An Emerging Multidrug-Resistant Pathogen: <em>Streptococcus pneumoniae</em>

Streptococcus pneumoniae (S. pneumoniae) has a multifaceted bond with its human host and causing several diseases in children and adults when host flexible immunity and bacterial acquisition factors allow them to invade essentially sterile spots, such as the middle ear spaces (causes otitis media), lungs (causes pneumonia), bloodstream (causes sepsis) and meninges (causes meningitis). In the early 1940s, management of pneumococcal infections used to be somewhat straightforward, and penicillin commonly was the antibiotic of choice. Soon after mainstreaming antibiotic usage, worldwide emergence of antibiotic resistance among S. pneumoniae isolates has changed this approach. Multiple factors, like prior antibiotic use, inappropriate usage of antibiotics especially in young age, and day care attendance are the most commonly identified risk features for the spread of penicillin resistance and other multiple-antibiotic resistance. Basic fundamental mechanisms of most pneumococcal resistances have been identified, several organizations like WHO, CDC, BSAC, EUCAST started campaigns for appropriate antibiotic use and also the introduction of pneumococcal conjugate vaccines have been recommended to limit the further emergence and spread of pneumococcal resistant

Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking

© 2015 Elsevier Ltd. An adverse in-utero environment is increasingly recognized to predispose to chronic disease in adulthood. Maternal smoking remains the most common modifiable adverse in-utero exposure leading to low birth weight, which is strongly associated with chronic kidney disease (CKD) in later life. In order to investigate underlying mechanisms for such susceptibility, female Balb/c mice were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout gestation and lactation. Offspring kidneys were examined for oxidative stress, expression of mitochondrial proteins, mitochondrial structure as well as renal functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult age). From birth throughout adulthood, SE offspring had increased renal levels of mitochondrial-derived reactive oxygen species (ROS), which left a footprint on DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells. Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week 13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD). Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1-week 13) and lysosome density (day 1 and week 13). The appearance of mitochondrial defects preceded the onset of albuminuria at week 13. Thus, mitochondrial damage caused by maternal smoking may play an important role in development of CKD at adult life

L-carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring

© 2015 the American Physiological Society. Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of L-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I–V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that L-carnitine administration in cigarette smokeexposed mothers mitigates these deleterious renal consequence

Carbonic anhydrase II based biosensing of carbon dioxide at high temperature: an analytical and MD simulation study

Concentration of carbon dioxide (CO2) in the atmosphere has increased significantly due to anthropogenic activities and attributed as a major factor to global warming. Its detection by biosensing methods will provide an alternative for the assessment of CO2 concentration. Biomineralization of CO2 is one of the available methods for the biological conversion of CO2 to carbonate using a highly active enzyme, carbonic anhydrase II (CAII). CAII was used for the carbonation reaction to convert CO2 to CaCO3. The precipitation of calcium carbonate (CaCO3) was promoted in the presence of the CAII at 325 K. CAII showed an enhanced formation of solid CaCO3 through the acceleration of CO2 hydration rate at 325 K. Furthermore, the electrocatalytic properties of glassy carbon electrode enable us to determine the reduction peak potential values of CO2 through cyclic voltammetry at –1.75 and 0.3 V at 325 K. Molecular dynamic (MD) simulations were performed each at 50 ns time scale provided a deeper insight into the molecular basis of the CAII interaction with CO2 at different temperatures, highlighted that the CAII can detect CO2 up to 325 K. We assume that CAII could be an effective and economical biosensor for biomineralization of CO2 at high temperature 325 K

AI-driven blind signature classification for IoT connectivity: a deep learning approach

Non-orthogonal multiple access (NOMA) promises to fulfill the fast-growing connectivities in future Internet of Things (IoT) using abundant multiple-access signatures. While explicitly notifying the utilized NOMA signatures causes large signaling cost, blind signature classification naturally becomes a low-cost option. To accomplish signature classification for NOMA, we study both likelihood- and feature-based methods. A likelihood-based method is firstly proposed and showed to be optimal in the asymptotic limit of the observations, despite high computational complexity. While feature-based classification methods promise low complexity, efficient features are non-trivial to be manually designed. To this end, we resort to artificial intelligence (AI) for deep learning-based automatic feature extraction. Specifically, our proposed deep neural network for signature classification, namely DeepClassifier, establishes on the insights gained from the likelihood-based method, which contains two stages to respectively deal with a single observation and aggregate the classification results of an observation sequence. The first stage utilizes an iterative structure where each layer employs a memory-extended network to explicitly exploit the knowledge of signature pool. The second stage incorporates the straight-through channels within a deep recurrent structure to avoid information loss of previous observations. Experiments show that DeepClassifier approaches the optimal likelihood-based method with a reduction of 90% complexity

Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

BACKGROUND: Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. RESULTS: The linker protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57) of transgenic pigs (F0 generation). CONCLUSIONS: Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species