Facile Synthesis of a Stable Side-on Phosphinyne Complex by Redox Driven Intramolecular Cyclisation

Alkyne complexes with vicinal substitution by a Lewis acid and a Lewis base at the coordinated alkyne are prospective frustrated Lewis pairs exhibiting a particular mutual distance and, hence, a specific activation potential. In this contribution, investigations on the generation of a WII alkyne complex bearing a phosphine as Lewis base and a carbenium group as Lewis acid are presented. Independently on potential substrates added, an intramolecular cyclisation product was always isolated. A subsequent deprotonation step led to an unprecedented side-on λ5-phosphinyne complex, which is interpreted as highly zwitterionic according to visible absorption spectroscopy supported by TD-DFT. Low-temperature 31P NMR and EPR spectroscopic measurements combined with time-dependent IR-spectroscopic monitoring provided insights in the mechanism of the cyclisation reaction. Decomposition of the multicomponent IR spectra by multivariate curve resolution and a kinetic hard-modelling approach allowed the derivation of kinetic parameters. Assignment of the individual IR spectra to potential intermediates was provided by DFT calculations. © 2020 The Authors. Published by Wiley-VCH Gmb

Magnitude of Alloresponses to MHC Class I/II Expressing Human Cardiac Myocytes is Limited by their Intrinsic Ability to Process and Present Antigenic Peptides

In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1) to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR β1*0301) pulsed with the influenza A matrix 1 (58-66) peptide (M1) were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC). Pretreatment of these M1-VAC targets with IFN-γ partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-γ pretreated W-1's could not process tetanus toxin (TT) or present the TT(830-843) peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-γ to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-γ pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation

Bathymetric Mapping Of The Seafloor - A German Contribution To Completing The Map By 2030, Cruise No. MSM88/1 + MSM88/2, November 28, 2019 - January 14, 2020, Mindelo (Cabo Verde) - Mindelo (Cabo Verde) - Bridgetown (Barbados)

Despite over 100 years of acoustic seabed mapping, only around 15% of the seafloor has ever been directly mapped and little of the mapping performed has been systematic or over larger areas. The result is that our knowledge of seafloor structure is rudimentary and our understanding of the processes which form them has, in principle, advanced little since the advent of plate tectonics. Societally, the seafloor plays a vital role in humanity’s "life support system", for example providing habitat for marine organisms, stimulating mixing of ocean water as part of the overturning circulation system and increasingly being the site of industrial installations. It is scientifically and societally imperative that we bring the level of knowledge of the surface of our planet up to that of bodies like Moon and Mars that are mapped with a resolution better than 100 m per pixel. It is also essential that the data are made freely available to all to support research and conservation. The aim of this cruise was to map previously uncharted part of the tropical Atlantic using the ship’s multibeam system and to provide the data to global open databases as well as to acquire magnetic gradient data along the same tracks. Magnetic anomalies from so-called Oceanic Core Complexes challenged the conventional view that marine magnetic anomalies arose in the upper, extrusive layer of the oceanic crust, because the crust has been stripped away at these complexes. We therefore collected magnetic data simultaneously to the multibeam data in order to constrain the interpretation of the observed seabed morphology

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis

Depletion of CD8+ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8+ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8+ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4+ effector memory T (TEM) cells and, to a lesser extent, transitional memory T (TTrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4+/CCR5+ SIV “target” cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8+ lymphocytes in SIV− RMs led to a sustained increase in the number of potential CD4+ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4+ TEM cell proliferation of CD8+ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4+ TEM and TTrM cell proliferation, it did not recapitulate the viral dynamics of CD8+ lymphocyte depletion. These data suggest that CD8+ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production

Active mud volcanoes on the continental slope of the Canadian Beaufort Sea

The major geochemical characteristics of Red Sea brine are summarized for 11 brine-filled deeps located along the central graben axis between 19°N and 27°N. The major element composition of the different brine pools is mainly controlled by variable mixing situations of halite-saturated solution (evaporite dissolution) with Red Sea deep water. The brine chemistry is also influenced by hydrothermal water/rock interaction, whereas magmatic and sedimentary rock reactions can be distinguished by boron, lithium, and magnesium/calcium chemistry. Moreover, hydrocarbon chemistry (concentrations and δ 13 C data) of brine indicates variable injection of light hydrocarbons from organic source rocks and strong secondary (bacterial or thermogenic) degradation processes. A simple statistical cluster analysis approach was selected to look for similarities in brine chemistry and to classify the various brine pools, as the measured chemical brine compositions show remarkably strong concentration variations for some elements. The cluster analysis indicates two main classes of brine. Type I brine chemistry (Oceanographer and Kebrit Deeps) is controlled by evaporite dissolution and contributions from sediment alteration. The Type II brine (Suakin, Port Sudan, Erba, Albatross, Discovery, Atlantis II, Nereus, Shaban, and Conrad Deeps) is influenced by variable contributions from volcanic/ magmatic rock alteration. The chemical brine classification can be correlated with the sedimentary and tectonic setting of the related depressions. Type I brine-filled deeps are located slightly off-axis from the central Red Sea graben. A typical " collapse structure formation " which has been defined for the Kebrit Deep by evaluating seismic and geomorphological data probably corresponds to our Type I brine. Type II brine located in depressions in the northern Red Sea (i.e., Conrad and Shaban Deeps) could be correlated to " volcanic intrusion-/extrusion-related " deep formation. The chemical indications for hydrothermal influence on Conrad and Shaban Deep brine can be related to brines from the multi-deeps region in the central Red Sea, where volcanic/magmatic fluid/rock interaction is most obvious. The strongest hydrothermal influence is observed in Atlantis II brine (central multi-deeps region), which is also the hottest Red Sea brine body in 2011 (*68.2 °C)

Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses.

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity

A survey of root knot nematodes and resistance to Meloidogyne incognita in sweet potato varieties from Kenyan fields

AbstractThe root knot nematode, Meloidogyne is one of the most economically damaging plant parasitic nematode groups, and are widely distributed in Kenyan agro-ecosystems. The aim of this study was to determine the diversity of Meloidogyne species in Kenyan sweet potato fields and identify sweet potato varieties that exhibit resistance to M. incognita. Meloidogyne species were collected from Nyanza, Western, Eastern and Central Provinces of Kenya. Mitochondrial DNA was used to differentiate Meloidogyne species. The most common species in all sampled regions was M. incognita. Meloidogyne hapla was recorded for the first time in Kenyan sweet potato growing areas (Mosocho, Matayos, Teso South, Manyatta, and Nzaui sub-counties), while M. enterolobii was observed in Kiharu, Matayos and Mosocho sub-counties and a novel Meloidogyne sp. was identified in Kiharu sub-county. Seventy-two sweet potato varieties collected from both agricultural fields and research stations in Kenya were evaluated for resistance to M. incognita under greenhouse conditions in two separate trials. Known susceptible (Beauregard) and resistant (Tanzania) sweet potato varieties were included as controls. Responses of sweet potato varieties to M. incognita infection was assessed by the number of eggs present and level of galling on a scale of 1–5, where 0 = 0 galls and 5 ≥ 100 galls. The reproduction index (RI) was used to classify the varieties as resistant or susceptible. There was a significant difference (P < 0.001) in the number of eggs, GI and RI among the varieties tested. Forty nine sweet potato varieties were considered very resistant and may be used in breeding programs to incorporate resistance against M. incognita into commercial cultivars of sweet potato or to use them in crop rotation programmes for management of RKN. The results on Meloidogyne species diversity in Kenyan sweet potato fields will also be useful in nematode management programs