Search

Jialing Niu,1,2 Jiangtao Liang,3 Qi Feng,2 Mei Wang,2 Luoyu Wang,4 Xiuhong Ge,2 Xiao Wang,5 Zhongxiang Ding2,6 1Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Hangzhou Universal Medical Imaging Diagnostic Center, Hangzhou, People’s Republic of China; 4Institutes of Psychological Sciences, Hangzhou Normal University, Hangzhou, People’s Republic of China; 5Department of Radiology, Wenrong Hospital of Hengdian, Jinhua, People’s Republic of China; 6Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xiao Wang; Zhongxiang Ding Email 398043951@qq.com; hangzhoudzx73@126.comIntroduction: Langerhans cell histiocytosis (LCH) is a histiocytic proliferative disease without a well-understood etiology. The aim of our study is to summarize the imaging features of PET/MR in children with LCH and to explore its diagnostic role in LCH.Methods: Retrospective analysis was performed of the pretreatment PET/MR imaging data of 15 children with LCH. Comparison of ADC values was done between lesions and normal tissues.Results: Of the fifteen patients enrolled, five had single-organ or single-system involvement, and ten had multiple-system involvement. Nine patients had varying degrees of bone destruction and increased FDG uptake, whereas thickening and deviation of the pituitary stalk and disappearance of the normal high-signal intensity of T1WI in the neurohypophysis were observed in the pituitary gland in six of them. Splenomegaly with diffuse increased FDG uptake or a normal spleen with increased FDG uptake was found in four cases, liver in three, multiple lymph node enlargement in three, pulmonary lesions in three, and increased metabolism in medullary cavity in two cases. Additionally, two cases involved the skin. Hypermetabolic nodules were detected in muscle in one case, thyroid involvement in one case, and a mediastinal lesion in one case.Conclusion: PET/MR can show well the distribution of the organs, systems, and lesions involved in LCH and is of considerable significance in the systemic evaluation of LCH.Keywords: LCH, PET/MR, fluorodeoxyglucose F18, imaging, histiocytosis, eliminate imaging

Mosquitoes are vectors of dangerous human diseases such as malaria, dengue, Zika, West Nile fever, and lymphatic filariasis. Visualization of the linear and spatial organization of mosquito chromosomes is important for understanding genome structure and function. Utilization of chromosomal inversions as markers for population genetics studies yields insights into mosquito adaptation and evolution. Cytogenetic approaches assist with the development of chromosome-scale genome assemblies that are useful tools for studying mosquito biology and for designing novel vector control strategies. Fluorescence in situ hybridization is a powerful technique for localizing specific DNA sequences within the linear chromosome structure and within the spatial organization of the cell nucleus. Here, we introduce protocols used in our laboratories for chromosome visualization and their application in mosquitoes.

The complex structure of a pool-type sodium-cooled fast reactor may lead to uncertainty and asymmetry of flow and temperature field distributions under a pump stuck accident. This phenomenon has ob...

Genes that originate during evolution are an important source of novel biological functions. Retrogenes are functional copies of genes produced by retroduplication and as such are located in different genomic positions. To investigate retroposition patterns and retrogene expression, we computationally identified interchromosomal retroduplication events in nine portions of the phylogenetic history of malaria mosquitoes, making use of species that do or do not have classical sex chromosomes to test the roles of sex-linkage. We found 40 interchromosomal events and a significant excess of retroduplications from the X chromosome to autosomes among a set of young retrogenes. These young retroposition events occurred within the last 100 million years in lineages where all species possessed differentiated sex chromosomes. An analysis of available microarray and RNA-seq expression data for Anopheles gambiae showed that many of the young retrogenes evolved male-biased expression in the reproductive organs. Young autosomal retrogenes with increased meiotic or postmeiotic expression in the testes tend to be male biased. In contrast, older retrogenes, i.e., in lineages with undifferentiated sex chromosomes, do not show this particular chromosomal bias and are enriched for female-biased expression in reproductive organs. Our reverse-transcription PCR data indicates that most of the youngest retrogenes, which originated within the last 47.6 million years in the subgenus Cellia, evolved non-uniform expression patterns across body parts in the males and females of An. coluzzii. Finally, gene annotation revealed that mitochondrial function is a prominent feature of the young autosomal retrogenes. We conclude that mRNA-mediated gene duplication has produced a set of genes that contribute to mosquito reproductive functions and that different biases are revealed after the sex chromosomes evolve. Overall, these results suggest potential roles for the evolution of meiotic sex chromosome inactivation in males and of sexually antagonistic conflict related to mitochondrial energy function as the main selective pressures for X-to-autosome gene reduplication and testis-biased expression in these mosquito lineages. Published version

Chromosomes are hierarchically folded within cell nuclei into territories, domains and subdomains, but the functional importance and evolutionary dynamics of these hierarchies are poorly defined. Here, we comprehensively profile genome organizations of five Anopheles mosquito species and show how different levels of chromatin architecture influence each other. Patterns observed on Hi-C maps are associated with known cytological structures, epigenetic profiles, and gene expression levels. Evolutionary analysis reveals conservation of chromatin architecture within synteny blocks for tens of millions of years and enrichment of synteny breakpoints in regions with increased genomic insulation. However, in-depth analysis shows a confounding effect of gene density on both insulation and distribution of synteny breakpoints, suggesting limited causal relationship between breakpoints and regions with increased genomic insulation. At the level of individual loci, we identify specific, extremely long-ranged looping interactions, conserved for similar to 100 million years. We demonstrate that the mechanisms underlying these looping contacts differ from previously described Polycomb-dependent interactions and clustering of active chromatin. NSF [MCB-1715207]; NIH NIAID [R21AI135298, R21AI159382]; USDA National Institute of Food and Agriculture Hatch project [223822]; RFBR [19-34-50051]; University of Lausanne Department of Ecology and Evolution; NIH [AI133571, AI121284]; Novartis Foundation [18B116]; Swiss National Science Foundation [PP00P3_170664, PP00P3_202669]; Fulbright Foreign Student Program [15161026]; Ministry of Education and Science of Russian Federation [2019-0546 (FSUS-2020-0040)]; [121031800061-7] Published version The following reagents were obtained through BEI Resources, NIAID, NIH: An. coluzzii, Strain MOPTI, Eggs, MRA-763, contributed by Gregory C. Lanzaro; An. merus, Strain MAF, MRA-1156, contributed by Maureen Coetzee; An. atroparvus, Strain EBRO, Eggs, MRA-493, contributed by Carlos Aranda and Mark Q. Benedict; An. albimanus, Strain STECLA, Eggs, MRA-126, contributed by Mark Q. Benedict. All computations were performed using nodes of the high-throughput cluster of the Novosibirsk State University, and bioinformatics resource center of the Institute of Cytology and Genetics. We are sincerely grateful to Nariman Battulin for fruitful discussions. This work was supported by the NSF grant MCB-1715207, NIH NIAID grants R21AI135298 and R21AI159382, and the USDA National Institute of Food and Agriculture Hatch project 223822 to IVS. The reported study of An. atroparvus was partly funded by RFBR according to the research project no 19-34-50051 to IVS and VL. PacBio sequencing of An. merus was funded by a grant from the University of Lausanne Department of Ecology and Evolution to RMW and NIH grants AI133571 and AI121284 to Z.T. M.J.M.F.R., L.R., R.F., and R.M.W. were supported by Novartis Foundation for medical-biological research grant #18B116 and Swiss National Science Foundation grants PP00P3_170664 and PP00P3_202669. V.L. was partly supported by the Fulbright Foreign Student Program, Grantee ID: 15161026. Hi-C data analysis was supported by the Ministry of Education and Science of Russian Federation, grant #2019-0546 (FSUS-2020-0040). ChIP-seq data analysis was supported by project 121031800061-7 (Mechanisms of genetic control of development, physiological processes and behavior in animals).

Background Programmed Cell Death 2 Like (PDCD2L) correlates with cell proliferation, apoptosis and mouse embryonic development. However, the role of PDCD2L in human cancers is unclear. Methods Multiple bioinformatic methods, in vitro function experiments and validation were performed to clarify the oncogenic role of PDCD2L in human cancers. Results Our study found that PDCD2L was aberrantly expressed in multiple types of human cancers, and associated with clinical stage and molecular subtype. Furthermore, overexpression of PDCD2L predicted poor overall survival in adrenocortical carcinoma(ACC), kidney chromophobe(KICH), acute myeloid leukemia(LAML), brain lower grade glioma(LGG),liver hepatocellular carcinoma(LIHC), mesothelioma(MESO), uveal melanoma(UVM) and poor diseases free survival in ACC, bladder urothelial carcinoma(BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), kidney renal clear cell carcinoma(KIRC), kidney renal papillary cell carcinoma(KIRP), LGG, LIHC, and UVM. PDCD2L expression was negatively associated with cancer associated fibroblast in breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), sarcoma (SARC), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). Mechanically, we found that PDCD2L expression was associated with apoptosis, invasion and cell cycle by investigating single cell sequencing data. For further validation, PDCD2Lwas highly expressed in colorectal cancer (CRC) cell lines and tissue samples compared with the normal colon cell line and non-tumor adjacent colorectal mucosa tissues. PDCD2L knockdown induced the apoptosis and proliferation of CRC cells. Conclusions Our study shows that the oncogenic role of PDCD2L in various cancers and PDCD2L could be served as a biomarker of CRC.

An anti-embrittlement roadmap Hydrogen is important for energy applications such as fuel cells but tends to diffuse into materials and make them more susceptible to fracture. Chen et al. tackled the challenge of identifying the exact location of hydrogen atoms in two common steels. The light weight and high mobility of hydrogen creates serious problems with conventional techniques. The authors used cryo-transfer atom probe tomography to show that hydrogen is pinned to various interfaces in the steels. This direct look into hydrogen trapping should help with the development of materials that are more resistant to hydrogen embrittlement. Science , this issue p. 171

Haldane’s rule of speciation states that sterility or inviability affects the heterogametic sex of inter-species hybrids. Darwin’s corollary to Haldane’s rule implies that there are asymmetric phenotypes in inter-species hybrids from reciprocal crosses. Studying the phenotypes of F1 hybrids among closely related species of malaria mosquitoes can assist researchers in identifying the genetic factors and molecular mechanisms of speciation. To characterize phenotypes of sterile hybrid males in the Anopheles gambiae complex, we performed crosses between laboratory strains of An. merus and either An. gambiae or An. coluzzii. The reproductive tracts had normal external morphology in hybrid males from crosses between female An. merus and male An. gambiae or An. coluzzii. Despite being sterile, these males could copulate with females for a normal period of time and could transfer a mating plug to induce female oviposition and monogamy. In contrast, the entire reproductive tracts in hybrid males from crosses between female An. gambiae or An. coluzzii and male An. merus were severely underdeveloped. These males had atrophic testes and reduced somatic organs of the reproductive system including male accessary glands and ejaculatory duct. In addition, hybrid males with underdeveloped reproductive tracts displayed a shorter copulation time with females and failed to induce female oviposition and monogamy due to their inability to form and transfer a plug to females during mating. The asymmetry of the phenotypes associated with hybrid male sterility suggests that different genetic factors and molecular mechanisms are responsible for reproductive isolation in reciprocal crosses among species of the An. gambiae complex.

BackgroundAnopheles coluzzii and An. arabiensis belong to the An. gambiae complex and are among the major malaria vectors in Sub-Saharan Africa. However, chromosome-level reference genome assemblies are still lacking for these medically important mosquito species.FindingsIn this study, we produced de novo chromosome-level genome assemblies for An. coluzzii and An. arabiensis using the long-read Oxford Nanopore sequencing technology and the Hi-C scaffolding approach. We obtained 273.4 Mbp and 256.8 Mbp of the total assemblies for An. coluzzii and An. arabiensis, respectively. Each assembly consists of three chromosome-scale scaffolds (X, 2, 3), complete mitochondrion, and unordered contigs identified as autosomal pericentromeric DNA, X pericentromeric DNA, and Y sequences. Comparison of these assemblies with the existing assemblies for these species demonstrated that we obtained improved reference-quality genomes. The new assemblies allowed us to identify genomiccoordinates for the breakpoint regions of fixed and polymorphic chromosomal inversions in An. coluzzii and An. arabiensis.ConclusionThe new chromosome-level assemblies will facilitate functional and population genomic studies in An. coluzzii and An. arabiensis. The presented assembly pipeline will accelerate progress toward creating high-quality genome references for other disease vectors.

Chromosomes are intricately folded within the cell nucleus and interact with peripheral nuclear proteins. The chromatin architecture has a profound effect on how the genome is organized. 3D-FISH is a powerful technique that can reveal the structural and functional organization of chromosomes in the nuclear space. Here, we present a protocol for visualizing specific genomic regions in whole-mount paraformaldehyde-fixed cell nuclei ofAnophelesmosquitoes. This protocol was tested in our laboratories and has been showed to be effective and reliable for visualizing genomic regions of various lengths—from 1-kb gene-scale fragments to chromosome-scale segments of DNA.

Chromosome visualization is a key step for developing cytogenetic maps and idiograms, analyzing inversion polymorphisms, and identifying mosquito species. Three types of chromosomes—polytene, mitotic, and meiotic—are used in cytogenetic studies of mosquitoes. Here, we describe a detailed method for obtaining high-quality polytene chromosome preparations from the salivary glands of larvae and the ovaries of females forAnophelesmosquitoes. We also describe how to obtain mitotic chromosomes from imaginal discs of fourth-instar larvae and meiotic chromosomes from the testes of male pupae for all mosquitoes. These chromosomes can be used for fluorescence in situ hybridization (FISH), a fundamental technique in cytogenetic research that is used for physical genome mapping, detecting chromosomal rearrangements, and studying chromosome organization.

This paper provides an in-depth discussion and analysis of the estimation of nuclear medicine exposure measurements using computerized intelligent processing. The focus is on the study of energy extraction algorithms to obtain a high energy resolution with the lowest possible ADC sampling rate and thus reduce the amount of data. This paper focuses on the direct pulse peak extraction algorithm, polynomial curve fitting algorithm, double exponential function curve fitting algorithm, and pulse area calculation algorithm. The detector output waveforms are obtained with an oscilloscope, and the analysis module is designed in MATLAB. Based on these algorithms, the data obtained from six different lower sampling rates are analyzed and compared with the results of the high sampling rate direct pulse peak extraction algorithm and the pulse area calculation algorithm, respectively. The correctness of the compartment model was checked, and the results were found to be realistic and reliable, which can be used for the analysis of internal exposure data in radiation occupational health management, estimation of internal exposure dose for nuclear emergency groups, and estimation of accidental internal exposure dose. The results of the compartment model of the respiratory tract and the compartment model of the digestive tract can be used to calculate the distribution and retention patterns of radionuclides and their compounds in the body, which can be used to assess the damage of radionuclide internal contamination and guide the implementation of medical treatment.

Chromosomes are hierarchically folded within cell nuclei into territories, domains and subdomains, but the functional importance and evolutionary dynamics of these hierarchies are poorly defined. Here, we comprehensively profiled genome organizations of five Anopheles mosquito species and showed how different levels of chromatin architecture influence contacts between genomic loci. Patterns observed on Hi-C maps are associated with known cytological structures, epigenetic profiles, and gene expression levels. At the level of individual loci, we identified specific, extremely long-ranged looping interactions, conserved for ~100 million years. We showed that the mechanisms underlying these looping contacts differ from previously described Polycomb-dependent interactions and clustering of active chromatin.

In the present study, we design a novel hot stamping steel containing high amounts of C and Si and micro-alloying element (i.e. Nb). The steel was subjected to quenching and partitioning (Q&P) proc...

The opposing and driving forces associated with dynamic transformation in Ti-6Al-4V are evaluated. It is shown that the stored energy is less than the opposing forces inhibiting transformation and insufficient to initiate the phenomenon. By contrast, the driving force derived from the net softening is greater than the opposing force and is responsible for initiating the reaction. This approach indicates that deformation reduces the transus temperature and leads to the formation of a thermodynamically metastable state.

The pool-type sodium-cooled fast reactor decay heat removal system (DHRS) is an important engineered safety system to ensure the establishment of natural circulation in the case of station blackout (SBO). It is of great significance to study characteristics of DHRS for evaluating its passive residual heat removal capacity. Due to numerous core subassemblies and small scale of gaps between subassemblies, it is difficult to use the same scale grids to describe the three-dimensional flow paths in sodium pool with full core. Therefore few researches, either experiments or numerical simulation, have been performed on such complicated phenomena so far. In order to identify the natural circulation flow paths of fast reactor, an integrated three-dimensional simulation model of China Experimental Fast Reactor (CEFR) primary circuit system with full core was established, including 712 subassemblies and small gaps between subassemblies. FLUENT was used to carry out three-dimensional numerical simulation. Through the transient simulation of 5000 s, the main flow paths including the intra-subassembly flow path, the inter-wrapper flow path and the Main Vessel Cooling System (MVCS) backflow path were identified. At 5000 s, the intra-subassembly flow rate, the inter-wrapper flow rate, and the MVCS backflow rate were 3.07 kg/s, 1.53 kg/s, and −1.94 kg/s respectively. The symmetrical thermo-hydraulic characteristics of two loops were obtained to analyze thermal stratification in sodium pool. The results provided a key three-dimensional numerical reference for the safety of CEFR.

One Pump Trip (OPT) may cause asymmetric phenomena in China Experimental Fast Reactor (CEFR) primary system. Not only two loops asymmetric coast-down processes and failure pump backflow, but superposition loss of off-site power (SLOOP) or residual heat removal of single loop (RHROSL) with OPT may make the situation more complicated. In order to investigate transient thermal hydraulic characteristics in sodium pool under OPT-SLOOP and OPT-RHROSL conditions, a full-scale numerical 3D model of sodium pool in CEFR was established, in which the transient processes of coast-down and backflow were simulated. The simulation results revealed that, in the case of OPT-SLOOP, the intact loop overall temperature was significantly higher than the failure loop overall temperature in the cold sodium pool, and the maximum IHX outlet temperature difference between the two loops reached 125.7 ℃, while in the case of OPT-RHROSL, the maximum IHX outlet temperature difference was limited to 15 ℃.

// Jiangtao Liang 1, * , Jianming Tang 1, * , Huijuan Shi 1, * , Hui Li 1 , Tiantian Zhen 1 , Jing Duan 1 , Lili Kang 1 , Fenfen Zhang 1 , Yu Dong 1 and Anjia Han 1 1 Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Anjia Han, email: hananjia@mail.sysu.edu.cn Keywords: miR-27a-3p, RXRα, Wnt/β-catenin pathway, colorectal cancer Received: March 22, 2017 Accepted: July 06, 2017 Published: July 26, 2017 ABSTRACT This study aimed to elucidate how miR-27a-3p modulates the Wnt/β-catenin signaling pathway to promote colorectal cancer (CRC) progression. Our results showed that the expression of miR-27a-3p was up-regulated in CRC and closely associated with histological differentiation, clinical stage, distant metastasis and CRC patients’ survival. miR-27a-3p mimic suppressed apoptosis and promoted proliferation, migration, invasion of CRC cells in vitro and in vivo . Whereas miR-27a-3p inhibitor promoted apoptosis and suppressed proliferation, migration, invasion of CRC cells in vitro and in vivo . Furthermore, RXRα was the target gene of miR-27a-3p in CRC. miR-27a-3p expression negatively correlated with RXRα expression in CRC tissues. The underlining mechanism study showed that miR-27a-3p/RXRα/Wnt/β-catenin signaling pathway is involved in CRC progression. In conclusion, our findings first demonstrate that miR-27a-3p is a prognostic and/or potential therapeutic biomarker for CRC patients and RXRα as miR-27a-3p targeting gene plays an important role in activation of the Wnt/β-catenin pathway during CRC progression.

Hemangioblastomas (HBs) histologically overlap with TFE3 rearrangement-associated tumors, which present as alveolar architecture and clear or eosinophilic granular cytoplasm. However, whether TFE3 is expressed in HBs remains unexplored. Herein, we analyzed the clinicopathologic features of 42 HBs emphasizing studies of TFE3 expression. Of 42 cases, 38 were sporadic and 4 were regarded as a part of von Hippel-Lindau (VHL) syndrome according to clinical presentation. Nineteen patients were male and 23 were female. Patient age ranged from 17 to 70 years (median 43). Tumor size ranged from 0.4 to 4.8 cm (mean 2.2 cm). Follow-up ranged from 1 to 60 months and 6 patients developed recurrence. Immunohistochemistry staining showed that 36 (86%) of 42 HBs expressed TFE3 in nuclei of tumor cells, of which 21 were evaluated as high TFE3 expression levels. Increased TFE3 expression was significantly associated with older ages (P=0.018) and larger tumor size (P=0.001). Seventeen HBs with high TFE3 expression were negative for rearrangement and amplification of TFE3 by FISH analysis, 3 of which including 2 sporadic and 1 VHL-related HBs demonstrated trisomies or tetrasomies of X-chromosome in 7%~18% of tumor cells. All 3 cases occurred in female, presented with a larger tumor size and displayed a similar morphologic appearance with high cellularity and hyperchromatic nuclei. Our study first reports TFE3 expression and its clinicopathological relevance in HBs. We hypothesize that TFE3 might be involved in the pathogenesis of non-VHL-related HBs. Furthermore, HBs with strong TFE3 expression should be differentiated from brain-metastatic TFE3-rearranged tumors.

Poster "Mechanisms of hybrid male sterility in reciprocal crosses between malaria mosquito species."

Spatial organization of chromosome territories and interactions between interphase chromosomes themselves, as well as with the nuclear periphery, play important roles in epigenetic regulation of the genome function. However, the interplay between inter-chromosomal contacts and chromosome-nuclear envelope attachments in an organism&rsquo, s development is not well-understood. To address this question, we conducted microscopic analyses of the three-dimensional chromosome organization in malaria mosquitoes. We employed multi-colored oligonucleotide painting probes, spaced 1 Mb apart along the euchromatin, to quantitatively study chromosome territories in larval salivary gland cells and adult ovarian nurse cells of Anopheles gambiae, An. coluzzii, and An. merus. We found that the X chromosome territory has a significantly smaller volume and is more compact than the autosomal arm territories. The number of inter-chromosomal, and the percentage of the chromosome&ndash, nuclear envelope, contacts were conserved among the species within the same cell type. However, the percentage of chromosome regions located at the nuclear periphery was typically higher, while the number of inter-chromosomal contacts was lower, in salivary gland cells than in ovarian nurse cells. The inverse correlation was considerably stronger for the autosomes. Consistent with previous theoretical arguments, our data indicate that, at the genome-wide level, there is an inverse relationship between chromosome-nuclear envelope attachments and chromosome&ndash, chromosome interactions, which is a key feature of the cell type-specific nuclear architecture.

Quenching and partitioning heat treatment (Q&P) was applied to a cold-rolled high strength steel system (0.28C–1.42Si–4.08Mn, wt%). The quenching temperature was optimized through the constrained carbon equilibrium (CCE) criterion. The effects of austenitizing temperature on the mechanical properties of the experimental steels were systematically investigated. The microstructure was analyzed by means of scanning electron microscopy (SEM), transmission electron microscope (TEM), electron backscatter diffraction (EBSD) and X-ray diffraction (XRD). A significant change of mechanical properties was found when the austenitizing temperature varies from 760 °C to 900 °C with the different microstructure uniformity owning to the prior austenite. The yield strength changes from 1038 MPa to 1276 MPa and the tensile strength changes from 1399 MPa to 1548 MPa, while the elongation changes from 13.4% to 15.6%. By characterizing the retained austenite and analyzing the work hardening behavior, we found that the TRIP effect is heavily linked with the stability of retained austenite during the stretching process. The sustained TRIP effect and uniform microstructure contribute to the exceptional mechanical properties with both high strength and high ductility.

This file contains Supplementary Methods, Supplementary Tables S1-S3, Supplementary Figures S1-S10, Supplementary References

Hybrid male sterility contributes to speciation by restricting gene flow between related taxa at the beginning stages of postzygotic isolation. However, we have limited knowledge about cellular processes and molecular mechanisms that come into play when fertility is first affected. Hybrids between closely related species of the Anopheles gambiae complex offer opportunities to identify spermatogenic errors that arise early during speciation. To investigate possible cellular causes of hybrid male sterility, we performed crosses between sibling species of the An. gambiae complex. Our results demonstrate that testes are severely underdeveloped in hybrids between male An. merus and female An. gambiae or An. coluzzii. No meiotic chromosomes are identified in these hybrid males. However, testes have nearly normal morphologies and sizes but produce mostly nonmotile spermatozoa in hybrids from the reciprocal crosses. Using chromosome X– and Y-specific fluorescent probes, we followed the process of meiosis in each species and their F1 hybrids between female An. merus and male An. gambiae or An. coluzzii. Unlike for pure species, sex chromosomes in meiotic prophase I of F1 hybrids are largely unpaired and all chromosomes show various degrees of insufficient condensation. Instead of entering the reductional division in meiosis I, primary spermatocytes undergo an equational mitotic division producing abnormal diploid sperm. Meiotic chromosomes of some F1 hybrid individuals are involved in de novo genome rearrangements. Yet, the germline-specific genes β2-tubulin, Ams, mts, and Dzip1l express normally in these hybrid males. Thus, our study identified cytogenetic errors in hybrids that arise during the early stages of postzygotic isolation. This knowledge will inform the development of innovative mosquito control strategies based on population suppression by manipulating reproduction via genetic technologies. Author Summary The genetic basis and molecular mechanisms of hybrid male sterility are of considerable interest as they inform our understanding of both speciation and normal fertility function. Studies of sterility in male hybrids between recently evolved species offer opportunities to identify developmental errors that arise early in speciation. We performed crosses between sibling species of the Anopheles gambiae complex to gain insights into a cellular basis of postzygotic isolation. We demonstrate that hybrid male sterility in the malaria mosquitoes is caused by two processes in reciprocal crosses: premeiotic arrest in germline stem cells and the failure of the reductional meiotic division in primary spermatocytes. The meiotic abnormalities also include unpairing of sex chromosomes, chromatin decompaction, and, in some cases, de novo genome rearrangements. The failure of the reductional division in meiosis I results in the production of diploid nonmotile sperm. Despite these meiotic errors, tested germline-specific genes express normally in these hybrid males. Thus, our study identified cellular errors in hybrids that arise during the early stages of postzygotic isolation. Studying molecular mechanisms of the developmental abnormalities in testes of hybrids between closely related species of mosquitoes will improve our knowledge of speciation and empower the sterile insect technique.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Invasion and metastasis are the main cause of mortality in most CRC patients. Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6) regulated glycosylation, which is frequently altered in cancers, and play an important role in cancer development. However, the role of GALNT6 in CRC remains unknown. To investigate the role of GALNT6 in CRC, first we studied correlation of GALNT6 expression levels with outcomes of CRC patients and found CRC patients with higher expression of GALNT6 had a better overall survival than those with lower expression. In addition, GALNT6 expression were significantly associated with tumor size, histological differentiation and lymph node metastasis. In vitro, GALNT6 overexpression dramatically inhibited cellular colony formation, migration, and invasion, and promoted the apoptosis of CRC cells. In vivo, CRC with GALNT6 overexpression showed reduced pulmonary metastasis in recipient mice compared with the controls. GALNT6 expression was significantly increased in SW480 and SW1116 cells cultured in hypoxic condition, and decreased in HT29 and LOVO cells with oxidative stress. Affimetrix microarray analysis showed that GALNT6 overexpression induced 279 genes up-regulated and 215 genes down-regulated in CRC. GALNT6 overexpression dramatically suppressed AKT and activated CD28 signaling pathway in CRC. AKT rescue experiment found that AKT was involved in GALNT6-induced CRC cell migration and invasion. In conclusion, our results first suggest that GALNT6 plays an important role in development and progression of CRC as a tumor suppressor gene.

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. microRNA has been reported playing an important role in a variety of cancers including colorectal cancer. miR-203a-3p has been found up-regulated in CRC tissues compare with the adjacent normal tissues. But, how miR-203a-3p regulates CRC development remains to be elucidated. In this study, gain and loss-of-function assays showed that miR-203a-3p promotes colorectal cancer cell proliferation, colony formation and migration and invasion by targeting PDE4D. And miR-203a-3p/β-catenin/Cyclin D1/c-Myc signaling pathway is involved in the CRC. In summary, this study highlights an onco-miRNA role for miR-203a-3p by regulating PDE4D in CRC and suggests that miR-203a-3p may be a novel molecular therapeutic target for CRC.

Background Anopheles sinensis is a dominant natural vector of Plasmodium vivax in China, Taiwan, Japan, and Korea. Recent genome sequencing of An. sinensis provides important insights into the genomic basis of vectorial capacity. However, the lack of a physical genome map with chromosome assignment and orientation of sequencing scaffolds hinders comparative analyses with other genomes to infer evolutionary changes relevant to the vector capacity. Results Here, a physical genome map for An. sinensis was constructed by assigning 52 scaffolds onto the chromosomes using fluorescence in situ hybridization (FISH). This chromosome-based genome assembly composes approximately 36% of the total An. sinensis genome. Comparisons of 3955 orthologous genes between An. sinensis and Anopheles gambiae identified 361 conserved synteny blocks and 267 inversions fixed between these two lineages. The rate of gene order reshuffling on the X chromosome is approximately 3.2 times higher than that on the autosomes. Conclusions The physical map will facilitate detailed genomic analysis of An. sinensis and contribute to understanding of the patterns and mechanisms of large-scale genome rearrangements in anopheline mosquitoes. Electronic supplementary material The online version of this article (doi:10.1186/s12936-017-1888-7) contains supplementary material, which is available to authorized users.