate TSG implicated GATA4, a master transcription factor driver of hepatocyte epithelial lineage fate.

A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens.

Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8.

Genome-wide DNA methylome variation in two genetically distinct chicken lines using MethylC-seq.

Background: DNA cytosine methylation is an important epigenetic modification that has significant effects on a variety of biological processes in animals. Avian species hold a crucial position in evolutionary history. In this study, we used whole-genome bisulfite sequencing (MethylC-seq) to generate single base methylation profiles of lungs in two genetically distinct and highly inbred chicken lines (Fayoumi and Leghorn) that differ in genetic resistance to multiple pathogens, and we explored the potential regulatory role of DNA methylation associated with immune response differences between the two chicken lines.

Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms.

Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations.

A cis-regulatory mutation of PDSS2 causes silky-feather in chickens.

Silky-feather has been selected and fixed in some breeds due to its unique appearance. This phenotype is caused by a single recessive gene (hookless, h). Here we map the silky-feather locus to chromosome 3 by linkage analysis and subsequently fine-map it to an 18.

Runx1 regulation of Pu.1 corepressor/coactivator exchange identifies specific molecular targets for leukemia differentiation therapy.

Gene activation requires cooperative assembly of multiprotein transcription factor-coregulator complexes. Disruption to cooperative assemblage could underlie repression of tumor suppressor genes in leukemia cells. Mechanisms of cooperation and its disruption were therefore examined for PU.