Halcyornis toliapicus (aves: Lower Eocene, England) indicates advanced neuromorphology in Mesozoic Neornithes

Our recent X-ray micro computer-tomographic (μCT) investigations of Prophaethon shrubsolei and Odontopteryx toliapica from the Lower Eocene London Clay Formation of England revealed the avian brain to have been essentially modern in form by 55 Ma, but that an important vision-related synapomorphy of living birds, the eminentia sagittalis of the telencephalon, was poorly developed. This evidence suggested that the feature probably appeared close to the end of the Mesozoic. Here we use μCT analysis to describe the endocranium of Halcyornis toliapicus, also from the London Clay Formation. The affinities of Halcyornis have been hotly debated, with the taxon referred to the Charadriiformes (Laridae), Coraciiformes (Alcedinidae, and its own family Halcyornithidae) and most recently that Halcyornithidae may be a possible senior synonym of Pseudasturidae (Pan-Psittaciformes). Unlike Prophaethon and Odontopteryx, the eminentia sagittalis of Halcyornis is strongly developed and comparable to that of living species. Like those London Clay taxa, the eminentia sagittalis occupies a rostral position on the telencephalon. The senses of Halcyornis appear to have been well developed. The length of the cochlear duct of the inner ear indicates a hearing sensitivity within the upper range of living species, and enlarged olfactory lobes suggest a reasonable reliance on sense of smell. The optic nerves were especially well developed which, together with the strong development of the eminentia sagittalis, indicates a high degree of visual specialization in Halcyornis. The advanced development of the eminentia sagittalis further supports a Mesozoic age for the appearance of this structure and associated neural architectural complexity found in extant Aves. The eminentia sagittalis of living Psittaciformes is situated caudally on the telencephalon, making a Pan-Psittaciformes relationship unlikely for Halcyorni

Western Indian Ocean marine and terrestrial records of climate variability: a review and new concepts on land-ocean interactions since AD 1660

We examine the relationship between three tropical and two subtropical western Indian Ocean coral oxygen isotope time series to surface air temperatures (SAT) and rainfall over India, tropical East Africa and southeast Africa. We review established relationships, provide new concepts with regard to distinct rainfall seasons, and mean annual temperatures. Tropical corals are coherent with SAT over western India and East Africa at interannual and multidecadal periodicities. The subtropical corals correlate with Southeast African SAT at periodicities of 16–30 years. The relationship between the coral records and land rainfall is more complex. Running correlations suggest varying strength of interannual teleconnections between the tropical coral oxygen isotope records and rainfall over equatorial East Africa. The relationship with rainfall over India changed in the 1970s. The subtropical oxygen isotope records are coherent with South African rainfall at interdecadal periodicities. Paleoclimatological reconstructions of land rainfall and SAT reveal that the inferred relationships generally hold during the last 350 years. Thus, the Indian Ocean corals prove invaluable for investigating land–ocean interactions during past centuries

An Ancient Relation between Units of Length and Volume Based on a Sphere

The modern metric system defines units of volume based on the cube. We propose that the ancient Egyptian system of measuring capacity employed a similar concept, but used the sphere instead. When considered in ancient Egyptian units, the volume of a sphere, whose circumference is one royal cubit, equals half a hekat. Using the measurements of large sets of ancient containers as a database, the article demonstrates that this formula was characteristic of Egyptian and Egyptian-related pottery vessels but not of the ceramics of Mesopotamia, which had a different system of measuring length and volume units

Building Irish families through surrogacy: medical and judicial issues for the advanced reproductive technologies

Surrogacy involves one woman (surrogate mother) carrying a child for another person/s (commissioning person/couple), based on a mutual agreement requiring the child to be handed over to the commissioning person/couple following birth. Reasons for seeking surrogacy include situations where a woman has non-functional or absent reproductive organs, or as a remedy for recurrent pregnancy loss. Additionally, surrogacy may find application in any medical context where pregnancy is contraindicated, or where a couple consisting of two males seek to become parents through oocyte donation. Gestational surrogacy is one of the main issues at the forefront of bioethics and the advanced reproductive technologies, representing an important challenge to medical law. This analysis reviews the history of surrogacy and clinical and legal issues pertaining to this branch of reproductive medicine. Interestingly, the Medical Council of Ireland does not acknowledge surrogacy in its current practice guidelines, nor is there specific legislation addressing surrogacy in Ireland at present. We therefore have developed a contract-based model for surrogacy in which, courts in Ireland may consider when confronted with a surrogacy dispute, and formulated a system to resolve any potential dispute arising from a surrogacy arrangement. While the 2005 report by the Commission on Assisted Human Reproduction (CAHR) is an expert opinion guiding the Oireachtas' development of specific legislation governing assisted human reproduction and surrogacy, our report represents independent scholarship on the contractual elements of surrogacy with particular focus on how Irish courts might decide on surrogacy matters in a modern day Ireland. This joint medico-legal collaborative also reviews the contract for services arrangement between the commissioning person/s and the surrogate, and the extent to which the contract may be enforced

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis : First-in-human trial of ChAd63-KH

BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359)

B Cell: T Cell Interactions Occur within Hepatic Granulomas during Experimental Visceral Leishmaniasis

Hepatic resistance to Leishmania donovani infection in mice is associated with the development of granulomas, in which a variety of lymphoid and non-lymphoid populations accumulate. Although previous studies have identified B cells in hepatic granulomas and functional studies in B cell-deficient mice have suggested a role for B cells in the control of experimental visceral leishmaniasis, little is known about the behaviour of B cells in the granuloma microenvironment. Here, we first compared the hepatic B cell population in infected mice, where ≈60% of B cells are located within granulomas, with that of naïve mice. In infected mice, there was a small increase in mIgMlomIgD+ mature B2 cells, but no enrichment of B cells with regulatory phenotype or function compared to the naïve hepatic B cell population, as assessed by CD1d and CD5 expression and by IL-10 production. Using 2-photon microscopy to quantify the entire intra-granuloma B cell population, in conjunction with the adoptive transfer of polyclonal and HEL-specific BCR-transgenic B cells isolated from L. donovani-infected mice, we demonstrated that B cells accumulate in granulomas over time in an antigen-independent manner. Intra-vital dynamic imaging was used to demonstrate that within the polyclonal B cell population obtained from L. donovani-infected mice, the frequency of B cells that made multiple long contacts with endogenous T cells was greater than that observed using HEL-specific B cells obtained from the same inflammatory environment. These data indicate, therefore, that a subset of this polyclonal B cell population is capable of making cognate interactions with T cells within this unique environment, and provide the first insights into the dynamics of B cells within an inflammatory site

Deficiency of Leishmania phosphoglycans influences the magnitude but does not affect the quality of secondary (memory) anti-Leishmania immunity

Despite inducing very low IFN-γ response and highly attenuated in vivo, infection of mice with phosphoglycan (PG) deficient Leishmania major (lpg2-) induces protection against virulent L. major challenge. Here, we show that mice infected with lpg2- L. major generate Leishmania-specific memory T cells. However, in vitro and in vivo proliferation, IL-10 and IFN-γ production by lpg2- induced memory cells were impaired in comparison to those induced by wild type (WT) parasites. Interestingly, TNF recall response was comparable to WT infected mice. Despite the impaired proliferation and IFN-γ response, lpg2- infected mice were protected against virulent L. major challenge and their T cells mediated efficient infection-induced immunity. In vivo depletion and neutralization studies with mAbs demonstrated that lpg2- L. major-induced resistance was strongly dependent on IFN-γ, but independent of TNF and CD8(+) T cells. Collectively, these data show that the effectiveness of secondary anti-Leishmania immunity depends on the quality (and not the magnitude) of IFN-γ response. These observations provide further support for consideration of lpg2- L. major as a live-attenuated candidate for leishmanization in humans since it protects strongly against virulent challenge, without inducing pathology in infected animals

Rapid interhemispheric climate links via the Australasian monsoon during the last deglaciation

Recent studies have proposed that millennial-scale reorganization of the ocean-atmosphere circulation drives increased upwelling in the Southern Ocean, leading to rising atmospheric carbon dioxide levels and ice age terminations. Southward migration of the global monsoon is thought to link the hemispheres during deglaciation, but vital evidence from the southern sector of the vast Australasian monsoon system is yet to emerge. Here we present a 230thorium-dated stalagmite oxygen isotope record of millennial-scale changes in Australian–Indonesian monsoon rainfall over the last 31,000 years. The record shows that abrupt southward shifts of the Australian–Indonesian monsoon were synchronous with North Atlantic cold intervals 17,600–11,500 years ago. The most prominent southward shift occurred in lock-step with Heinrich Stadial 1 (17,600–14,600 years ago), and rising atmospheric carbon dioxide. Our findings show that millennial-scale climate change was transmitted rapidly across Australasia and lend support to the idea that the 3,000-year-long Heinrich 1 interval could have been critical in driving the last deglaciation

The role of historical and contemporary processes on phylogeographic structure and genetic diversity in the Northern Cardinal, Cardinalis cardinalis

Background Earth history events such as climate change are believed to have played a major role in shaping patterns of genetic structure and diversity in species. However, there is a lag between the time of historical events and the collection of present-day samples that are used to infer contemporary population structure. During this lag phase contemporary processes such as dispersal or non-random mating can erase or reinforce population differences generated by historical events. In this study we evaluate the role of both historical and contemporary processes on the phylogeography of a widespread North American songbird, the Northern Cardinal, Cardinalis cardinalis. Results Phylogenetic analysis revealed deep mtDNA structure with six lineages across the species\u27 range. Ecological niche models supported the same geographic breaks revealed by the mtDNA. A paleoecological niche model for the Last Glacial Maximum indicated that cardinals underwent a dramatic range reduction in eastern North America, whereas their ranges were more stable in México. In eastern North America cardinals expanded out of glacial refugia, but we found no signature of decreased genetic diversity in areas colonized after the Last Glacial Maximum. Present-day demographic data suggested that population growth across the expansion cline is positively correlated with latitude. We propose that there was no loss of genetic diversity in areas colonized after the Last Glacial Maximum because recent high-levels of gene flow across the region have homogenized genetic diversity in eastern North America. Conclusion We show that both deep historical events as well as demographic processes that occurred following these events are critical in shaping genetic pattern and diversity in C. cardinalis. The general implication of our results is that patterns of genetic diversity are best understood when information on species history, ecology, and demography are considered simultaneously