Active immunization combined with cisplatin confers enhanced therapeutic protection and prevents relapses of HPV-induced tumors at different anatomical sites

The active immunotherapy concept relies on the use of vaccines that are capable of inducing antitumor immunity, reversion of the suppressive immunological environment, and long-term memory responses. Previously, antitumor vaccines based on a recombinant plasmid (pgDE7h) or a purified protein (gDE7) led to regression of early-established human papillomavirus (HPV)-associated tumors in a preclinical model. In this work, the anticancer vaccines were combined with cisplatin to treat HPV-induced tumors at advanced growth stages. The antitumor effects were evaluated in terms of tumor regression, induction of specific CD8⁺ T cells, and immune modulation of the tumor microenvironment. Acute toxicity induced by the treatment was measured by weight loss and histological alterations in the liver and kidneys. Our results revealed that the combination of cisplatin with either one of the tested immunotherapies (pgDE7h or gDE7) led to complete tumor regression in mice. Also, the combined treatment resulted in synergistic effects, particularly among mice immunized with gDE7, including activation of systemic and tumor-infiltrating E7-specific CD8⁺ T cells, tumor infiltration of macrophages and dendritic cells, and prevention of tumor relapses at different anatomical sites. Furthermore, the protocol allowed the reduction of cisplatin dosage and its intrinsic toxic effects, without reducing antitumor outcomes. These results expand our knowledge of active immunotherapy protocols and open perspectives for alternative treatments of HPV-associated tumors.     

First records of dive durations for a hibernating sea turtle

The first published record, from the early 1970s, of hibernation in sea turtles is based on the reports of the indigenous Indians and fishermen from Mexico, who hunted dormant green turtles (Chelonia mydas) in the Gulf of California. However, there were no successful attempts to investigate the biology of this particular behaviour further. Hence, data such as the exact duration and energetic requirements of dormant winter submergences are lacking. We used new satellite relay data loggers to obtain the first records of up to 7h long dives of a loggerhead turtle (Caretta caretta) overwintering in Greek waters. These represent the longest dives ever reported for a diving marine vertebrate. There is strong evidence that the dives were aerobic, because the turtle surfaced only for short intervals and before the calculated oxygen stores were depleted. This evidence suggests that the common belief that sea turtles hibernate underwater, as some freshwater turtles do, is incorrect.     

trEST, trGEN and Hits: access to databases of predicted protein sequences

High throughput genome (HTG) and expressed sequence tag (EST) sequences are currently the most abundant nucleotide sequence classes in the public database. The large volume, high degree of fragmentation and lack of gene structure annotations prevent efficient and effective searches of HTG and EST data for protein sequence homologies by standard search methods. Here, we briefly describe three newly developed resources that should make discovery of interesting genes in these sequence classes easier in the future, especially to biologists not having access to a powerful local bioinformatics environment. trEST and trGEN are regularly regenerated databases of hypothetical protein sequences predicted from EST and HTG sequences, respectively. Hits is a web-based data retrieval and analysis system providing access to precomputed matches between protein sequences (including sequences from trEST and trGEN) and patterns and profiles from Prosite and Pfam. The three resources can be accessed via the Hits home page (http://hits. isb-sib.ch).     

Genome of alkaliphilic Bacillus pseudofirmus OF4 reveals adaptations that support the ability to grow in an external pH range from 7.5 to 11.4

Bacillus pseudofirmus OF4 is an extreme but facultative alkaliphile that grows non-fermentatively in a pH range from 7.5 to above 11.4 and can withstand large sudden increases in external pH. It is a model organism for studies of bioenergetics at high pH, at which energy demands are higher than at neutral pH because both cytoplasmic pH homeostasis and ATP synthesis require more energy. The alkaliphile also tolerates a cytoplasmic pH?>?9.0 at external pH values at which the pH homeostasis capacity is exceeded, and manages other stresses that are exacerbated at alkaline pH, e.g. sodium, oxidative and cell wall stresses. The genome of B.?pseudofirmus OF4 includes two plasmids that are lost from some mutants without viability loss. The plasmids may provide a reservoir of mobile elements that promote adaptive chromosomal rearrangements under particular environmental conditions. The genome also reveals a more acidic pI profile for proteins exposed on the outer surface than found in neutralophiles. A large array of transporters and regulatory genes are predicted to protect the alkaliphile from its overlapping stresses. In addition, unanticipated metabolic versatility was observed, which could ensure requisite energy for alkaliphily under diverse conditions.     

Nasopharyngeal Tonsils (Adenoids) Contain Extrathymic Corticothymocytes

Adenoidal tissue (also known as nasopharyngeal tonsils) of 58% of humans in the pediatric age group contains immature T-lymphoid cells with the phenotype of thymocytes (TdT+,CD1abc+, cytoplasmic CD3+, coexpressing CD4 and CD8, lacking an Intraepithelial Lymphocyte-associated phenotype). The notable difference in comparison to palatine tonsils is the clustering in groups and sheets, comprising hundreds or thousands of cells (1.7%±0.2 of total T cells). The thymic epithelium is morphologically and phenotypically absent. Adenoids share with tonsils and lymph nodes the presence of immature B cell precursors (TdT+, CD1a-, Pax5+, Surrogate light chain±), however in these latter the presence of TdT+, CD1a+, Pax5- precursors is absent or limited to individual cells. Human adenoids are distinct among the Waldeyer''s ring lymphoid tissue because of the known embryogenic derivation from the third pharyngeal pouch, from which the thymus develops; in addition, they may display phenotypic incomplete features of a vestigial thymus.     

Predicting spatial patterns of soil bacteria under current and future environmental conditions

Soil bacteria are largely missing from future biodiversity assessments hindering comprehensive forecasts of ecosystem changes. Soil bacterial communities are expected to be more strongly driven by pH and less by other edaphic and climatic factors. Thus, alkalinisation or acidification along with climate change may influence soil bacteria, with subsequent influences for example on nutrient cycling and vegetation. Future forecasts of soil bacteria are therefore needed. We applied species distribution modelling (SDM) to quantify the roles of environmental factors in governing spatial abundance distribution of soil bacterial OTUs and to predict how future changes in these factors may change bacterial communities in a temperate mountain area. Models indicated that factors related to soil (especially pH), climate and/or topography explain and predict part of the abundance distribution of most OTUs. This supports the expectations that microorganisms have specific environmental requirements (i.e., niches/envelopes) and that they should accordingly respond to environmental changes. Our predictions indicate a stronger role of pH over other predictors (e.g. climate) in governing distributions of bacteria, yet the predicted future changes in bacteria communities are smaller than their current variation across space. The extent of bacterial community change predictions varies as a function of elevation, but in general, deviations from neutral soil pH are expected to decrease abundances and diversity of bacteria. Our findings highlight the need to account for edaphic changes, along with climate changes, in future forecasts of soil bacteria.Subject terms: Microbial ecology, Metagenomics, Climate-change ecology