A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

Our goal is to develop a rapid and scalable system for functionally evaluating deregulated genes in multiple myeloma (MM). Here, we forcibly expressed human cMYC and KRAS12V in mouse T2 B cells (IgM+B220+CD38+IgD+) using retroviral transduction and transplanted these cells into lethally irradiated recipient mice. Recipients developed plasmacytomas with short onset (70 days) and high penetrance, whereas neither cMYC nor KRAS12V alone induced disease in recipient mice. Tumor cell morphology and cell surface biomarkers (CD138+B220−IgM−GFP+) indicate a plasma cell neoplasm. Gene set enrichment analysis further confirms that the tumor cells have a plasma cell gene expression signature. Plasmacytoma cells infiltrated multiple loci in the bone marrow, spleen and liver; secreted immunoglobulins; and caused glomerular damage. Our findings therefore demonstrate that deregulated expression of cMYC with KRAS12V in T2 B cells rapidly generates a plasma cell disease in mice, suggesting utility of this model both to elucidate molecular pathogenesis and to validate novel targeted therapies

Giant shift upon strain on the fluorescence spectrum of VNNB color centers in h-BN

We study the effect of strain on the physical properties of the nitrogen antisite-vacancy pair in hexagonal boron nitride ($h$-BN), a color center that may be employed as a quantum bit in a two-dimensional material. With group theory and ab-initio analysis we show that strong electron-phonon coupling plays a key role in the optical activation of this color center. We find a giant shift on the zero-phonon-line (ZPL) emission of the nitrogen antisite-vacancy pair defect upon applying strain that is typical of $h$-BN samples. Our results provide a plausible explanation for the experimental observation of quantum emitters with similar optical properties but widely scattered ZPL wavelengths and the experimentally observed dependence of the ZPL on the strain.Comment: 7 pages, 3 figure

A Multi-Center Study to Evaluate the Performance of Phage Amplified Biologically Assay for Detecting TB in Sputum in the Pulmonary TB Patients

Objective: To evaluate the performance of phage amplified biologically assay (PhaB) for detecting tuberculosis (TB) in sputum in the pulmonary tuberculosis (PTB) patients. Methods: Shanghai Tuberculosis Key Laboratory of Shanghai Pulmonary Hospital participated in the project in collaboration with the laboratories of six hospitals and a total of 1660 eligible participants (1351 PTB patients and 309 non-TB patients) were included in the study. The sputum samples from the participants were detected by smear microscopy, PhaB, and Löwenstein-Jensen (L-J) culture method, respectively. Results: The overall sensitivity of PhaB were higher than that of L-J culture and smear microscopy (p,0.05). The sensitivity of PhaB for detecting smear-negative specimens was obviously higher than that of L-J culture (p,0.05). Compared with L-J culture, the overall sensitivity, specificity, PPV, NPV, ACC and Kappa value of PhaB were 98.4 (95 % Cl: 96.9–99.3), 71.6 (95% Cl: 68.4–74.6), 67.7, 98.7, 81.7 % and 0.643, respectively. The detection median time of PhaB only needed 48 hours, which was significantly less than that (31 days) of L-J culture method. Conclusion: PhaB method is a rapid and sensitive method for detecting TB in sputum in PTB patients; especially for th

A gallotannin-rich fraction from Caesalpinia spinosa (Molina) Kuntze displays cytotoxic activity and raises sensitivity to doxorubicin in a leukemia cell line

<p>Abstract</p> <p>Background</p> <p>Enhancement of tumor cell sensitivity may help facilitate a reduction in drug dosage using conventional chemotherapies. Consequently, it is worthwhile to search for adjuvants with the potential of increasing chemotherapeutic drug effectiveness and improving patient quality of life. Natural products are a very good source of such adjuvants.</p> <p>Methods</p> <p>The biological activity of a fraction enriched in hydrolysable polyphenols (P2Et) obtained from <it>Caesalpinia spinosa </it>was evaluated using the hematopoietic cell line K562. This fraction was tested alone or in combination with the conventional chemotherapeutic drugs doxorubicin, vincristine, etoposide, camptothecin and taxol. The parameters evaluated were mitochondrial depolarization, caspase 3 activation, chromatin condensation and clonogenic activity.</p> <p>Results</p> <p>We found that the P2Et fraction induced mitochondrial depolarization, activated caspase 3, induced chromatin condensation and decreased the clonogenic capacity of the K562 cell line. When the P2Et fraction was used in combination with chemotherapeutic drugs at sub-lethal concentrations, a fourfold reduction in doxorubicin inhibitory concentration 50 (IC₅₀) was seen in the K562 cell line. This finding suggested that P2Et fraction activity is specific for the molecular target of doxorubicin.</p> <p>Conclusions</p> <p>Our results suggest that a natural fraction extracted from <it>Caesalpinia spinosa </it>in combination with conventional chemotherapy in combination with natural products on leukemia cells may increase therapeutic effectiveness in relation to leukemia.</p

The predominance of Human Immunodeficiency Virus type 1 (HIV-1) circulating recombinant form 02 (CRF02_AG) in West Central Africa may be related to its replicative fitness

BACKGROUND: CRF02_AG is the predominant HIV strain circulating in West and West Central Africa. The aim of this study was to test whether this predominance is associated with a higher in vitro replicative fitness relative to parental subtype A and G viruses. Primary HIV-1 isolates (10 CRF02_AG, 5 subtype A and 5 subtype G) were obtained from a well-described Cameroonian cohort. Growth competition experiments were carried out at equal multiplicity of infection in activated T cells and monocyte-derived dendritic cells (MO-DC) in parallel. RESULTS: Dual infection/competition experiments in activated T cells clearly indicated that CRF02_AG isolates had a significant replication advantage over the subtype A and subtype G viruses. The higher fitness of CRF02_AG was evident for isolates from patients with CD4+ T cell counts >200 cells/μL (non-AIDS) or CD4+ T cell counts <200 cells/μL (AIDS), and was independent of the co-receptor tropism. In MO-DC cultures, CRF02_AG isolates showed a slightly but not significantly higher replication advantage compared to subtype A or G isolates. CONCLUSION: We observed a higher ex vivo replicative fitness of CRF02_AG isolates compared to subtype A and G viruses from the same geographic region and showed that this was independent of the co-receptor tropism and irrespective of high or low CD4+ T cell count. This advantage in replicative fitness may contribute to the dominant spread of CRF02_AG over A and G subtypes in West and West Central Africa

A clinicopathological study of Dermatofibrosarcoma Protuberans in Maiduguri, Northeastern Nigeria

Background Dermatofibrosarcoma protuberans (dfsp) is a rare tumour originating from the dermis, it is slow growing, nodular, polypoid neoplasm that invade the subcutaneous tissue and does not usually  metastasis.Clinical presentation is not uniform and may mimic common tropical benign skin lesions.We intend to study the behaviour of this tumour in our environment .Materails and method. A Clinicopathologic study of 36 cases of histologically diagnosed Dermatofibrosarcoma protuberans in University Maiduguri Teaching Hospital was carried out.DFSP constitutes 3.05% of all cases of all cancers and 10.2 % of all skin cancers. The peak age incidence was the 4th and 6th decades with a median age 37.6 years. The males to female ratio was 2:1. The commonest site was the trunk 17(48.8%), followed by the lower limbs 8 (22.9%); upper limbs 6(17.1%); head and neck 3(8.6%) and buttock 1(2.9%) were not frequently affected..Conclsusion: DFSP is a common lesion in our environment that warrants proper clinical assessment, and histological characterisation