Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

Analysis of the changes of electron transfer and heterogeneity of photosystem II in Deg1-reduced Arabidopsis plants.

Deg1 protease functions in protease and chaperone of PSII complex components, but few works were performed to study the effects of Deg1 on electron transport activities on the donor and acceptor side of PSII and its correlation with the photoprotection of PSII during photoinhibition. Therefore, we performed systematic and comprehensive investigations of electron transfers on the donor and acceptor sides of photosystem II (PSII) in the Deg1-reduced transgenic lines deg1-2 and deg1-4. Both the maximal quantum efficiency of PSII photochemistry (Fv/Fm) and the actual PSII efficiency (ΦPSII) decreased significantly in the transgenic plants. Increases in nonphotochemical quenching (NPQ) and the dissipated energy flux per reaction center (DI0/RC) were also shown in the transgenic plants. Along with the decreased D1, CP47, and CP43 content, these results suggested photoinhibition under growth light conditions in transgenic plants. Decreased Deg1 caused inhibition of electron transfer on the PSII reducing side, leading to a decline in the number of QB-reducing centers and accumulation of QB-nonreducing centers. The Tm of the Q band shifted from 5.7 °C in the wild-type plant to 10.4 °C and 14.2 °C in the deg1-2 and deg1-4 plants, respectively, indicating an increase in the stability of S2QA¯ in transgenic plants. PSIIα in the transgenic plants largely reduced, while PSIIß and PSIIγ increased with the decline in the Deg1 levels in transgenic plants suggesting PSIIα centers gradually converted into PSIIß and PSIIγ centers in the transgenic plants. Besides, the connectivity of PSIIα and PSIIß was downregulated in transgenic plants. Our results reveal that downregulation of Deg1 protein levels induced photoinhibition in transgenic plants, leading to loss of PSII activities on both the donor and acceptor sides in transgenic plants. These results give a new insight into the regulation role of Deg1 in PSII electron transport.

Compact U

We propose a bosonic U^{κ}(1) rotor model on a three dimensional spacetime lattice. With the inclusion of a Maxwell term, we show that the low-energy properties of our model can be obtained reliably via a semiclassical approach. Those properties are the same as that of the Chern-Simons field theory, S=∫d^{3}x(K_{IJ}/4π)A_{I}dA_{J}. We require the lattice variables on each link to be compact (i.e., take values on circles), which enforces the quantization of the K matrix as a symmetric integer matrix with even diagonals. Our lattice model also has exact 1-symmetries, which gives rise to the 1-form symmetry in the Chern-Simons field theory. In particular, some of those 1-symmetries are anomalous (i.e., non-on-site) in the expected way. The anomaly can be probed via the breaking of those lattice 1-symmetries by the boundaries.

A novel self-supported porous ZnO nanobelt arrays on Zn foils: excellent binder-free anode materials for LIBs.

ZnO is considered to be one of the promising anode materials for lithium-ion batteries (LIBs), but the poor electronic conductivity and large volume variation during lithium-ion extraction and insertion process of ZnO seriously hinders its commercial application in LIBs. In this study, we synthesized a novel self-supporting porous ZnO nanobelt (PZB) arrays on Zn foils, in which Zn foils can be directly used as current collectors to promote electrically connection between the active materials and the current collectors. Furthermore, the well-aligned ZnO nanobelts have a thin thickness and uniform porous structure, which endue it well improved electrochemical performance. The PZB anodes display a high areal capacity of 5.91 mAh cm-2at current density of 0.5 mA cm-2at room temperature, and deliver an areal capacity of 1.73 mAh cm-2at -20 °C, indicating its excellent application potential especially at low temperatures, and it makes the porous ZnO nanobelts a practical anode material for LIBs.

Plastid Deficient 1 Is Essential for the Accumulation of Plastid-Encoded RNA Polymerase Core Subunit ß and Chloroplast Development in Arabidopsis.

Plastid-encoded RNA polymerase (PEP)-dependent transcription is an essential process for chloroplast development and plant growth. It is a complex event that is regulated by numerous nuclear-encoded proteins. In order to elucidate the complex regulation mechanism of PEP activity, identification and characterization of PEP activity regulation factors are needed. Here, we characterize Plastid Deficient 1 (PD1) as a novel regulator for PEP-dependent gene expression and chloroplast development in Arabidopsis. The PD1 gene encodes a protein that is conserved in photoautotrophic organisms. The Arabidopsis pd1 mutant showed albino and seedling-lethal phenotypes. The plastid development in the pd1 mutant was arrested. The PD1 protein localized in the chloroplasts, and it colocalized with nucleoid protein TRXz. RT-quantitative real-time PCR, northern blot, and run-on analyses indicated that the PEP-dependent transcription in the pd1 mutant was dramatically impaired, whereas the nuclear-encoded RNA polymerase-dependent transcription was up-regulated. The yeast two-hybrid assays and coimmunoprecipitation experiments showed that the PD1 protein interacts with PEP core subunit ß (PEP-ß), which has been verified to be essential for chloroplast development. The immunoblot analysis indicated that the accumulation of PEP-ß was barely detected in the pd1 mutant, whereas the accumulation of the other essential components of the PEP complex, such as core subunits α and ß', were not affected in the pd1 mutant. These observations suggested that the PD1 protein is essential for the accumulation of PEP-ß and chloroplast development in Arabidopsis, potentially by direct interaction with PEP-ß.

Expression of Thomsen-Friedenreich Antigen in Colorectal Cancer and Association with Microsatellite Instability.

Microsatellite instability (MSI) is a molecular phenotype due to a deficient DNA mismatch repair (dMMR). In colorectal cancer (CRC), dMMR/MSI is associated with several clinical and histopathological features, influences prognosis, and is a predictive factor of response to therapy. In daily practice, dMMR/MSI profiles are identified by immunohistochemistry and/or multiplex PCR. The Thomsen-Friedenreich (TF) antigen was previously found to be a potential single marker to identify MSI-high gastric cancers. Therefore, in this study, we aimed to disclose a possible association between TF expression and MSI status in CRC. Furthermore, we evaluated the relationship between TF expression and other clinicopathological features, including patient survival. We evaluated the expression of the TF antigen in a cohort of 25 MSI-high and 71 microsatellite stable (MSS) CRCs. No association was observed between the expression of the TF antigen and MSI-high status in CRC. The survival analysis revealed that patients with MSI-high CRC showed improved survival when the TF antigen was expressed. This finding holds promise as it indicates the potential use of the TF antigen as a biomarker of better prognosis in MSI-high CRCs that should be validated in an independent and larger CRC cohort.

PPR-SMR protein SOT1 has RNA endonuclease activity.

Numerous attempts have been made to identify and engineer sequence-specific RNA endonucleases, as these would allow for efficient RNA manipulation. However, no natural RNA endonuclease that recognizes RNA in a sequence-specific manner has been described to date. Here, we report that SUPPRESSOR OF THYLAKOID FORMATION 1 (SOT1), an Arabidopsis pentatricopeptide repeat (PPR) protein with a small MutS-related (SMR) domain, has RNA endonuclease activity. We show that the SMR moiety of SOT1 performs the endonucleolytic maturation of 23S and 4.5S rRNA through the PPR domain, specifically recognizing a 13-nucleotide RNA sequence in the 5' end of the chloroplast 23S-4.5S rRNA precursor. In addition, we successfully engineered the SOT1 protein with altered PPR motifs to recognize and cleave a predicted RNA substrate. Our findings point to SOT1 as an exciting tool for RNA manipulation.

Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present.

Continuous Topological Phase Transition between Two 1D Antiferromagnetic Spin-1 Boson Superfluids with the Same Symmetry.

Spin-1 bosons on a one-dimensional chain, at incommensurate filling with an antiferromagnetic spin interaction between neighboring bosons, may form a spin-1 boson condensed state that contains both a gapless charge and spin excitations. We argue that the spin-1 boson condensed state is unstable, and will become one of two superfluids by opening a spin gap. One superfluid must have a spin-1 ground state on a ring if it contains an odd number of bosons and has no degenerate states at the chain end. The other superfluid has a spin-0 ground state on a ring for any number of bosons and has a spin-1/2 degeneracy at the chain end. The two superfluids have the same symmetry and only differ by a spin-SO(3) symmetry protected topological order. Although Landau theory forbids a continuous phase transition between two phases with the same symmetry, the phase transition between the two superfluids can be generically continuous, which is described by conformal field theory (CFT) su(2)_{2}⊕u(1)_{4}⊕su(2)[over ¯]_{2}⊕u(1)[over ¯]_{4}. Such a CFT has a spin fractionalization: spin-1 excitation can decay into a spin-1/2 right mover and a spin-1/2 left mover. We determine the critical theory by solving the partition function based on emergent symmetries and modular invariance condition of CFTs.

Tetratricopeptide repeat protein Pyg7 is essential for photosystem I assembly by interacting with PsaC in Arabidopsis.

Although progress has been made in determining the structure and understanding the function of photosystem I (PSI), the PSI assembly process remains poorly understood. PsaC is an essential subunit of PSI and participates in the transfer of electrons to ferredoxin. However, how PsaC is assembled during accumulation of the PSI complex is unknown. In the present study, we showed that Pyg7 localized to the stromal thylakoid and associated with the PSI complex. We also showed that Pyg7 interacted with PsaC. Furthermore, we found that the PSI assembly process was blocked following formation of the PsaAB heterodimer in the pyg7 mutant. In addition, the analyses of PSI stability in Pyg7RNAi plants showed that Pyg7 is involved in maintaining the assembled PSI complex under excess-light conditions. Moreover, we demonstrated that decreased Pyg7 content resulted in decreased efficiency of PSI assembly in Pyg7RNAi plants. These findings suggest that the role of Pyg7 in PSI biogenesis has evolved as an essential assembly factor by interacting with PsaC in Arabidopsis, in addition to being a stability factor for PSI as seen in Synechocystis.

Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant syndrome characterised by multigenerational diffuse gastric cancer, and is mainly caused by germline alterations in the CDH1 gene. Currently, endoscopy has limited diagnostic accuracy, and total gastrectomy (TG) is the treatment of choice for asymptomatic CDH1 carriers. In this study, we aimed to obtain a better understanding of HDGC syndrome by exploring the histopathological findings of TG specimens from asymptomatic HDGC patients. A comprehensive literature review was carried out, searching for TGs performed in asymptomatic HDGC patients. Fourteen unpublished cases, analysed in our institution, were also included. The series encompassed 174 CDH1 carriers. Preoperative endoscopic biopsies were positive in 28.3%. A macroscopic lesion was apparent in 11.7% of TGs. Histopathological analysis revealed intraepithelial lesions and/or intramucosal signet ring cell carcinoma in 87.9% of TGs. When we explored the type of protocol used for handling the specimens, we found that microscopic cancer foci were detected in 95.3% of TGs when a total-embedding protocol (assessment of the totality of gastric mucosa) was applied, and only in 62.5% when no specific protocol was used (P < 0.001). Helicobacter pylori infection was found in 23.4% cases. In conclusion, a thorough histopathological examination of gastric mucosa remains the gold standard for detection of cancer foci in HDGC gastrectomy specimens, requiring experienced pathologists for an accurate diagnosis. A better understanding of the natural history of HDGC will enable better clinical management of HDGC patients, particularly regarding the optimal timing for the performance of TG.

1/2(e

We address the question about the origin of the 1/2(e^{2}/h) conductance plateau observed in a recent experiment on an integer quantum Hall (IQH) film covered by a superconducting (SC) film. Since one-dimensional (1D) chiral Majorana fermions on the edge of the above device can give rise to the half quantized plateau, such a plateau is regarded as conclusive evidence for the chiral Majorana fermions. However, in this Letter we give another mechanism for the 1/2(e^{2}/h) conductance plateau. We find the 1/2(e^{2}/h) conductance plateau to be a general feature of a good electric contact between the IQH film and the SC film, and cannot distinguish the existence or the nonexistence of 1D chiral Majorana fermions. We also find that the contact conductance between a superconductor and an IQH edge channel has a non-Ohmic form σ_{SC-Hall}∝V^{2} in the k_{B}T≪eV limit, if the SC and IQH bulks are fully gapped.

Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease.

BACKGROUND AND AIMS: The time course for the development of clinically significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little is known about the progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. Gastroendoscopy often fails to detect early lesions, and risk-reducing/prophylactic total gastrectomy (PTG) is the only curative approach. We present an HDGC family with early-onset disease in which clinical and histologic findings provided insight into the understanding of different HDGC phenotypes. METHODS: The proband was diagnosed at age 18 years with widely invasive, metastatic DGC. CDH1 genetic testing identified a pathogenic, germline CDH1 variant (c.1901C>T, p.Ala634Val). Thirty family members were tested, and 15 CDH1 carriers were identified. RESULTS: Six family members had PTG, with negative preoperative workup. The proband's 14-year-old sister is the youngest patient, reported to date, to have PTG after negative preoperative biopsy sampling. Intramucosal HDGC foci were detected in all PTG specimens (1-33). In contrast to the "indolent" phenotype of these foci, the aggressive DGC from the proband showed pleomorphic cells, absent E-cadherin expression, increased proliferation (Ki-67 index), and activation of oncogenic events (p53, pSrc and pStat3 overexpression). All family members had Helicobacter pylori gastritis. Cag-A-positive strains were detected in all specimens, except in the proband's sister. CONCLUSIONS: HDGC is a heterogeneous disease regarding clinical behavior, endoscopic findings, histopathologic features, and immunophenotypic/molecular profile. The presence of bizarre, pleomorphic cells in endoscopic biopsy specimens is suggestive of advanced disease and should prompt clinical intervention. The involvement of a full multidisciplinary team is essential for the management of these patients.

Alkali-corrosion synthesis and excellent DSSC performance of novel jujube-like hierarchical TiO2 microspheres.

Novel jujube-like hierarchical TiO2 microspheres (HTMs) were synthesized by an alkali-corrosion process of titanium phosphate (Ti2O3(H2PO4)2 · 2H2O) microspheres. The hierarchical titanium phosphate microsphere (HTPM) intermediates consisting of nanoflakes with a thickness of 20 nm were firstly prepared by a facile hydrothermal method. After reacting with diluted NaOH at low temperature and atmospheric pressure, followed by subsequent acid washing and a calcination process, the HTPM intermediates were transformed to TiO2 with the microsphere morphology well retained, while the nanoflakes became porous, and some new nanowires were formed between the nanoflakes. Finally, HTMs consisting of porous nanoflakes and nanowires were obtained. The possible growth mechanisms of HTPMs and HTMs are discussed. The HTMs demonstrate high specific surface area and excellent light-scattering ability. The performance of the dye sensitized solar cells (DSSCs) of the HTMs synthesized under different conditions is studied, and a total conversion efficiency of up to 8.93% was obtained. The improved DSSC performance was attributed to the enhanced dye loading, light-scattering, and charge transporting ability of the HTMs with a unique hierarchical nanostructure.

Glutathione reductase 2 maintains the function of photosystem II in Arabidopsis under excess light.

Glutathione reductase plays a crucial role in the elimination of H(2)O(2) molecules via the ascorbate-glutathione cycle. In this study, we used transgenic Arabidopsis plants with decreased glutathione reductase 2 (GR2) levels to investigate whether this GR2 activity protects the photosynthetic machinery under excess light. The transgenic plants were highly sensitive to excess light and accumulated high levels of H(2)O(2). Photosystem II (PSII) activity was significantly decreased in transgenic plants. Flash-induced fluorescence relaxation and thermoluminescence measurements demonstrated inhibition of electron transfer between Q(A) and Q(B) and decreased redox potential of Q(B) in transgenic plants. Immunoblot and blue native gel analysis showed that the levels of PSII proteins and PSII complexes were decreased in transgenic plants. Analyses of the repair of photodamaged PSII and in vivo pulse labeling of thylakoid proteins showed that the repair of photodamaged PSII is inhibited due to the inhibition of the synthesis of the D1 protein de novo in transgenic plants. Taken together, our results suggest that under excess light conditions, GR2 plays an important role in maintaining both the function of the acceptor side of PSII and the repair of photodamaged PSII by preventing the accumulation of H(2)O(2). In addition, our results provide details of the role of H(2)O(2) in vivo accumulation in photoinhibition in plants.

Hierarchy Construction and Non-Abelian Families of Generic Topological Orders.

We generalize the hierarchy construction to generic 2+1D topological orders (which can be non-Abelian) by condensing Abelian anyons in one topological order to construct a new one. We show that such construction is reversible and leads to a new equivalence relation between topological orders. We refer to the corresponding equivalence class (the orbit of the hierarchy construction) as "the non-Abelian family." Each non-Abelian family has one or a few root topological orders with the smallest number of anyon types. All the Abelian topological orders belong to the trivial non-Abelian family whose root is the trivial topological order. We show that Abelian anyons in root topological orders must be bosons or fermions with trivial mutual statistics between them. The classification of topological orders is then greatly simplified, by focusing on the roots of each family: those roots are given by non-Abelian modular extensions of representation categories of Abelian groups.

Loop Optimization for Tensor Network Renormalization.

We introduce a tensor renormalization group scheme for coarse graining a two-dimensional tensor network that can be successfully applied to both classical and quantum systems on and off criticality. The key innovation in our scheme is to deform a 2D tensor network into small loops and then optimize the tensors on each loop. In this way, we remove short-range entanglement at each iteration step and significantly improve the accuracy and stability of the renormalization flow. We demonstrate our algorithm in the classical Ising model and a frustrated 2D quantum model.

Helicobacter pylori cagA Promoter Region Sequences Influence CagA Expression and Interleukin 8 Secretion.

Heterogeneity at the Helicobacter pylori cagA gene promoter region has been linked to variation in CagA expression and gastric histopathology. Here, we characterized the cagA promoter and expression in 46 H. pylori strains from Portugal. Our results confirm the relationship between cagA promoter region variation and protein expression originally observed in strains from Colombia. We observed that individuals with intestinal metaplasia were all infected with H. pylori strains containing a specific cagA motif. Additionally, we provided novel functional evidence that strain-specific sequences in the cagA promoter region and CagA expression levels influence interleukin 8 secretion by the host gastric epithelial cells.

Molecular mechanism of photosystem I assembly in oxygenic organisms.

Photosystem I, an integral membrane and multi-subunit complex, catalyzes the oxidation of plastocyanin and the reduction of ferredoxin by absorbed light energy. Photosystem I participates in photosynthetic acclimation processes by being involved in cyclic electron transfer and state transitions for sustaining efficient photosynthesis. The photosystem I complex is highly conserved from cyanobacteria to higher plants and contains the light-harvesting complex and the reaction center complex. The assembly of the photosystem I complex is highly complicated and involves the concerted assembly of multiple subunits and hundreds of cofactors. A suite of regulatory factors for the assembly of photosystem I subunits and cofactors have been identified that constitute an integrative network regulating PSI accumulation. This review aims to discuss recent findings in the field relating to how the photosystem I complex is assembled in oxygenic organisms. This article is part of a Special Issue entitled: Chloroplast Biogenesis.

Enhanced Sucrose Loading Improves Rice Yield by Increasing Grain Size.

Yield in cereals is a function of grain number and size. Sucrose (Suc), the main carbohydrate product of photosynthesis in higher plants, is transported long distances from source leaves to sink organs such as seeds and roots. Here, we report that transgenic rice plants (Oryza sativa) expressing the Arabidopsis (Arabidopsis thaliana) phloem-specific Suc transporter (AtSUC2), which loads Suc into the phloem under control of the phloem protein2 promoter (pPP2), showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. Compared with wild-type plants, pPP2::AtSUC2 plants had larger spikelet hulls and larger and heavier grains. Grain filling was accelerated in the transgenic plants, and more photoassimilate was transported from the leaves to the grain. In addition, microarray analyses revealed that carbohydrate, amino acid, and lipid metabolism was enhanced in the leaves and grain of pPP2::AtSUC2 plants. Thus, enhancing Suc loading represents a promising strategy to improve rice yield to feed the global population.