Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma

<p>Abstract</p> <p>Background</p> <p>Diagnosis of ductal carcinoma in situ (DCIS) in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs) are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-α), and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-α may be helpful in determining whether DCIS has microinvasion.</p> <p>Methods</p> <p>349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-α, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH); group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI), and group 5: invasive ductal carcinoma (IDC). A comparative evaluation of the four immunostains was conducted.</p> <p>Results</p> <p>Our results demonstrated that using FAP-α and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP-α and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%.</p> <p>Conclusions</p> <p>This study provides the first evidence that immunostaining with FAP-α and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion.</p

Identification and Functional Analysis of ThADH1 and ThADH4 Genes Involved in Tolerance to Waterlogging Stress in Taxodium hybrid ‘Zhongshanshan 406’

The Taxodium hybrid ‘Zhongshanshan 406’ (T. hybrid ‘Zhongshanshan 406’) [Taxodium mucronatum Tenore × Taxodium distichum (L.). Rich] has an outstanding advantage in flooding tolerance and thus has been widely used in wetland afforestation in China. Alcohol dehydrogenase genes (ADHs) played key roles in ethanol metabolism to maintain energy supply for plants in low-oxygen conditions. Two ADH genes were isolated and characterized—ThADH1 and ThADH4 (GenBank ID: AWL83216 and AWL83217—basing on the transcriptome data of T. hybrid ‘Zhongshanshan 406’ grown under waterlogging stress. Then the functions of these two genes were investigated through transient expression and overexpression. The results showed that the ThADH1 and ThADH4 proteins both fall under ADH III subfamily. ThADH1 was localized in the cytoplasm and nucleus, whereas ThADH4 was only localized in the cytoplasm. The expression of the two genes was stimulated by waterlogging and the expression level in roots was significantly higher than those in stems and leaves. The respective overexpression of ThADH1 and ThADH4 in Populus caused the opposite phenotype, while waterlogging tolerance of the two transgenic Populus significantly improved. Collectively, these results indicated that genes ThADH1 and ThADH4 were involved in the tolerance and adaptation to anaerobic conditions in T. hybrid ‘Zhongshanshan 406’

Meat and bone meal stimulates microbial diversity and suppresses plant pathogens in asparagus straw composting

Meat and bone meal (MBM), as slaughterhouse waste, is a potential biostimulating agent, but its efficiency and reliability in composting are largely unknown. To access the MBM application to the composting process of asparagus straw rice, we followed the composting process for 60 days in 220-L composters and another 180 days in 20-L buckets in treatments applied with MBM or urea. The microbial succession was investigated by high-throughput sequencing. Compared with urea treatments, MBM addition stabilized pH and extended the thermophilic phase for 7 days. The germination index of MBM treatments was 24.76% higher than that of urea treatments. MBM also promoted higher microbial diversity and shifted community compositions. Organic matter and pH were the most significant factors that influence the bacterial and fungal community structure. At the genus level, MBM enriched relative abundances of organic matter-degrading bacteria (Alterococcus) and lignocellulose-degrading fungi (Trichoderma), as well as lignocellulolytic enzyme activities. Notably, MBM addition decreased sum abundances of plant pathogenic fungi of Phaeoacremonium, Acremonium, and Geosmithia from 17.27 to 0.11%. This study demonstrated the potential of MBM as an effective additive in asparagus straw composting, thus providing insights into the development of new industrial aerobic fermentation.Peer reviewe

PDIP46 (DNA Polymerase Delta Interacting Protein 46) Is an Activating Factor for Human DNA Polymerase Delta

PDIP46 (SKAR, POLDIP3) was discovered through its interaction with the p50 subunit of human DNA polymerase δ (Pol δ). Its functions in DNA replication are unknown. PDIP46 associates with Pol δ in cell extracts both by immunochemical and protein separation methods, as well as by ChIP analyses. PDIP46 also interacts with PCNA via multiple copies of a novel PCNA binding motif, the APIMs (AlkB homologue-2 PCNA-Interacting Motif). Sites for both p50 and PCNA binding were mapped to the N-terminal region containing the APIMs. Functional assays for the effects of PDIP46 on Pol δ activity on singly primed ssM13 DNA templates revealed that it is a novel and potent activator of Pol δ. The effects of PDIP46 on Pol δ in primer extension, strand displacement and synthesis through simple hairpin structures reveal a mechanism where PDIP46 facilitates Pol δ4 synthesis through regions of secondary structure on complex templates. In addition, evidence was obtained that PDIP46 is also capable of exerting its effects by a direct interaction with Pol δ, independent of PCNA. Mutation of the Pol δ and PCNA binding region resulted in a loss of PDIP46 functions. These studies support the view that PDIP46 is a novel accessory protein for Pol δ that is involved in cellular DNA replication. This raises the possibility that altered expression of PDIP46 or its mutation may affect Pol δ functions in vivo, and thereby be a nexus for altered genomic stability

Evolutionary Analyses Reveal Diverged Patterns of SQUAMOSA Promoter Binding Protein-Like (SPL) Gene Family in Oryza Genus

The SPL (SQUAMOSA promoter binding protein-like) gene family is one of the plant-specific transcription factor families and controls a considerable number of biological functions, including floral development, phytohormone signaling, and toxin resistance. However, the evolutionary patterns and driving forces of SPL genes in the Oryza genus are still not well-characterized. In this study, we investigated a total of 105 SPL genes from six AA genome Oryza representative species (O. barthii, O. glumipatula, O. nivara, O. rufipogon, O. glaberrima, and O. sativa). Phylogenetic and motif analyses indicated that SPL proteins could be divided into two distinct lineages (I and II), and further studies showed lineage II consisted of three clades (IIA, IIB, and IIC). We found that clade I had comparable structural features with clade IIA, whereas genes in clade IIC displayed intrinsic differences, such as lower exon numbers and the presence of miR156 regulation elements. Nineteen orthologous groups of OsSPLs in Oryza were also identified, and most exons within those genes maintained constant length, whereas length of intron changed relatively. All groups were constrained by stronger purifying selection and diversified continually including alterative gene number, intron length, and miR156 regulation. Subsequently, cis-acting element analyses revealed the potential role of SPLs in wild rice, which might participate in light-responsive, phytohormone response, and plant growth and development. Our results shed light on that different evolutionary rates and duplication events might result in divergent evolutionary patterns in each lineage of SPL genes, providing a guide in exploring diverse function in the rice gene family among six closely related Oryza species

The Tapes Complex (Nico Pérez Terrane, Uruguay): Constraining the Mesoproterozoic evolution of the Río de la Plata Craton

The Tapes Complex crops out in the southeastern Nico Pérez Terrane (NPT) of the Río de la Plata Craton and forms part of a NE-trending Mesoproterozoic belt together with the Calymmian (1.48–1.43 Ga) Parque UTE and Mina Verdún groups. The complex is characterized by interbedded/tectonically interleaved metasedimentary (mainly siliciclastic) and metaultramafic rocks, with subordinate intercalations of metabasites, carbonate and chert, all metamorphosed in the greenschist facies. The age of the Tapes Complex is constrained by: (i) a U–Pb SIMS age of 1360 ± 12 Ma for the youngest detrital zircon, (ii) the K–Ar age of 1253 ± 32 Ma for synkinematic muscovite of the Zapicán thrust, which affects the unit, and (iii) an Sm–Nd isochronic age of 1403 ± 150 Ma for ultramafic and mafic rocks. The intruding Tapes Chico Syenite yielded a much younger U–Pb SIMS age of 601 ± 5 Ma, associated with Brasiliano-Pan African tectonism, negative εHf values (mean = −31), δ18O zircon ratios ranging between 5.45 and 6.68‰ V-SMOW and inherited zircons dated at 1774-1756 Ma. The best preserved mafic and ultramafic samples yielded Nd model ages (TDM) between 1.55 and 1.68 Ga, close to the assumed crystallization age, and positive εNd(t). Nd model ages of metasedimentary rocks vary between 1.8 and 3.1 Ga, which is interpreted as reflecting two contrasting sources: Archean units of the NPT and Mesoproterozoic mafic and ultramafic rocks, including fragments of oceanic crust. Chondrite-normalized REE patterns of metasedimentary rocks are characterized by LREE enrichment and lack of an Eu anomaly, similar to REE patterns of co-occurring metabasalts. High MgO concentrations, high Cr/V and low Y/Ni and Th/Sc ratios imply the involvement of ultramafic rocks in the source area, which is also supported by whole-rock Pb isotope data. A geodynamic evolution is envisaged, from an extensional tectonic setting between 1.48–1.43 Ga (rift or retroarc basin) into a compressional, retroarc foreland basin at ca. 1.25–1.20 Ga, the latter being probably related to the Kibaran Orogeny in the Namaqua-Natal Belt. It is proposed that the corresponding arc granites and high-grade metamorphic rocks are likely to be found in one of the several terranes in the Namaqua sector of the belt. The Apiaí Terrane (Ribeira Belt, Brazil) shows a similar geological record and evolution as the NPT, and maybe a fragment of the latter displaced to the NW by the Ibaré Shear Zone. The Tapes Complex is a key unit for understanding the assembly of the Río de la Plata and Kalahari cratons, and their incorporation into the Rodinia supercontinent.Fil: Gaucher, Claudio. Universidad de la República; UruguayFil: Frei, Robert. Universidad de Copenhagen; DinamarcaFil: Samaniego, Lucía. Centro Regional para la Gestión de Aguas Subterráneas; Uruguay. Universidad de la República; UruguayFil: Will, Thomas M.. Universität Würzburg; AlemaniaFil: Chemale, Farid. Universidad de Vale do Rio dos Sinos; BrasilFil: Gargiulo, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Geológico del Sur. Universidad Nacional del Sur. Departamento de Geología. Instituto Geológico del Sur; ArgentinaFil: Poire, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Ling, Xiaoxiao. Chinese Academy of Sciences. Institute of Geology and Geophysics. State Key Laboratory of Lithospheric Evolution; ChinaFil: Li, Xian Hua. Chinese Academy of Sciences. Institute of Geology and Geophysics. State Key Laboratory of Lithospheric Evolution; ChinaFil: Li, Qiu Li. Universidad de Copenhagen; Dinamarc

Deposition potential of 0.003-10 mu m ambient particles in the humidified human respiratory tract : Contribution of new particle formation events in Beijing

Ultrafine particles (UFPs) usually explosive growth during new particle formation (NPF) events. However, the risk of exposure to UFPs on NPF days has been ignored due to the prevalence of mass-based air quality standards. In this study, the daily deposited doses, i.e., the daily deposited particle number dose (D-PNd), mass dose (D-PMd), and surface area dose (D-PSd), of ambient particles in the human respiratory tract in Beijing were evaluated based on the particle number size distribution (3 nm-10 mu m) from June 2018 to May 2019 utilizing a Multiple-Path Particle Dosimetry Model (MPPD) after the hygroscopic growth of particles in the respiratory tract had been accounted for. Our observations showed a high frequency (72.6%) of NPF on excellent air quality days, with daily mean PM2.5 concentrations less than 35 mu g m(-3). The daily D-PNd on excellent air quality days was com-parable with that on polluted days, although the D-PMd on excellent air quality days was as low as 15.6% of that on polluted days. The D-PNd on NPF days was similar to 1.3 times that on non-NPF days. The D-PNd in respiratory tract regions decreased in the order: tracheobronchial (TB) > pulmonary (PUL) > extrathoracic (ET) on NPF days, while it was PUL > TB > ET on non-NPF days. The number of deposited nucleation mode particles, which were deposited mainly in the TB region (45%), was 2 times higher on NPF days than that on non-NPF days. Our results demonstrated that the deposition potential due to UFPs in terms of particle number concentrations is high in Beijing regardless of the aerosol mass concentration. More toxicological studies related to UFPs on NPF days, especially those targeting tracheobronchial and pulmonary impairment, are required in the future.Peer reviewe