Molecular Phylogeny and Historical Biogeography of the Neotropical Swarm-Founding Social Wasp Genus Synoeca (Hymenoptera: Vespidae)

The Neotropical Region harbors high biodiversity and many studies on mammals, reptiles, amphibians and avifauna have investigated the causes for this pattern. However, there is a paucity of such studies that focus on Neotropical insect groups. Synoeca de Saussure, 1852 is a Neotropical swarm-founding social wasp genus with five described species that is broadly and conspicuously distributed throughout the Neotropics. Here, we infer the phylogenetic relationships, diversification times, and historical biogeography of Synoeca species. We also investigate samples of the disjoint populations of S. septentrionalis that occur in both northwestern parts of South America through Central American and the Brazilian Atlantic rainforests. Our results showed that the interspecific relationships for Synoeca could be described as follows: (S. chalibea + S. virginea) + (S. cyanea + (S. septentrionalis/S. surinama)). Notably, samples of S. septentrionalis and S. surinama collected in the Atlantic Forest were interrelated and may be the result of incomplete lineage sorting and/or mitochondrial introgression among them. Our Bayesian divergence dating analysis revealed recent Plio-Pleistocene diversification in Synoeca. Moreover, our biogeographical analysis suggested an Amazonian origin of Synoeca, with three main dispersal events subsequently occurring during the Plio-Pleistocene.     

Effective Treatment of Established GL261 Murine Gliomas through Picornavirus Vaccination-Enhanced Tumor Antigen-Specific CD8+ T Cell Responses

Glioblastoma (GBM) is among the most invasive and lethal of cancers, frequently infiltrating surrounding healthy tissue and giving rise to rapid recurrence. It is therefore critical to establish experimental model systems and develop therapeutic approaches that enhance anti-tumor immunity. In the current study, we have employed a newly developed murine glioma model to assess the efficacy of a novel picornavirus vaccination approach for the treatment of established tumors. The GL261-Quad system is a variation of the GL261 syngeneic glioma that has been engineered to expresses model T cell epitopes including OVA_257–264. MRI revealed that both GL261 and GL261-Quad tumors display characteristic features of human gliomas such as heterogeneous gadolinium leakage and larger T2 weighted volumes. Analysis of brain-infiltrating immune cells demonstrated that GL261-Quad gliomas generate detectable CD8+ T cell responses toward the tumor-specific K^b:OVA_257–264 antigen. Enhancing this response via a single intracranial or peripheral vaccination with picornavirus expressing the OVA_257–264 antigen increased anti-tumor CD8+ T cells infiltrating the brain, attenuated progression of established tumors, and extended survival of treated mice. Importantly, the efficacy of the picornavirus vaccination is dependent on functional cytotoxic activity of CD8+ T cells, as the beneficial response was completely abrogated in mice lacking perforin expression. Therefore, we have developed a novel system for evaluating mechanisms of anti-tumor immunity in vivo, incorporating the GL261-Quad model, 3D volumetric MRI, and picornavirus vaccination to enhance tumor-specific cytotoxic CD8+ T cell responses and track their effectiveness at eradicating established gliomas in vivo.     

Mycorrhiza Symbiosis Increases the Surface for Sunlight Capture in Medicago truncatula for Better Photosynthetic Production

Arbuscular mycorrhizal (AM) fungi play a prominent role in plant nutrition by supplying mineral nutrients, particularly inorganic phosphate (P_i), and also constitute an important carbon sink. AM stimulates plant growth and development, but the underlying mechanisms are not well understood. In this study, Medicago truncatula plants were grown with Rhizophagus irregularis BEG141 inoculum (AM), mock inoculum (control) or with P_i fertilization. We hypothesized that AM stimulates plant growth through either modifications of leaf anatomy or photosynthetic activity per leaf area. We investigated whether these effects are shared with P_i fertilization, and also assessed the relationship between levels of AM colonization and these effects. We found that increased P_i supply by either mycorrhization or fertilization led to improved shoot growth associated with increased nitrogen uptake and carbon assimilation. Both mycorrhized and P_i-fertilized plants had more and longer branches with larger and thicker leaves than the control plants, resulting in an increased photosynthetically active area. AM-specific effects were earlier appearance of the first growth axes and increased number of chloroplasts per cell section, since they were not induced by P_i fertilization. Photosynthetic activity per leaf area remained the same regardless of type of treatment. In conclusion, the increase in growth of mycorrhized and P_i-fertilized Medicago truncatula plants is linked to an increase in the surface for sunlight capture, hence increasing their photosynthetic production, rather than to an increase in the photosynthetic activity per leaf area.     

Developmental Changes in ERP Responses to Spatial Frequencies

Social interaction starts with perception of other persons. One of the first steps in perception is processing of basic information such as spatial frequencies (SF), which represent details and global information. However, although behavioural perception of SF is well investigated, the developmental trajectory of the temporal characteristics of SF processing is not yet well understood. The speed of processing of this basic visual information is crucial, as it determines the speed and possibly accuracy of subsequent visual and social processes. The current study investigated developmental changes in the temporal characteristics of selective processing of high SF (HSF; details) versus low SF (LSF; global). To this end, brain activity was measured using EEG in 108 children aged 3–15 years, while HSF or LSF grating stimuli were presented. Interest was in the temporal characteristics of brain activity related to LSF and HSF processing, specifically at early (N80) or later (P1 or N2) peaks in brain activity. Analyses revealed that from 7–8 years onwards HSF but not LSF stimuli evoked an N80 peak. In younger children, aged 3–8 years, the visual manipulation mainly affected the visual N2 peak. Selective processing of HSF versus LSF thus occurs at a rather late time-point (N2 peak) in young children. Although behavioural research previously showed that 3–6 year-olds can perceive detailed information, the current results point out that selective processing of HSF versus LSF is still delayed in these children. The delayed processing in younger children could impede the use of LSF and HSF for emotional face processing. Thus, the current study is a starting point for understanding changes in basic visual processing which underlie social development.     

Trend of Narratives in the Age of Misinformation

Social media enabled a direct path from producer to consumer of contents changing the way users get informed, debate, and shape their worldviews. Such a disintermediation might weaken consensus on social relevant issues in favor of rumors, mistrust, or conspiracy thinking—e.g., chem-trails inducing global warming, the link between vaccines and autism, or the New World Order conspiracy. Previous studies pointed out that consumers of conspiracy-like content are likely to aggregate in homophile clusters—i.e., echo-chambers. Along this path we study, by means of a thorough quantitative analysis, how different topics are consumed inside the conspiracy echo-chamber in the Italian Facebook. Through a semi-automatic topic extraction strategy, we show that the most consumed contents semantically refer to four specific categories: environment, diet, health, and geopolitics. We find similar consumption patterns by comparing users activity (likes and comments) on posts belonging to these different semantic categories. Finally, we model users mobility across the distinct topics finding that the more a user is active, the more he is likely to span on all categories. Once inside a conspiracy narrative users tend to embrace the overall corpus.     

Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

Background/Aim

New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.

Methods

To estimate the HCV antibody and HCV-RNA (chronic infection) prevalence among the metropolitan Chicago PWID population, we used empirical data from three large epidemiological studies. Cost of DAAs is assumed $50,000 per person.

Results

Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID (69% of the total PWID population) attend harm reduction (HR) programs, such as syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There are about 11,000 young PWID (<30 years old) with an estimated HCV-RNA prevalence of 10% (PWID in these two subpopulations overlap). The model suggests that the following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence by one-half over 10 years of treatment [cost per year, min-max in millions]: 35 per 1,000 [$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID.

Conclusions

Treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago, who are the main reservoir for on-going HCV transmission. Focusing treatment on PWID attending HR programs and/or young PWID could have a significant impact on HCV prevalence in these subpopulations at an attainable cost.     

Genetic and Informatic Analyses Implicate Kif12 as a Candidate Gene within the Mpkd2 Locus That Modulates Renal Cystic Disease Severity in the Cys1cpk Mouse

We have previously mapped the interval on Chromosome 4 for a major polycystic kidney disease modifier (Mpkd) of the B6(Cg)-Cys1 ^cpk/J mouse model of recessive polycystic kidney disease (PKD). Informatic analyses predicted that this interval contains at least three individual renal cystic disease severity-modulating loci (Mpkd1-3). In the current study, we provide further validation of these predicted effects using a congenic mouse line carrying the entire CAST/EiJ (CAST)-derived Mpkd1-3 interval on the C57BL/6J background. We have also generated a derivative congenic line with a refined CAST-derived Mpkd1-2 interval and demonstrated its dominantly-acting disease-modulating effects (e.g., 4.2-fold increase in total cyst area; p<0.001). The relative strength of these effects allowed the use of recombinants from these crosses to fine map the Mpkd2 effects to a <14 Mbp interval that contains 92 RefSeq sequences. One of them corresponds to the previously described positional Mpkd2 candidate gene, Kif12. Among the positional Mpkd2 candidates, only expression of Kif12 correlates strongly with the expression pattern of Cys1 across multiple anatomical nephron structures and developmental time points. Also, we demonstrate that Kif12 encodes a primary cilium-associated protein. Together, these data provide genetic and informatic validation of the predicted renal cystic disease-modulating effects of Mpkd1-3 loci and implicate Kif12 as the candidate locus for Mpkd2.     

Characterisation of the Small RNAs in the Biomedically Important Green-Bottle Blowfly Lucilia sericata

Background

The green bottle fly maggot, Lucilia sericata, is a species with importance in medicine, agriculture and forensics. Improved understanding of this species’ biology is of great potential benefit to many research communities. MicroRNAs (miRNA) are a short non-protein coding regulatory RNA, which directly regulate a host of protein coding genes at the translational level. They have been shown to have developmental and tissue specific distributions where they impact directly on gene regulation. In order to improve understanding of the biology of L. sericata maggots we have performed small RNA-sequencing of their secretions and tissue at different developmental stages.

Results

We have successfully isolated RNA from the secretions of L. sericata maggots. Illumina small RNA-sequencing of these secretions and the three tissues (crop, salivary gland, gut) revealed that the most common small RNA fragments were derived from ribosomal RNA and transfer RNAs of both insect and bacterial origins. These RNA fragments were highly specific, with the most common tRNAs, such as GlyGCC, predominantly represented by reads derived from the 5’ end of the mature maggot tRNA. Each library also had a unique profile of miRNAs with a high abundance of miR-10-5p in the maggot secretions and gut and miR-8 in the food storage organ the crop and salivary glands. The pattern of small RNAs in the bioactive maggot secretions suggests they originate from a combination of saliva, foregut and hindgut tissues. Droplet digital RT-PCR validation of the RNA-sequencing data shows that not only are there differences in the tissue profiles for miRNAs and small RNA fragments but that these are also modulated through developmental stages of the insect.

Conclusions

We have identified the small-RNAome of the medicinal maggots L. sericata and shown that there are distinct subsets of miRNAs expressed in specific tissues that also alter during the development of the insect. Furthermore there are very specific RNA fragments derived from other non-coding RNAs present in tissues and in the secretions. This new knowledge has applicability in diverse research fields including wound healing, agriculture and forensics.