Genetic diversity, biogeography and the morpho-genetic relationship in extant planktonic forminifera

Planktonic foraminifera are widely used as proxies for the reconstruction of past ocean conditions, a method that requires exact species classification and knowledge of their ecological adaptations. Species classification traditionally was conducted using morphological characteristics of the calcite shell. The application of genetic approaches on living planktonic foraminifera, however, challenged the classical species concept, by discovering a large number of cryptic species within the morphospecies. The present dissertation aims at establishing a connection between the fossil record and the genetic background of extant species by finding out to what degree morphologically defined species reflect real biological diversity. Molecular genetic techniques in combination with morphometric analyses were used to examine the extent of cryptic diversity in selected morphospecies and its relation to morphological traits. Furthermore, the biogeographic distribution patterns of extant species were analyzed in order to differentiate between species with local adaptations and endemism versus species with global dispersal and gene flow

Sedimentary ancient DNA: a new paleogenomic tool for reconstructing the history of marine ecosystems

Sedimentary ancient DNA (sedaDNA) offers a novel retrospective approach to reconstructing the history of marine ecosystems over geological timescales. Until now, the biological proxies used to reconstruct paleoceanographic and paleoecological conditions were limited to organisms whose remains are preserved in the fossil record. The development of ancient DNA analysis techniques substantially expands the range of studied taxa, providing a holistic overview of past biodiversity. Future development of marine sedaDNA research is expected to dramatically improve our understanding of how the marine biota responded to changing environmental conditions. However, as an emerging approach, marine sedaDNA holds many challenges, and its ability to recover reliable past biodiversity information needs to be carefully assessed. This review aims to highlight current advances in marine sedaDNA research and to discuss potential methodological pitfalls and limitations

Phylogeography of the tropical planktonic foraminifera lineage Globigerinella reveals isolation inconsistent with passive dispersal by ocean currents

Morphologically defined species of marine plankton often harbor a considerable level of cryptic diversity. Since many morphospecies show cosmopolitan distribution, an understanding of biogeographic and evolutionary processes at the level of genetic diversity requires global sampling. We use a database of 387 single-specimen sequences of the SSU rDNA of the planktonic foraminifera Globigerinella as a model to assess the biogeographic and phylogenetic distributions of cryptic diversity in marine microplankton on a global scale. Our data confirm the existence of multiple, well isolated genetic lineages. An analysis of their abundance and distribution indicates that our sampling is likely to approximate the actual total diversity. Unexpectedly, we observe an uneven allocation of cryptic diversity among the phylogenetic lineages. We show that this pattern is neither an artifact of sampling intensity nor a function of lineage age. Instead, we argue that it reflects an ongoing speciation process in one of the three major lineages. Surprisingly, four of the six genetic types in the hyperdiverse lineage are biogeographically restricted to the Indopacific. Their mutual co-occurrence and their hierarchical phylogenetic structure provide no evidence for an origin through sudden habitat fragmentation and their limitation to the Indopacific challenges the view of a global gene flow within the warm-water provinces. This phenomenon shows that passive dispersal is not sufficient to describe the distribution of plankton diversity. Rather, these organisms show differentiated distribution patterns shaped by species interactions and reflecting phylogenetic contingency with unique histories of diversification rates

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Modelled gamete fusion numbers in planktonic foraminifera

Reproductive biology is integral to evolutionary processes in organisms, yet gaining detailed insights poses major challenges. Planktonic Foraminifera are globally distributed marine protists and important contributors to the global carbon cycle with distinct biodiversity patterns. Knowledge on their life cycle remains incomplete, yet the production of flagellated gametes implies a sexual mode of reproduction. In the open ocean, this would rely on sufficient gamete encounters to maintain viable populations, which is problematic for protist plankton with low population densities. We applied dynamic modelling with parameters based on prior observations to verify if random gamete encounters are sufficient for maintaining viable populations. Temporal and spatial synchronization of gamete release seems inevitable to that end, and planktonic Foraminifera seemingly optimized their individual reproductive success at the expense of gene flow. This may explain their high degree of diversity and contributes to our understanding of plankton ecology and evolution

Seasonal and interannual variability in population dynamics of planktic foraminifers off Puerto Rico (Caribbean Sea)

The state of a population of planktic foraminifers at a certain time reflects multiple processes in the upper ocean, including environmental conditions to which the population was exposed during its growth, the age of the cohorts, and spatiotemporal patchiness. We carried out depth-stratified (0–60, 60–100 m) replicated sampling off Puerto Rico in autumn 2012, revisiting three stations previously sampled in autumn 1994 and spring 1995, in order to analyze seasonal and interannual variability of planktic foraminifers and the stable isotopic composition of their tests. The merged dataset from all three sampling campaigns allows us to assess short- and long-term changes in foraminiferal population dynamics and the spatial assemblage coherency along the shelf edge. All three sample series cover more than 2 weeks during either spring (1995) or autumn (1994, 2012) and include the time of the full moon when reproduction of some surface-dwelling planktic foraminifers has been postulated to take place. Our analyses indicate that interannual variability affected the faunal composition, and both autumn assemblages were characterized by oligotrophic tropical species, dominated by Trilobatus sacculifer and Globigerinoides ruber (white and pink variety). However, G. ruber (white) had a higher abundance in 1994 (37 %) than in 2012 (3.5 %), which may be partially due to increasing sea surface temperatures since the 1990s. Between 60 and 100 m water depth, a different faunal composition with a specific stable oxygen isotope signature provides evidence for the presence of the Subtropical Underwater at the sampling site. Measurements on T. sacculifer sampled in autumn 2012 revealed that test size, calcification and incidence of sac-like chambers continued to increase after full moon, and thus no relation to the synodic lunar reproduction cycle was recognized. During autumn 2012, outer bands of hurricane Sandy passed the Greater Antilles and likely affected the foraminifers. Lower standing stocks of living planktic foraminifers and lower stable carbon isotope values from individuals collected in the mixed layer likely indicate the response to increased rainfall and turbidity in the wake of the hurricane