Inferring gene regulatory networks from asynchronous microarray data with AIRnet

Background Modern approaches to treating genetic disorders, cancers and even epidemics rely on a detailed understanding of the underlying gene signaling network. Previous work has used time series microarray data to infer gene signaling networks given a large number of accurate time series samples. Microarray data available for many biological experiments is limited to a small number of arrays with little or no time series guarantees. When several samples are averaged to examine differences in mean value between a diseased and normal state, information from individual samples that could indicate a gene relationship can be lost. Results Asynchronous Inference of Regulatory Networks (AIRnet) provides gene signaling network inference using more practical assumptions about the microarray data. By learning correlation patterns for the changes in microarray values from all pairs of samples, accurate network reconstructions can be performed with data that is normally available in microarray experiments. Conclusions By focussing on the changes between microarray samples, instead of absolute values, increased information can be gleaned from expression data

Improved Breath Phase and Continuous Adventitious Sound Detection in Lung and Tracheal Sound Using Mixed Set Training and Domain Adaptation

Previously, we established a lung sound database, HF_Lung_V2 and proposed convolutional bidirectional gated recurrent unit (CNN-BiGRU) models with adequate ability for inhalation, exhalation, continuous adventitious sound (CAS), and discontinuous adventitious sound detection in the lung sound. In this study, we proceeded to build a tracheal sound database, HF_Tracheal_V1, containing 11107 of 15-second tracheal sound recordings, 23087 inhalation labels, 16728 exhalation labels, and 6874 CAS labels. The tracheal sound in HF_Tracheal_V1 and the lung sound in HF_Lung_V2 were either combined or used alone to train the CNN-BiGRU models for respective lung and tracheal sound analysis. Different training strategies were investigated and compared: (1) using full training (training from scratch) to train the lung sound models using lung sound alone and train the tracheal sound models using tracheal sound alone, (2) using a mixed set that contains both the lung and tracheal sound to train the models, and (3) using domain adaptation that finetuned the pre-trained lung sound models with the tracheal sound data and vice versa. Results showed that the models trained only by lung sound performed poorly in the tracheal sound analysis and vice versa. However, the mixed set training and domain adaptation can improve the performance of exhalation and CAS detection in the lung sound, and inhalation, exhalation, and CAS detection in the tracheal sound compared to positive controls (lung models trained only by lung sound and vice versa). Especially, a model derived from the mixed set training prevails in the situation of killing two birds with one stone.Comment: To be submitted, 31 pages, 6 figures, 5 table

The osteoprotective effect of Herba epimedii (HEP) extract in vivo and in vitro

Herba epimedii (HEP) is one of the most frequently used herbs prescribed for treatment of osteoporosis in China. In the present study, the in vivo effects of HEP extract on bone metabolism were evaluated using 4-month-old ovariectomized (OVX) or sham-operated (Sham) female Sprague-Dawley rats orally administered with HEP extract (110 mg kg(−1)d(−1)), 17ß-estrogen (2 mg kg(−1)d(−1)) or its vehicle for 3 months. HEP extract significantly decreased urinary calcium excretion, suppressed serum alkaline phosphatase (ALP) activity and urinary deoxypyridinoline levels in OVX rats (P < 0.05 versus vehicle-treated OVX rats). Histomorphometric analysis indicated that HEP extract could prevent OVX-induced bone loss by increasing tibial trabecular bone area and decreasing trabecular separation in OVX rats (P < 0.05 versus vehicle-treated OVX group). The in vitro effects of HEP extract were also studied using rat osteoblast-like UMR 106 cells. HEP extract significantly stimulated cell proliferation in a dose-dependent manner (P < 0.01 versus vehicle-treated) and increased ALP activity at 200 μgml(−1) (P < 0.01 versus vehicle-treated) in UMR 106 cells. It modulated osteoclastogenesis by increasing osteoprotegrin (OPG) mRNA and decreasing receptor activator of NF-κB ligand (RANKL) mRNA expression, resulting in a dose-dependent increase in OPG/RANKL mRNA ratio (P < 0.01 versus vehicle-treated). Taken together, HEP treatment can effectively suppress the OVX-induced increase in bone turnover possibly by both an increase in osteoblastic activities and a decrease in osteoclastogenesis. The present study provides the evidence that HEP can be considered as a complementary and alternative medicine for treatment of post-menopausal osteoporosis

A Novel Design of Grooved Fibers for Fiber-Optic Localized Plasmon Resonance Biosensors

Bio-molecular recognition is detected by the unique optical properties of self-assembled gold nanoparticles on the unclad portions of an optical fiber whose surfaces have been modified with a receptor. To enhance the performance of the sensing platform, the sensing element is integrated with a microfluidic chip to reduce sample and reagent volume, to shorten response time and analysis time, as well as to increase sensitivity. The main purpose of the present study is to design grooves on the optical fiber for the FO-LPR microfluidic chip and investigate the effect of the groove geometry on the biochemical binding kinetics through simulations. The optical fiber is designed and termed as U-type or D-type based on the shape of the grooves. The numerical results indicate that the design of the D-type fiber exhibits efficient performance on biochemical binding. The grooves designed on the optical fiber also induce chaotic advection to enhance the mixing in the microchannel. The mixing patterns indicate that D-type grooves enhance the mixing more effectively than U-type grooves. D-type fiber with six grooves is the optimum design according to the numerical results. The experimental results show that the D-type fiber could sustain larger elongation than the U-type fiber. Furthermore, this study successfully demonstrates the feasibility of fabricating the grooved optical fibers by the femtosecond laser, and making a transmission-based FO-LPR probe for chemical sensing. The sensor resolution of the sensor implementing the D-type fiber modified by gold nanoparticles was 4.1 × 10−7 RIU, which is much more sensitive than that of U-type optical fiber (1.8 × 10−3 RIU)

Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection.

Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 × 10(-5)). Compared to HBV patients with higher mtDNA content, those with lower mtDNA content had a significantly increased risk of HCC with an odds ratio (OR) of 2.19 (95% confidence interval [CI] 1.28-3.72, P = 0.004). Quartile analyses revealed a significant dose-dependent effect (Ptrend = 0.001) for this association. In a pilot longitudinal sub-cohort of 14 matched cases-control pairs, we observed a trend of dramatically decreased mtDNA content in cases and slightly decreased mtDNA content in controls, with a significant interaction of case-control status with time (Pinteraction = 0.049). Our findings suggest that circulating mtDNA is a potential novel non-invasive biomarker of HCC risk in HBV patients

Benchmarking of eight recurrent neural network variants for breath phase and adventitious sound detection on a self-developed open-access lung sound database-HF_Lung_V1

A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchi labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests for long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.Comment: 48 pages, 8 figures. To be submitte

Phosducin-like protein 1 is essential for G-protein assembly and signaling in retinal rod photoreceptors

G protein β subunits perform essential neuronal functions as part of G protein βγ and Gβ(5)-RGS (Regulators of G protein Signaling) complexes. Both Gβγ and Gβ(5)-RGS are obligate dimers that are thought to require the assistance of the cytosolic chaperonin CCT and a co-chaperone, phosducin-like protein 1 (PhLP1) for dimer formation. To test this hypothesis in vivo, we deleted the Phlp1 gene in mouse (Mus musculus) retinal rod photoreceptor cells and measured the effects on G protein biogenesis and visual signal transduction. In the PhLP1-depleted rods, Gβγ dimer formation was decreased 50-fold, resulting in a more than 10-fold decrease in light sensitivity. Moreover, a 20-fold reduction in Gβ(5) and RGS9-1 expression was also observed, causing a 15-fold delay in the shutoff of light responses. These findings conclusively demonstrate in vivo that PhLP1 is required for the folding and assembly of both Gβγ and Gβ(5)-RGS9

Methane dynamics in an estuarine brackish Cyperus malaccensis marsh: Production and porewater concentration in soils, and net emissions to the atmosphere over five years

Wetlands can potentially affect global climate change through their role in modulating the atmospheric concentrations of methane (CH4). Their overall CH4 emissions, however, remain the greatest uncertainty in the global CH4 budget. One reason for this is the paucity of long-term field measurements to characterize the variability of CH4 emissions from different types of wetlands. In this study, we quantified CH4 emissions from a brackish, oligohaline Cyperus malaccensis marsh ecosystem in the Min River Estuary in southeast China over five years. Our results showed substantial temporal variability of CH4 emissions from this brackish marsh, with hourly fluxes ranging from 0.7 ± 0.6 to 5.1 ± 3.7 mg m−2 h−1 (mean ± 1 SD) during the study period. The inter-annual variability of CH4 emissions was significantly correlated with changes in soil temperature, precipitation and salinity, which highlighted the importance of long-term observations in understanding wetland CH4 dynamics. Distinct seasonal patterns in soil CH4 production rates and porewater CH4 concentrations also were observed, and were both positively correlated with CH4 emissions. The seasonal variations of CH4 emissions and production were highly correlated with salinity and porewater sulfate levels. The mean annual CH4 efflux from our site over the five-year period was 23.8 ± 18.1 g CH4 m−2 yr−1, indicating that subtropical brackish tidal marsh ecosystems could release a large amount of CH4 into the atmosphere. Our findings further highlight the need to obtain high-frequency and continuous field measurements over the long term at multiple spatial scales to improve our current estimates of wetland CH4 emissions

A Sampling Train for Rapid Measurement of Regional Lung Deposition

ABSTRACT An experimental system for rapid measurement of regional lung deposition of Di-2-ethylhexyl sebacate (DEHS) aerosol particles was established in the present study. The principal goal was to identify the most relevant components of the sampling train and the proper instruments to be employed. After completing the search for an optimal sampling train and instruments, a human subject test was performed. Overall, the sampling train consisted of a mouthpiece, flow meter, and particle counter. The mouthpiece was attached to a Fleisch pneumotachograph. Several TSI condensation particle counters (CPCs), a PC-LabCard and a personal computer were employed to measure and record the counts of test particles at 100 Hz. A cylinder-piston breathing machine was built to generate a series of &quot;standard&quot; breathing patterns. For non-human subject tests, an acrylic tube, 5 cm diameter × 60 cm length, packed with a piece of 100 ppi foam disks was used as a substitute for the human respiratory tract. The optimal sampling train was determined to be a 1TH Fleisch pneumotachograph with a CPC model 3025A because of its short response time and low flow fluctuation. A healthy non-smoking man volunteered to be the subject, and was asked to follow breathing patterns generated by a cylinder-piston breathing machine. The local deposition efficiency was calculated for 1 μm DEHS particles of each 50 cm 3 volumetric region. The deposition data showed a good agreement with previous studies. Compared to the conventional bolus system, the advantage of the rapid measurement system developed in this work is its simplicity, low exposure, and high efficiency