Revealing the molecular signatures of host-pathogen interactions.

Advances in sequencing technology and genome-wide association studies are now revealing the complex interactions between hosts and pathogen through genomic variation signatures, which arise from evolutionary co-existence

Could salvage surgery after chemotherapy have clinical impact on cancer survival of patients with metastatic urothelial carcinoma?

The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy. Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery. All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test). Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival

Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema

BACKGROUND: Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. METHODS: We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. RESULTS: In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 ± 2.7 ms versus 53.9 ± 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema. CONCLUSION: This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans

KAGRA: 2.5 Generation Interferometric Gravitational Wave Detector

The recent detections of gravitational waves (GWs) reported by LIGO/Virgocollaborations have made significant impact on physics and astronomy. A globalnetwork of GW detectors will play a key role to solve the unknown nature of thesources in coordinated observations with astronomical telescopes and detectors.Here we introduce KAGRA (former name LCGT; Large-scale Cryogenic Gravitationalwave Telescope), a new GW detector with two 3-km baseline arms arranged in theshape of an "L", located inside the Mt. Ikenoyama, Kamioka, Gifu, Japan.KAGRA's design is similar to those of the second generations such as AdvancedLIGO/Virgo, but it will be operating at the cryogenic temperature with sapphiremirrors. This low temperature feature is advantageous for improving thesensitivity around 100 Hz and is considered as an important feature for thethird generation GW detector concept (e.g. Einstein Telescope of Europe orCosmic Explorer of USA). Hence, KAGRA is often called as a 2.5 generation GWdetector based on laser interferometry. The installation and commissioning ofKAGRA is underway and its cryogenic systems have been successfully tested inMay, 2018. KAGRA's first observation run is scheduled in late 2019, aiming tojoin the third observation run (O3) of the advanced LIGO/Virgo network. In thiswork, we describe a brief history of KAGRA and highlights of main feature. Wealso discuss the prospects of GW observation with KAGRA in the era of O3. Whenoperating along with the existing GW detectors, KAGRA will be helpful to locatea GW source more accurately and to determine the source parameters with higherprecision, providing information for follow-up observations of a GW triggercandidate

Molecular and phylogenetic analysis of HIV-1 variants circulating in Italy

<p>Abstract</p> <p>Objective</p> <p>The continuous identification of HIV-1 non-B subtypes and recombinant forms in Italy indicates the need of constant molecular epidemiology survey of genetic forms circulating and transmitted in the resident population.</p> <p>Methods</p> <p>The distribution of HIV-1 subtypes has been evaluated in 25 seropositive individuals residing in Italy, most of whom were infected through a sexual route during the 1995–2005 period. Each sample has been characterized by detailed molecular and phylogenetic analyses.</p> <p>Results</p> <p>18 of the 25 samples were positive at HIV-1 PCR amplification. Three samples showed a nucleotide divergence compatible with a non-B subtype classification. The phylogenetic analysis, performed on both HIV-1 <it>env </it>and <it>gag </it>regions, confirms the molecular sub-typing prediction, given that 1 sample falls into the C subtype and 2 into the G subtype. The B subtype isolates show high levels of <it>intra</it>-subtype nucleotide divergence, compatible with a long-lasting epidemic and a progressive HIV-1 molecular diversification.</p> <p>Conclusion</p> <p>The Italian HIV-1 epidemic is still mostly attributable to the B subtype, regardless the transmission route, which shows an increasing nucleotide heterogeneity. Heterosexual transmission and the interracial blending, however, are slowly introducing novel HIV-1 subtypes. Therefore, a molecular monitoring is needed to follow the constant evolution of the HIV-1 epidemic.</p

Application of independent component analysis to the iKAGRA data

We apply independent component analysis (ICA) to real data from a gravitational wave detector for the first time. Specifically, we use the iKAGRA data taken in April 2016, and calculate the correlations between the gravitational wave strain channel and 35 physical environmental channels. Using a couple of seismic channels which are found to be strongly correlated with the strain, we perform ICA. Injecting a sinusoidal continuous signal in the strain channel, we find that ICA recovers correct parameters with enhanced signal-to-noise ratio, which demonstrates the usefulness of this method. Among the two implementations of ICA used here, we find the correlation method yields the optimal results for the case of environmental noise acting on the strain channel linearly