In Vivo Time-Related Evaluation of a Therapeutic Neutralization Monoclonal Antibody against Lethal Enterovirus 71 Infection in a Mouse Model

Enterovirus 71 (EV71) is a neurotropic virus capable of inducing severe neurological symptoms and death. No direct targeting antivirals are useful in the treatment of severe EV71 infection. Because of low toxicity and good specificity, monoclonal antibodies (MAb) are a potential candidate for the treatment of viral infections. Therefore, we developed an EV71-specific conformational MAb with high in vitro cross-neutralization activity to heterologous EV71 subgenotypes. The in vivo treatment experiment at different days post-infection indicated that a single treatment of MAb CT11F9 within day 3 post-infection fully protected mice from morbidity and mortality (0% PBS vs. 100% at 10 µg/g per body weight ***P<0.0001). Immunohistochemical and histological analysis confirmed that CT11F9 significantly prohibited EV71 VP1 expression in various tissues and prevented EV71-induced myonecrosis. Moreover, thrice-treatment at day 4, 5, 6 post-infection was associated with an increased survival rate (18.2% single vs. 50% thrice at 20 µg/g per body weight), and the mice recovered from limb paralysis. Competitive ELISA also confirmed that CT11F9-recognized epitopes were immunodominant in humans. In conclusion, MAb CT11F9 is an ideal candidate to be humanized and used in severe EV71 infection.     

Integrating Multibeam Backscatter Angular Response,Mosaic and Bathymetry Data for Benthic Habitat Mapping

Multibeam echosounders (MBES) are increasingly becoming the tool of choice for marine habitat mapping applications. In turn, the rapid expansion of habitat mapping studies has resulted in a need for automated classification techniques to efficiently map benthic habitats, assess confidence in model outputs, and evaluate the importance of variables driving the patterns observed. The benthic habitat characterisation process often involves the analysis of MBES bathymetry, backscatter mosaic or angular response with observation data providing ground truth. However, studies that make use of the full range of MBES outputs within a single classification process are limited. We present an approach that integrates backscatter angular response with MBES bathymetry, backscatter mosaic and their derivatives in a classification process using a Random Forests (RF) machine-learning algorithm to predict the distribution of benthic biological habitats. This approach includes a method of deriving statistical features from backscatter angular response curves created from MBES data collated within homogeneous regions of a backscatter mosaic. Using the RF algorithm we assess the relative importance of each variable in order to optimise the classification process and simplify models applied. The results showed that the inclusion of the angular response features in the classification process improved the accuracy of the final habitat maps from 88.5% to 93.6%. The RF algorithm identified bathymetry and the angular response mean as the two most important predictors. However, the highest classification rates were only obtained after incorporating additional features derived from bathymetry and the backscatter mosaic. The angular response features were found to be more important to the classification process compared to the backscatter mosaic features. This analysis indicates that integrating angular response information with bathymetry and the backscatter mosaic, along with their derivatives, constitutes an important improvement for studying the distribution of benthic habitats, which is necessary for effective marine spatial planning and resource management.     

The effect of wearing sanitary napkins of different thicknesses on physiological and psychological responses in Muslim females

Background

Menstruation is associated with significant unpleasantness, and wearing a sanitary napkin (SN) during menses causes discomfort. In addition, many Muslim women use a thick type of SN during menses due to the religious requirement that even disposable SNs be washed before disposal. Therefore, the objective of this study was to measure the physiological and psychological responses to wearing SNs of different thicknesses during menstruation and non-menstruation phases at rest and during physical activity/exercise among Muslim women.

Methods

Eighteen Muslim females were randomly assigned to wear an ultra slim type (US, thin) or a maxi type (MT, thick) SN on two different occasions (i.e., during non-menses and menses). Each subject tested both types of SN. Upon arriving at the laboratory, each subject was equipped with an ambulatory electrocardiograph and rested in a seated position for 10 min. She was then given either an US or MT SN, put it in place, and rested in a seated position for 10 min. Each subject then walked at 3 km/h for 10 min, sat resting for 10 min, and then walked at 5 km/h for another 10 min. At the end of each 10-min stage, subjects marked their feelings of discomfort on the visual analog scale (VAS). Perceived exertion during exercise was evaluated using the Borg scale. Heart rate and low frequency-to-high frequency ratio (LF/HF) of heart rate variability were continuously recorded during rest and exercise.

Results

During both the non-menses and menses trials, VAS and LF/HF were significantly lower in subjects using the US SN compared to the MT SN. These results indicate that when wearing the US SN, subjects were more comfortable and did not increase sympathetic activities. Meanwhile, perceived exertion during exercise had no significant difference between US and MT although the means of the scores for US tended to be lower than those of MT.

Conclusions

The results of this study (VAS and LF/HF) indicate that wearing an US SN induces less physiological and psychological stress compared to wearing a MT SN. Thus, use of the former will empower women to live their lives with vitality during menses.     

Effect of fumarate reducing bacteria on in vitro rumen fermentation,methane mitigation and microbial diversity

The metabolic pathways involved in hydrogen (H₂) production, utilization and the activity of methanogens are the important factors that should be considered in controlling methane (CH₄) emissions by ruminants. H₂ as one of the major substrate for CH₄ production is therefore should be controlled. One of the strategies on reducing CH₄ is through the use of hydrogenotrophic microorganisms such as fumarate reducing bacteria. This study determined the effect of fumarate reducing bacteria, Mitsuokella jalaludinii, supplementation on in vitro rumen fermentation, CH4 production, diversity and quantity. M. jalaludinii significantly reduced CH₄ at 48 and 72 h of incubation and significantly increased succinate at 24 h. Although not significantly different, propionate was found to be highest in treatment containing M. jalaludinii at 12 and 48 h of incubation. These results suggest that supplementation of fumarate reducing bacteria to ruminal fermentation reduces CH₄ production and quantity, increases succinate and changes the rumen microbial diversity.     

A taxonomic study of the genus Panesthia (Blattodea,Blaberidae, Panesthiinae) from China with descriptions of one new species,one new subspecies and the male of Panesthia antennata

One new species Panesthia guizhouensis sp. n. and one new subspecies Panesthia stellata concava ssp. n. are described and illustrated. The male of Panesthia antennata Brunner von Wattenwyl, 1893 and its brachypterous form are described and illustrated for the first time. Panesthia strelkovi Bey-Bienko, 1969 is redescribed and illustrated. Three known species, Panesthia birmanica Brunner von Wattenwyl, 1893, Panesthia sinuata Saussure, 1839 and Panesthia angustipennis cognata Bey-Bienko, 1969 are illustrated. In addition, a key to all species of the genus Panesthia from China is presented.     

Inferring Influenza Infection Attack Rate from Seroprevalence Data

Seroprevalence survey is the most practical method for accurately estimating infection attack rate (IAR) in an epidemic such as influenza. These studies typically entail selecting an arbitrary titer threshold for seropositivity (e.g. microneutralization [MN] 1∶40) and assuming the probability of seropositivity given infection (infection-seropositivity probability, ISP) is 100% or similar to that among clinical cases. We hypothesize that such conventions are not necessarily robust because different thresholds may result in different IAR estimates and serologic responses of clinical cases may not be representative. To illustrate our hypothesis, we used an age-structured transmission model to fully characterize the transmission dynamics and seroprevalence rises of 2009 influenza pandemic A/H1N1 (pdmH1N1) during its first wave in Hong Kong. We estimated that while 99% of pdmH1N1 infections became MN_1∶20 seropositive, only 72%, 62%, 58% and 34% of infections among age 3–12, 13–19, 20–29, 30–59 became MN_1∶40 seropositive, which was much lower than the 90%–100% observed among clinical cases. The fitted model was consistent with prevailing consensus on pdmH1N1 transmission characteristics (e.g. initial reproductive number of 1.28 and mean generation time of 2.4 days which were within the consensus range), hence our ISP estimates were consistent with the transmission dynamics and temporal buildup of population-level immunity. IAR estimates in influenza seroprevalence studies are sensitive to seropositivity thresholds and ISP adjustments which in current practice are mostly chosen based on conventions instead of systematic criteria. Our results thus highlighted the need for reexamining conventional practice to develop standards for analyzing influenza serologic data (e.g. real-time assessment of bias in ISP adjustments by evaluating the consistency of IAR across multiple thresholds and with mixture models), especially in the context of pandemics when robustness and comparability of IAR estimates are most needed for informing situational awareness and risk assessment. The same principles are broadly applicable for seroprevalence studies of other infectious disease outbreaks.     

Isoform‐specific responses of metallothioneins in a marine pollution biomonitor,the green‐lipped mussel Perna viridis,towards different stress stimulations

Metallothioneins (MTs) are commonly used as biomarker for metal pollution assessment in marine ecosystems. Using integrated genomic and proteomic analyses, this study characterized two types of MT isoform in the digestive gland of a common biomonitor, the green‐lipped mussel Perna viridis, towards the challenges of a metal (cadmium; Cd) and a non‐metal oxidant (hydrogen peroxide; H₂O₂) respectively. The two isoforms differed in their deduced protein sequences, with 73 amino acids for MT10‐I and 72 for MT10‐II (a novel type), but both consisted of a high percentage (27.4 to 29.2%) of cysteine. Two‐dimensional gel and Western blot showed that the MT proteins were present in multiple isoform spots, and they were further validated to be MT10‐I and MT10‐II using MS analysis coupled with unrestricted modifications searching. Expression of mRNA revealed that MT10‐I responded promptly to Cd but had a lagged induction to H₂O₂ treatments, while MT10‐II was exclusively induced by Cd treatment over the course of exposure. Expression of the MT proteins also showed a delayed response to H₂O₂, compared to Cd treatments. This study uncovered the potential different functional roles of various MTs isoforms in P. viridis and thus advances the resolution of using MTs as biomarkers in future applications.     

Retracted: Upregulated microRNA-31 inhibits oxidative stress-induced neuronal injury through the JAK/STAT3 pathway by binding to PKD1 in mice with ischemic stroke

Ischemic stroke (IS), which is characterized by high morbidity, disability, and mortality, is recognized as a major cerebrovascular disease. MicroRNA-31 (miR-31) was reported to participate in the progression of brain disease. The present study was conducted in order to investigate the effect of miR-31 on oxidative stress-induced neuronal injury in IS mice with the involvement of protein kinase D1 (PKD1) and the JAK/STAT3 pathway. C57BL/6J mice were used to establish the middle cerebral artery occlusion (MCAO) model. Astrocytes were transfected with miR-31 mimic, miR-31 inhibitor, si-PKD1, or JAK-STAT3 pathway inhibitor. Following the establishment of an oxygen–glucose deprivation (OGD) model, the astrocytes were cocultured with neuronal OGD. Lower miR-31, higher PKD1 expressions, and activated JAK/STAT3 pathway were found in both the MCAO and OGD models. miR-31 could negatively target PKD1. In an MCAO model, overexpressing miR-31 and silencing PKD1 reduced neuronal injury, cerebral infarct volume, neuron loss, and oxidative stress injury, inhibited the activation of JAK/STAT3 pathway and the expressions of PKD1, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, malondialdehyde, 4-HNE, 8-HOdG, caspase-3, and Bax, but increased the superoxide dismutase content. In the OGD model, overexpression of miR-31 and silencing of PKD1 attenuated oxidative stress-induced neuronal injury, and diminished the lactate dehydrogenase leakage and reactive oxygen species level, accompanied by elevated neuronal viability. These results indicate that miR-31 alleviates inflammatory response as well as an oxidative stress-induced neuronal injury in IS mice by downregulating PKD1 and JAK/STAT3 pathway.