Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm.

The major hepatitis B virus (HBV) core protein is a viral structural protein involved in nucleic acid binding. Its coding sequence contains an extension of 29 codons (the "precore" region) at the amino terminus of the protein which is present in a fraction of the viral transcripts. This region is evolutionarily conserved among mammalian and avian HBVs, suggesting it has functional importance, although at least for duck HBV it has been shown to be nonessential for replication of infectious virions. Using in vitro assays for protein translocation across the endoplasmic reticulum membrane, we found that the precore region of the HBV genome encodes a signal sequence. This signal sequence was recognized by signal recognition particle, which targeted the nascent precore protein to the endoplasmic reticulum membrane with efficiencies comparable to those of other mammalian secretory proteins. A 19-amino acid signal peptide was removed by signal peptidase on the lumenal side of the microsomal membrane, generating a protein similar to the HBV major core protein, but containing 10 additional amino acids from the precore region at its amino terminus. Surprisingly, we found that 70-80% of this signal peptidase-cleaved product was localized on the cytoplasmic side of the microsomal vesicles and was not associated with the membranes. We conclude that translocation was aborted by an unknown mechanism, then the protein disengaged from the translocation machinery and was released back into the cytoplasm. Thus, a cytoplasmically disposed protein was created whose amino terminus resulted from signal peptidase cleavage. The remaining 20-30% appeared to be completely translocated into the lumen of the microsomes. A deletion mutant lacking the carboxy-terminal nucleic acid binding domain of the precore protein was similarly partitioned between the lumen of the microsomes and the cytoplasmic compartment, indicating that this highly charged domain is not responsible for the aborted translocation. We discuss the implications of our findings for the protein translocation process and suggest a possible role in the virus life cycle

Cross Saharan transport of water vapour via recycled cold-pool outflows from moist convection

Very sparse data has previously limited observational studies of meteorological processes in the Sahara. We present an observed case of convectively-driven water vapour transport crossing the Sahara over 2.5 days in June 2012, from the Sahel in the south to the Atlas in the north. A daily cycle is observed, with deep convection in the evening generating moist cold pools that fed the next day’s convection; the convection then generated new cold pools, providing a vertical recycling of moisture. Trajectories driven by analyses were able to capture the direction of the transport but not its full extent, particularly at night when cold pools are most active, and analyses missed much of the water content of cold pools. The results highlight the importance of cold pools for moisture transport, dust and clouds, and demonstrate the need to include these processes in models in order to improve the representation of Saharan atmospher

Observations of increased cloud cover over irrigated agriculture in an arid environment

Irrigated agriculture accounts for 20% of global cropland area and may alter climate locally and globally, but feedbacks on clouds and rainfall remain highly uncertain, particularly in arid regions. Non-renewable groundwater in arid regions accounts for 20% of global irrigation water demand, and quantifying these feedbacks is crucial for the prediction of long-term water use in a changing climate. Here we use satellite data to show how irrigated crops in an arid environment alter land-surface properties, cloud cover and rainfall patterns. Land surface temperatures (LST) over the cropland are 5-7 K lower than their surroundings, despite a lower albedo, suggesting that Bowen ratio is strongly reduced (and latent heat fluxes increased) over the irrigated cropland. Daytime cloud cover is increased by up to 15% points (a relative increase of 60%), with increased cloud development in the morning, and a greater afternoon peak in cloud. Cloud cover is significantly correlated with interannual variations in vegetation and LST. Afternoon rainfall also appears to be enhanced around the irrigation. The cloud feedback is the opposite of what has been previously observed in tropical and semiarid regions, suggesting different processes drive land-atmosphere feedbacks in very dry environments. Increased cloud and rainfall, and associated increases in diffuse radiation and reductions in temperature, are likely to benefit vegetation growth. Predictions of changes in crop productivity due to climate change and the impacts of global land-use change on climate and the use of water-resources would therefore benefit from including these effects

Structure formation in the presence of relativistic heat conduction: corrections to the Jeans wave number with a stable first order in the gradients formalism

The problem of structure formation in relativistic dissipative fluids was analyzed in a previous work within Eckart's framework, in which the heat flux is coupled to the hydrodynamic acceleration, additional to the usual temperature gradient term. It was shown that in such case, the pathological behavior of fluctuations leads to the disapperance of the gravitational instability responsible for structure formation. In the present work the problem is revisited now using a constitutive equation derived from relativistic kinetic theory. The new relation, in which the heat flux is not coupled to the hydrodynamic acceleration, leads to a consistent first order in the gradients formalism. In this case the gravitational instability remains, and only relativistic corrections to the Jeans wave number are obtained. In the calculation here shown the non-relativistc limit is recovered, opposite to what happens in Eckart's case.Comment: 10 pages, no figure

Age difference between heterosexual partners in Britain: Implications for the spread of Chlamydia trachomatis

Heterosexual partners often differ in age. Integrating realistic patterns of sexual mixing by age into dynamic transmission models has been challenging. The effects of these patterns on the transmission of sexually transmitted infections (STI) including Chlamydia trachomatis (chlamydia), the most common bacterial STI are not well understood. We describe age mixing between new heterosexual partners using age- and sex-specific data about sexual behavior reported by people aged 16-63 years in the 2000 and 2010 British National Surveys of Sexual Attitudes and Lifestyles. We incorporate mixing patterns into a compartmental transmission model fitted to age- and sex-specific, chlamydia positivity from the same surveys, to investigate C. trachomatis transmission. We show that distributions of ages of new sex partners reported by women and by men in Britain are not consistent with each other. After balancing these distributions, new heterosexual partnerships tend to involve men who are older than women (median age difference 2, IQR -1, 5 years). We identified the most likely age combinations of heterosexual partners where incident C. trachomatis infections are generated. The model results show that in >50% of chlamydia transmitting partnerships, at least one partner is ≥25 years old. This study illustrates how sexual behavior data can be used to reconstruct detailed sexual mixing patterns by age, and how these patterns can be integrated into dynamic transmission models. The proposed framework can be extended to study the effects of age-dependent transmission on incidence in any STI

Clouds over the summertime Sahara: an evaluation of Met Office retrievals from Meteosat Second Generation using airborne remote sensing

Novel methods of cloud detection are applied to airborne remote sensing observations from the unique Fennec aircraft dataset, to evaluate the Met Office-derived products on cloud properties over the Sahara based on the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) on-board the Meteosat Second Generation (MSG) satellite. Two cloud mask configurations are considered, as well as the retrievals of cloud-top height (CTH), and these products are compared to airborne cloud remote sensing products acquired during the Fennec campaign in June 2011 and June 2012. Most detected clouds (67 % of the total) have a horizontal extent that is smaller than a SEVIRI pixel (3 km  ×  3 km). We show that, when partially cloud-contaminated pixels are included, a match between the SEVIRI and aircraft datasets is found in 80 ± 8 % of the pixels. Moreover, under clear skies the datasets are shown to agree for more than 90 % of the pixels. The mean cloud field, derived from the satellite cloud mask acquired during the Fennec flights, shows that areas of high surface albedo and orography are preferred sites for Saharan cloud cover, consistent with published theories. Cloud-top height retrievals however show large discrepancies over the region, which are ascribed to limiting factors such as the cloud horizontal extent, the derived effective cloud amount, and the absorption by mineral dust. The results of the CTH analysis presented here may also have further-reaching implications for the techniques employed by other satellite applications facilities across the world

Knowledge is at the Edge! How to Search in Distributed Machine Learning Models

With the advent of the Internet of Things and Industry 4.0 an enormous amount of data is produced at the edge of the network. Due to a lack of computing power, this data is currently send to the cloud where centralized machine learning models are trained to derive higher level knowledge. With the recent development of specialized machine learning hardware for mobile devices, a new era of distributed learning is about to begin that raises a new research question: How can we search in distributed machine learning models? Machine learning at the edge of the network has many benefits, such as low-latency inference and increased privacy. Such distributed machine learning models can also learn personalized for a human user, a specific context, or application scenario. As training data stays on the devices, control over possibly sensitive data is preserved as it is not shared with a third party. This new form of distributed learning leads to the partitioning of knowledge between many devices which makes access difficult. In this paper we tackle the problem of finding specific knowledge by forwarding a search request (query) to a device that can answer it best. To that end, we use a entropy based quality metric that takes the context of a query and the learning quality of a device into account. We show that our forwarding strategy can achieve over 95% accuracy in a urban mobility scenario where we use data from 30 000 people commuting in the city of Trento, Italy.Comment: Published in CoopIS 201

The synergetic effect from the combination of different adsorption resins in batch and semi-continuous cultivations of S. Cerevisiae cell factories to produce acetylated Taxanes precursors of the anticancer drug Taxol

In situ product recovery is an efficient way to intensify bioprocesses as it can perform adsorption of the desired natural products in the cultivation. However, it is common to use only one adsorbent (liquid or solid) to perform the product recovery. For this study, the use of an in situ product recovery method with three combined commercial resins (HP-20, XAD7HP, and HP-2MG) with different chemical properties was performed. A new yeast strain of Saccharomyces cerevisiae was engineered using CRISPR Cas9 (strain EJ2) to deliver heterologous expression of oxygenated acetylated taxanes that are precursors of the anticancer drug Taxol ® (paclitaxel). Microscale cultivations using a definitive screening design (DSD) were set to get the best resin combinations and concentrations to retrieve high taxane titers. Once the best resin treatment was selected by the DSD, semi-continuous cultivation in high throughput microscale was performed to increase the total taxanes yield up to 783 ± 33 mg/L. The best T5α-yl Acetate yield obtained was up to 95 ± 4 mg/L, the highest titer of this compound ever reported by a heterologous expression. It was also observed that by using a combination of the resins in the cultivation, 8 additional uncharacterized taxanes were found in the gas chromatograms compared to the dodecane overlay method. Lastly, the cell-waste reactive oxygen species concentrations from the yeast were 1.5-fold lower in the resin's treatment compared to the control with no adsorbent aid. The possible future implications of this method could be critical for bioprocess intensification, allowing the transition to a semi-continuous flow bioprocess. Further, this new methodology broadens the use of different organisms for natural product synthesis/discovery benefiting from clear bioprocess intensification advantages

Delayed reperfusion deficits after experimental stroke account for increased pathophysiology.

Cerebral blood flow and oxygenation in the first few hours after reperfusion following ischemic stroke are critical for therapeutic interventions but are not well understood. We investigate changes in oxyhemoglobin (HbO(2)) concentration in the cortex during and after ischemic stroke, using multispectral optical imaging in anesthetized mice, a remote filament to induce either 30 minute middle cerebral artery occlusion (MCAo), sham surgery or anesthesia alone. Immunohistochemistry establishes cortical injury and correlates the severity of damage with the change of oxygen perfusion. All groups were imaged for 6 hours after MCAo or sham surgery. Oxygenation maps were calculated using a pathlength scaling algorithm. The MCAo group shows a significant drop in HbO(2) during occlusion and an initial increase after reperfusion. Over the subsequent 6 hours HbO(2) concentrations decline to levels below those observed during stroke. Platelets, activated microglia, interleukin-1α, evidence of BBB breakdown and neuronal stress increase within the stroked hemisphere and correlate with the severity of the delayed reperfusion deficit but not with the ΔHbO(2) during stroke. Despite initial restoration of HbO(2) after 30 min MCAo there is a delayed compromise that coincides with inflammation and could be a target for improved stroke outcome after thrombolysis