Miracle-dz/UniFAR-FTUs huggingface dataset:
Negative impact of concurrent overexpression of MYC and BCL2 in patients with advanced diffuse large B-cell lymphoma treated with dose-intensified immunochemotherapy

Abstract Co-expression of MYC and BCL2 proteins in diffuse large B-cell lymphoma (DLBCL), or ‘double-expressor lymphoma’ (DEL), results in poor patient prognosis, but the significance of DEL when aggressive treatments are applied remains uncertain. We performed a retrospective analysis of 40 patients with de novo DLBCL, who were categorized as being at high/high-intermediate risk according to the age-adjusted International Prognostic Index. Patients underwent an R-Double-CHOP regimen, a dose-intensified immunochemotherapy with or without consolidative high-dose chemotherapy followed by autologous stem cell transplantation. According to immunohistochemical analysis, 10 (25%) patients were categorized as having DEL, showing positivity for MYC (≥40%) and BCL2 (≥50%). The 3 year progression-free survival and overall survival of the DEL group were significantly worse compared with those of the non-DEL group (30% vs. 63%, p = 0.019 and 40% vs. 82%, p = 0.006, respectively). These results suggest that advanced DEL may need discrete treatment strategies.
Complete mitochondrial genome sequences of two Indonesian rasboras (Rasbora aprotaenia and Rasbora lateristriata)

Abstract Complete mitochondrial genome sequences were determined for two Indonesian freshwater fishes, Rasbora aprotaenia and Rasbora lateristriata. These genomes are 16,541 bp and 16,539 bp in length, respectively and encode 37 genes in the typical vertebrate gene arrangement. Phylogenetic analyses supported a view that these species are very closely related to each other.
Temperature dependence of needle and shoot elongation before bud break in Scots pine

Knowledge about the early part of needle growth is deficient compared with what is known about shoot growth. It is however important to understand growth of different organs to be able to estimate the changes in whole tree growth in a changing environment. The onset of growth in spring has been observed to occur over some certain threshold value of momentary temperature or temperature accumulation. We measured the length growth of Scots pine (Pinus sylvestris L.) needles and shoots from March until bud break over 3 years. We first compared needle growth with concurrent shoot growth. Then, we quantified threshold temperature of growth (i) with a logistic regression based on momentary temperatures and (ii) with the temperature sum accumulation method. Temperature sum was calculated with combinations of various time steps, starting dates and threshold temperature values. Needle elongation began almost concurrently with shoot elongation and proceeded linearly in relation to shoot growth until bud break. When studying the threshold temperature for growth, the method with momentary temperature effect on growth onset yielded ambiguous results in our conditions. The best fit of an exponential regression between needle growth or length and temperature sum was obtained with threshold temperatures -1 to +2 °C, with several combinations of starting date and time step. We conclude that although growth onset is a momentary event the process leading to it is a long-term continuum where past time temperatures have to be accounted for, rather than a sudden switch from quiescence to active growth. Further, our results indicate that lower temperatures than the commonly used +5 °C are sufficient for actuating the growth process.
Genome-Wide Survey and Expression Analysis of Amino Acid Transporter Gene Family in Rice (Oryza sativa L.)

Background Amino acid transporters (AATs) that transport amino acids across cellular membranes are essential for plant growth and development. To date, a genome-wide overview of the AAT gene family in rice is not yet available. Methodology/Principal Findings In this study, a total of 85 AAT genes were identified in rice genome and were classified into eleven distinct subfamilies based upon their sequence composition and phylogenetic relationship. A large number of OsAAT genes were expanded via gene duplication, 23 and 24 OsAAT genes were tandemly and segmentally duplicated, respectively. Comprehensive analyses were performed to investigate the expression profiles of OsAAT genes in various stages of vegetative and reproductive development by using data from EST, Microarrays, MPSS and Real-time PCR. Many OsAAT genes exhibited abundant and tissue-specific expression patterns. Moreover, 21 OsAAT genes were found to be differentially expressed under the treatments of abiotic stresses. Comparative analysis indicates that 26 AAT genes with close evolutionary relationships between rice and Arabidopsis exhibited similar expression patterns. Conclusions/Significance This study will facilitate further studies on OsAAT family and provide useful clues for functional validation of OsAATs.
Candida albicans Yeast and Hyphae are Discriminated by MAPK Signaling in Vaginal Epithelial Cells

We previously reported that a bi-phasic innate immune MAPK response, constituting activation of the mitogen-activated protein kinase (MAPK) phosphatase MKP1 and c-Fos transcription factor, discriminates between the yeast and hyphal forms of Candida albicans in oral epithelial cells (ECs). Since the vast majority of mucosal Candida infections are vaginal, we sought to determine whether a similar bi-phasic MAPK-based immune response was activated by C. albicans in vaginal ECs. Here, we demonstrate that vaginal ECs orchestrate an innate response to C. albicans via NF-κB and MAPK signaling pathways. However, unlike in oral ECs, the first MAPK response, defined by c-Jun transcription factor activation, is delayed until 2 h in vaginal ECs but is still independent of hypha formation. The ‘second’ or ‘late’ MAPK response, constituting MKP1 and c-Fos transcription factor activation, is identical to oral ECs and is dependent upon both hypha formation and fungal burdens. NF-κB activation is immediate but independent of morphology. Furthermore, the proinflammatory response in vaginal ECs is different to oral ECs, with an absence of G-CSF and CCL20 and low level IL-6 production. Therefore, differences exist in how C. albicans activates signaling mechanisms in oral and vaginal ECs; however, the activation of MAPK-based pathways that discriminate between yeast and hyphal forms is retained between these mucosal sites. We conclude that this MAPK-based signaling pathway is a common mechanism enabling different human epithelial tissues to orchestrate innate immune responses specifically against C. albicans hyphae.
Evaluation of Platelet Indices and Red Cell Distribution Width as New Biomarkers for the Diagnosis of Acute Appendicitis

ABSTRACT Background: Debate around the value of laboratory tests in establishing the diagnosis of acute appendicitis (AA) still continues. This prospective study aimed to investigate the changes in mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW) with the diagnosis of acute appendicitis. Method: 200 patients who underwent emergency appendectomy were included. According to postoperative histology, patients were divided into three groups: acute non-complicated, acute complicated appendicitis (positive appendicectomy groups), and negative appendectomy group. White blood cell (WBC), neutrophil, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelets (PLT) count, MPV, PDW, RDW, and C-reactive protein (CRP) were compared among the groups. Results: One hundred twenty-five (62.5%) patients had non-complicated acute appendicitis, 20 (10%) had complicated acute appendicitis, while 55 (27.5%) had normal appendix. WBC (p <.001), neutrophil (p <.001), NLR (p <.001), PDW (p =.003), and CRP (p =.001) were higher, while lymphocyte (p <.001) and PLT counts (p =.020) were lower in positive appendectomy compared with negative appendectomy patients. MPV levels were insignificantly different across the groups. RDW level was significantly higher in complicated compared with non-complicated acute appendicitis (p =.006); however, no significant difference was found between positive and negative appendectomy groups. Using receiver operating characteristic analysis, sensitivity, specificity, and diagnostic accuracy respectively were 44.83, 100.0, and 72.415% for WBC count, 72.41, 81.82, and 77.115% for neutrophil count, 48.28, 90.91, and 69.595% for PDW, 89.66, 63.64, and 76.65% for CRP. Conclusions: Increased PDW combined with elevated WBC and neutrophil counts maybe used as diagnostic tests in the cases of acute appendicitis, while MPV and RDW levels were not useful diagnostic markers.
Feasibility of combined use of intravascular ultrasound radiofrequency data analysis and optical coherence tomography for detecting thin-cap fibroatheroma

To evaluate the feasibility of the combined use of virtual histology (VH)-intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for detecting in vivo thin-cap ﬁbroatheroma (TCFA). - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Keywords IVUS-derived thin-cap-ﬁberatheroma (TCFA) and optical coherence tomography (OCT) revealed 36 lesions (28.6%) as OCT-derived TCFA. Twenty-eight lesions (22.2%) met the criteria of both IVUS-derived TCFA and OCT-derived TCFA and were diagnosed as deﬁnite-TCFA; 33 lesions were diagnosed as non-thin-cap IVUS-derived TCFA and eight lesions as non-NCCL OCT-derived TCFA.
A Robust and Rapid Method of Producing Soluble, Stable, and Functional G-Protein Coupled Receptors

Membrane proteins, particularly G-protein coupled receptors (GPCRs), are notoriously difficult to express. Using commercial E.coli cell-free systems with the detergent Brij-35, we could rapidly produce milligram quantities of 13 unique GPCRs. Immunoaffinity purification yielded receptors at >90% purity. Secondary structure analysis using circular dichroism indicated that the purified receptors were properly folded. Microscale thermophoresis, a novel label-free and surface-free detection technique that uses thermal gradients, showed that these receptors bound their ligands. The secondary structure and ligand-binding results from cell-free produced proteins were comparable to those expressed and purified from HEK293 cells. Our study demonstrates that cell-free protein production using commercially available kits and optimal detergents is a robust technology that can be used to produce sufficient GPCRs for biochemical, structural, and functional analyses. This robust and simple method may further stimulate others to study the structure and function of membrane proteins.
PB1-F2 Protein Does Not Impact the Virulence of Triple-Reassortant H3N2 Swine Influenza Virus in Pigs but Alters Pathogenicity and Transmission in Turkeys

ABSTRACT PB1-F2 protein, the 11th influenza A virus (IAV) protein, is considered to play an important role in primary influenza virus infection and postinfluenza secondary bacterial pneumonia in mice. The functional role of PB1-F2 has been reported to be a strain-specific and host-specific phenomenon. Its precise contribution to the pathogenicity and transmission of influenza virus in mammalian host, such as swine, and avian hosts, such as turkeys, remain largely unknown. In this study, we explored the role of PB1-F2 protein of triple-reassortant (TR) H3N2 swine influenza virus (SIV) in pigs and turkeys. Using the eight-plasmid reverse genetics system, we rescued wild-type SIV A/swine/Minnesota/1145/2007 (H3N2) (SIV 1145-WT), a PB1-F2 knockout mutant (SIV 1145-KO), and its N66S variant (SIV 1145-N66S). The ablation of PB1-F2 in SIV 1145 modulated early-stage apoptosis but did not affect the viral replication in swine alveolar macrophage cells. In pigs, PB1-F2 expression did not affect nasal shedding, lung viral load, immunophenotypes, and lung pathology. On the other hand, in turkeys, SIV 1145-KO infected poults, and its in-contacts developed clinical signs earlier than SIV 1145-WT groups and also displayed more extensive histopathological changes in intestine. Further, turkeys infected with SIV 1145-N66S displayed poor infectivity and transmissibility. The more extensive histopathologic changes in intestine and relative transmission advantage observed in turkeys infected with SIV 1145-KO need to be further explored. Taken together, these results emphasize the host-specific roles of PB1-F2 in the pathogenicity and transmission of IAV. IMPORTANCE Novel triple-reassortant H3N2 swine influenza virus emerged in 1998 and spread rapidly among the North American swine population. Subsequently, it showed an increased propensity to reassort, generating a range of reassortants. Unlike classical swine influenza virus, TR SIV produces a full-length PB1-F2 protein, which is considered an important virulence marker of IAV pathogenicity. Our study demonstrated that the expression of PB1-F2 does not impact the pathogenicity of TR H3N2 SIV in pigs. On the other hand, deletion of PB1-F2 caused TR H3N2 SIV to induce clinical disease early and resulted in effective transmission among the turkey poults. Our study emphasizes the continuing need to better understand the virulence determinants for IAV in intermediate hosts, such as swine and turkeys, and highlights the host-specific role of PB1-F2 protein.
The Effect of Unerupted Permanent Tooth Crowns on the Distribution of Masticatory Stress in Children

Human mothers wean their children from breast milk at an earlier developmental stage than do ape mothers, resulting in human children chewing solid and semi-solid foods using the deciduous dentition. Mechanical forces generated by chewing solid foods during the post-weaning period travel through not only the deciduous teeth, but also the enamel caps of the developing permanent teeth within the maxilla and mandible, which are not present in the adult face. The effects of mechanical stress propagating through these very stiff structures have yet to be examined. Based on a heuristic model, we predicted that the enamel of the embedded developing teeth would act to reduce stresses in the surrounding bony elements of the juvenile face. We tested this hypothesis by simulating occlusal loading in a finite element (FE) model of a child's cranium with a complete set of deciduous teeth and the first permanent molars embedded in the bony crypt in the maxilla. We modeled bone and enamel with appropriate material properties and assessed the effect of embedding high-stiffness enamel structures on stress distribution in the juvenile face. Against expectation, the presence of unerupted enamel caps does not affect the magnitude or location of stresses in the juvenile face. Our results do not support the hypothesis that the unerupted secondary teeth act to moderate stresses in the juvenile face.
Phytochemical screening and in vitro antimicrobial activity of Bougainvillea spectabilis flower extracts

A b s t r a c t Various flower extracts (Chloroform, ethyl acetate, ethanol and water) of Bougainvillea spectabilis were screened for their phytochemical constituents and also investigated for their antimicrobial activities. Phytochemical screening of flower extracts revealed the presence of alkaloids, flavonoides, phlobatannins and terpenoids. Steroids, phenol, tannins, cardinolides and volatile oils were absent in all the extracts. All flower extracts of B. spectabilis inhibited the growth of few of the bacterial and fungal strains tested with varied effectiveness. The maximum antibacterial activities were observed in ethanol and water extracts. The maximum antifungal activities were observed in chloroform and ethanol extracts. Thus the bioactive natural products in flower extracts of Bougainvillea spectabilis can be used in the development of new pharmaceuticals that address unmet therapeutic use.
/J Mice lpr/lpr Lymphocytes in MRL/MpJ-Fas Accumulation of Activated B and T IL-21 Receptor Is Required for the Systemic

MRL/MpJ-Fas lpr/lpr /J (MRL lpr ) mice develop lupus-like disease manifestations in an IL-21–dependent manner. IL-21 is a pleiotropic cytokine that can inﬂuence the activation, differentiation, and expansion of B and T cell effector subsets. Notably, autoreactive CD4 + Tand B cells spontaneously accumulate in MRL lpr mice and mediate disease pathogenesis. We sought to identify the particular lymphocyte effector subsets regulated by IL-21 in the context of systemic autoimmunity and, thus, generated MRL lpr mice deﬁcient in IL-21R (MRL lpr .IL-21R 2 / 2 ). Lymphadenopathy and splenomegaly, which are characteristic traits of the MRL lpr model were signiﬁcantly reduced in the absence of IL-21R, suggesting that immune activation was likewise decreased. Indeed, spontaneous germinal center formation and plasma cell accumulation were absent in IL-21R–deﬁcient MRL lpr mice. Correspondingly, we observed a signiﬁcant reduction in autoantibody titers. Activated CD4 + CD44 + CD62L lo T cells also failed to accumulate, and CD4 + Th cell differentiation was impaired, as evidenced by a signiﬁcant reduction in CD4 + T cells that produced the pronephritogenic cytokine IFN- g . T extrafollicular helper cells are a recently described subset of activated CD4 + T cells that function as the primary inducers of autoantibody production in MRL lpr mice. Importantly, we demonstrated that T extrafollicular helper cells are dependent on IL-21R for their generation. Together, our data highlighted the novel observation that IL-21 is a critical regulator of multiple pathogenic B and T cell effector subsets in MRL lpr mice. The Journal of Immunology , 2012, 188: 1656–1667. GolgiStop (BD Biosciences) for examined for production of IFN- g , IL-17, and IL-4 by intracellular ﬂow cytometry. Cells were analyzed on a FACSCalibur ﬂow cytometer (BD Biosciences).
NHAR: A non‐homogeneous Arnoldi method for fast simulation of RCL circuits with a large number of ports

Large‐scale RCL circuits with a large number of ports have been widely employed to model interconnect circuits, such as the power/ground networks, clock distribution networks and large data buses in VLSI. The input‐dependent moment‐matching technique, which takes the input excitations into account when constructing the projection matrices for the reduced‐order systems, has been proposed to simulate this type of circuits. The existing input‐dependent moment‐matching methods suffer from either numerical instability in the case of extended Krylov subspace (EKS) and improved extended Krylov subspace (IEKS) methods, or unbearable memory consumption and CPU cost for the EXPanded LINearization (EXPLIN) method. In this paper, a Non‐Homogeneous ARnoldi (NHAR) process, which consists of a memory‐saving and computation‐efficient linearization scheme and a numerical stable partial orthogonalization Arnoldi method, is proposed for the generation of the orthonormal projection matrix. By applying the obtained projection matrix to generate the reduced‐order model, we derive the NHAR method for the model‐order reduction of large‐scale RCL circuits with a large number of ports. The proposed NHAR method can guarantee moment matching, numerical stability and passivity preserving. Compared with the EXPLIN method, NHAR can remarkably reduce the size of the linearized system and therefore can greatly save the memory consumption and computational cost with almost the same accuracy. Moreover, NHAR is numerically stable and can achieve higher accuracy with approximately the same computational cost compared with the EKS and IEKS methods. Copyright © 2009 John Wiley & Sons, Ltd.
Characterization of a New CAMP Factor Carried by an Integrative and Conjugative Element in Streptococcus agalactiae and Spreading in Streptococci

Genetic exchanges between Streptococci occur frequently and contribute to their genome diversification. Most of sequenced streptococcal genomes carry multiple mobile genetic elements including Integrative and Conjugative Elements (ICEs) that play a major role in these horizontal gene transfers. In addition to genes involved in their mobility and regulation, ICEs also carry genes that can confer selective advantages to bacteria. Numerous elements have been described in S. agalactiae especially those integrated at the 3′ end of a tRNALys encoding gene. In strain 515 of S. agalactiae, an invasive neonate human pathogen, the ICE (called 515_tRNALys) is functional and carries different putative virulence genes including one encoding a putative new CAMP factor in addition to the one previously described. This work demonstrated the functionality of this CAMP factor (CAMP factor II) in Lactococcus lactis but also in pathogenic strains of veterinary origin. The search for co-hemolytic factors in a collection of field strains revealed their presence in S. uberis, S. dysgalactiae, but also for the first time in S. equisimilis and S. bovis. Sequencing of these genes revealed the prevalence of a species-specific factor in S. uberis strains (Uberis factor) and the presence of a CAMP factor II encoding gene in S. bovis and S. equisimilis. Furthermore, most of the CAMP factor II positive strains also carried an element integrated in the tRNALys gene. This work thus describes a CAMP factor that is carried by a mobile genetic element and has spread to different streptococcal species.