The degeneration and destruction of femoral articular cartilage shows a greater degree of deterioration than that of the tibial and patellar articular cartilage in early stage knee osteoarthritis: a cross-sectional study

SummaryObjectiveThe aim of the present study was to examine whether the degenerative and morphological changes of articular cartilage in early stage knee osteoarthritis (OA) occurred equally for both femoral- and tibial- or patellar- articular cartilage using magnetic resonance imaging (MRI)-based analyses.DesignThis cross-sectional study was approved by the ethics committee of our university. Fifty patients with early stage painful knee OA were enrolled. The patients underwent 3.0 T MRI on the affected knee joint. Healthy volunteers who did not show MRI-based OA changes were also recruited as controls (n = 19). The degenerative changes of the articular cartilage were quantified by a T2 mapping analysis, and any structural changes were conducted using Whole Organ Magnetic Resonance Imaging Score (WORMS) technique.ResultsAll patients showed MRI-detected OA morphological changes. The T2 values of femoral condyle (FC) (P < 0.0001) and groove (P = 0.0001) in patients with early stage knee OA were significantly increased in comparison to those in the control, while no significant differences in the T2 values of patellar and tibial plateau (TP) were observed between the patients and the control. The WORMS cartilage and osteophyte scores of the femoral articular cartilage were significantly higher than those in the patellar- (P = 0.001 and P = 0.007, respectively) and tibial- (P = 0.0001 and P < 0.0001, respectively) articular cartilage in the patients with early stage knee OA.ConclusionsThe degradation and destruction of the femoral articular cartilage demonstrated a greater degree of deterioration than those of the tibial- and patellar- articular cartilage in patients with early stage knee OA

Nonrigid chiral soliton for the octet and decuplet baryons

Systematic treatment of the collective rotation of the nonrigid chiral soliton is developed in the SU(3) chiral quark soliton model and applied to the octet and decuplet baryons. The strangeness degrees of freedom are treated by a simplified bound-state approach which omits the locality of the kaon wave function. Then, the flavor rotation is divided into the isospin rotation and the emission and absorption of the kaon. The kaon Hamiltonian is diagonalized by the Hartree approximation. The soliton changes the shape according to the strangeness. The baryons appear as the rotational bands of the combined system of the soliton and the kaon.Comment: 11 pages(LaTex), 1 figures(eps

A prominent β-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation

RecQ helicases have attracted considerable interest in recent years due to their role in the suppression of genome instability and human diseases. These atypical helicases exert their function by resolving a number of highly specific DNA structures. The crystal structure of a truncated catalytic core of the human RECQ1 helicase (RECQ149–616) shows a prominent β-hairpin, with an aromatic residue (Y564) at the tip, located in the C-terminal winged-helix domain. Here, we show that the β-hairpin is required for the DNA unwinding and Holliday junction (HJ) resolution activity of full-length RECQ1, confirming that it represents an important determinant for the distinct substrate specificity of the five human RecQ helicases. In addition, we found that the β-hairpin is required for dimer formation in RECQ149–616 and tetramer formation in full-length RECQ1. We confirmed the presence of stable RECQ149–616 dimers in solution and demonstrated that dimer formation favours DNA unwinding; even though RECQ1 monomers are still active. Tetramers are instead necessary for more specialized activities such as HJ resolution and strand annealing. Interestingly, two independent protein–protein contacts are required for tetramer formation, one involves the β-hairpin and the other the N-terminus of RECQ1, suggesting a non-hierarchical mechanism of tetramer assembly

Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model

Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development

Instability of the hedgehog shape for the octet baryon in the chiral quark soliton model

In this paper the stability of the hedgehog shape of the chiral soliton is studied for the octet baryon with the SU(3) chiral quark soliton model. The strangeness degrees of freedom are treated by a simplified bound-state approach, which omits the locality of the kaon wave function. The mean field approximation for the flavor rotation is applied to the model. The classical soliton changes shape according to the strangeness. The baryon appears as a rotational band of the combined system of the deformed soliton and the kaon.Comment: 24 pages, LaTeX, 8 eps file

Extended Hauser-Feshbach Method for Statistical Binary-Decay of Light-Mass Systems

An Extended Hauser-Feshbach Method (EHFM) is developed for light heavy-ion fusion reactions in order to provide a detailed analysis of all the possible decay channels by including explicitly the fusion-fission phase-space in the description of the cascade chain. The mass-asymmetric fission component is considered as a complex-fragment binary-decay which can be treated in the same way as the light-particle evaporation from the compound nucleus in statistical-model calculations. The method of the phase-space integrations for the binary-decay is an extension of the usual Hauser-Feshbach formalism to be applied to the mass-symmetric fission part. The EHFM calculations include ground-state binding energies and discrete levels in the low excitation-energy regions which are essential for an accurate evaluation of the phase-space integrations of the complex-fragment emission (fission). In the present calculations, EHFM is applied to the first-chance binary-decay by assuming that the second-chance fission decay is negligible. In a similar manner to the description of the fusion-evaporation process, the usual cascade calculation of light-particle emission from the highly excited complex fragments is applied. This complete calculation is then defined as EHFM+CASCADE. Calculated quantities such as charge-, mass- and kinetic-energy distributions are compared with inclusive and/or exclusive data for the $^{32}$S+$^{24}$Mg and $^{35}$Cl+$^{12}$C reactions which have been selected as typical examples. Finally, the missing charge distributions extracted from exclusive measurements are also successfully compared with the EHFM+CASCADE predictions.Comment: 34 pages, 6 Figures available upon request, Phys. Rev. C (to be published

Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers

RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germline RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1 expression has clinicopathologic significance in sporadic breast cancers is unknown. We evaluated RECQL1 at the transcriptomic level (METABRIC cohort, n = 1,977) and at the protein level [cohort 1, n = 897; cohort 2, n = 252; cohort 3 (BRCA germline deficient), n = 74]. In RECQL1-depleted breast cancer cells, we investigated anthracycline sensitivity. High RECQL1 mRNA was associated with intClust.3 (P = 0.026), which is characterized by low genomic instability. On the other hand, low RECQL1 mRNA was linked to intClust.8 [luminal A estrogen receptor–positive (ER+) subgroup; P = 0.0455] and intClust.9 (luminal B ER+ subgroup; P = 0.0346) molecular phenotypes. Low RECQL1 expression was associated with shorter breast cancer–specific survival (P = 0.001). At the protein level, low nuclear RECQL1 level was associated with larger tumor size, lymph node positivity, high tumor grade, high mitotic index, pleomorphism, dedifferentiation, ER negativity, and HER-2 overexpression (P < 0.05). In ER+ tumors that received endocrine therapy, low RECQL1 was associated with poor survival (P = 0.008). However, in ER− tumors that received anthracycline-based chemotherapy, high RECQL1 was associated with poor survival (P = 0.048). In RECQL1-depleted breast cancer cell lines, we confirmed doxorubicin sensitivity, which was associated with DNA double-strand breaks accumulation, S-phase cell-cycle arrest, and apoptosis. We conclude that RECQL1 has prognostic and predictive significance in breast cancers

Long-Lasting Insecticidal Nets Incorporating Piperonyl Butoxide Reduce the Risk of Malaria in Children in Western Kenya: A Cluster Randomized Controlled Trial

Malaria vectors have acquired an enzyme that metabolizes pyrethroids. To tackle this problem, we evaluated long-lasting insecticidal nets incorporating piperonyl butoxide (PBO-LLINs) with a community-based cluster randomized control trial in western Kenya. The primary endpoints were anopheline density and Plasmodium falciparum polymerase chain reaction (PCR)-positive prevalence (PCRpfPR) of children aged 7 months to 10 years. Four clusters were randomly selected for each of the treatment and control arms (eight clusters in total) from 12 clusters, and PBO-LLINs and standard LLINs were distributed in February 2011 to 982 and 1,028 houses for treatment and control arms, respectively. Entomological surveys targeted 20 houses in each cluster, and epidemiological surveys targeted 150 children. Cluster-level permutation tests evaluated the effectiveness using the fitted values from individual level regression models adjusted for baseline. Bootstrapping estimated 95% confidence intervals (CIs). The medians of anophelines per house were 1.4 (interquartile range [IQR]: 2.3) and 3.4 (IQR: 3.7) in the intervention and control arms after 3 months, and 0.4 (IQR: 0.2) and 1.6 (IQR: 0.5) after 10 months, respectively. The differences were –2.5 (95% CI: –6.4 to –0.6) and –1.3 (95% CI: –2.0 to –0.7), respectively. The datasets of 861 and 775 children were analyzed in two epidemiological surveys. The median PCRpfPRs were 25% (IQR: 11%) in the intervention arm and 52% (IQR: 11%) in the control arm after 5 months and 33% (IQR: 11%) and 45% (IQR: 5%) after 12 months. The PCRpfPR ratios were 0.67 (95% CI: 0.38, 0.91) and 0.74 (95% CI: 0.53, 0.90), respectively. We confirmed the superiority of PBO-LLINs