TCR Translocations at the Normal-malignant T Cell Interface

Hematopoiesis is the process leading to production and maturation of peripheral blood cells. All blood cells are derived from hematopoietic stem cells (HSCs) which reside in hematopoietic organs. In mammals, the site of hematopoiesis changes during development, which is sequentially taking place in different organs starting with primitive erythrocytes in the yolk sac, the aorta-gonad mesonephros (AGM) region, the fetal lever, and finally the bone marrow (BM) during adulthood. Blood cells are short-lived, and with a daily demand for more than a billion new hematopoietic cells, a continuous replenishment of progenitor cells committed to specific hematopoietic lineages is required. HSCs are at the top of the hematopoietic hierarchy, and are the only source of progenitors. HSCs comprise 0.005-0.01% of the bone marrow, and their unique properties, i.e. the ability of self-renewal and multi-lineage differentiation potential in combination with a specific stem cell microenvironment/ niche, enable these cells to sustain the hematopoietic system. These cells differentiate into progenitor cells, either into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP), which in due course differentiate into mature blood cells, providing cells to the myeloid or lymphoid system respectively 6. CLPs carry the potential to give rise to B cells, T cells (via the thymus) and NK cells, whereas CMPs have the potential to differentiate into erythrocytes, megakaryocytes, macrophages, and granulocytes. Dendritic cells can arise from both progenitor types. The process of hematopoietic lineage determination is tightly regulated by the BM microenvironment’s extrinsic factors, such as growth factors and cytokines mediated by cell-cell interactions, which sustain survival and proliferation of committed cells. Equally important in determining cell fate are the lineage- and cell-type-specific gene expression signatures (intrinsic factors). These signatures are based on the up and down regulation of transcription factors apparently regulated by the epigenetic-micro RNAs regulatory circuit. The strict regulation of both extrinsic and intrinsic signals is of utmost importance, as deregulation of the expression of these factors could result in hematopoietic malignancies such as leukemia or lymphoma. Such deregulation of gene expression is usually caused by irreversible molecular-cytogenetic changes introduced into the genomic DNA sequence. These changes can be caused by mutations, translocations and deletions concerning genes involved in cell cycle, differentiation, proliferation, and self-renewal processes. During the last decade it has become evident that, next to genetic aberrations, epigenetic alterations can also contribute to tumorigenesis, for example through gene silencing due to aberrant methylation.

The seasonal cycle of submesoscale flows

The seasonal cycle of submesoscale flows in the upper ocean is investigated in an idealised model domain analogous to mid-latitude open ocean regions. Submesoscale processes become much stronger as the resolution is increased, though with limited evidence for convergence of the solutions. Frontogenetical processes increase horizontal buoyancy gradients when the mixed layer is shallow in summer, while overturning instabilities weaken the horizontal buoyancy gradients as the mixed layer deepens in winter. The horizontal wavenumber spectral slopes of surface temperature and velocity are steep in summer and then shallow in winter. This is consistent with stronger mixed layer instabilities developing as the mixed layer deepens and energising the submesoscale. The degree of geostrophic balance falls as the resolution is made finer, with evidence for stronger non-linear and high-frequency processes becoming more important as the mixed layer deepens. Ekman buoyancy fluxes can be much stronger than surface cooling and are locally dominant in setting the stratification and the potential vorticity at fronts, particularly in the early winter. Up to 30% of the mixed layer volume in winter has negative potential vorticity and symmetric instability is predicted inside mesoscale eddies as well as in the frontal regions outside of the vortices

Observation of a large lee wave in the Drake Passage

Lee waves are thought to play a prominent role in Southern Ocean dynamics, facilitating a transfer of energy from the jets of the Antarctic Circumpolar Current to microscale, turbulent motions important in water mass transformations. Two EM-APEX profiling floats deployed in the Drake Passage during the Diapycnal and Isopycnal Mixing Experiment (DIMES) independently measured a 120 ± 20-m vertical amplitude lee wave over the Shackleton Fracture Zone. A model for steady EM-APEX motion is developed to calculate absolute vertical water velocity, augmenting the horizontal velocity measurements made by the floats. The wave exhibits fluctuations in all three velocity components of over 15 cm s−1 and an intrinsic frequency close to the local buoyancy frequency. The wave is observed to transport energy and horizontal momentum vertically at respective peak rates of 1.3 ± 0.2 W m−2 and 8 ± 1 N m−2. The rate of turbulent kinetic energy dissipation is estimated using both Thorpe scales and a method that isolates high-frequency vertical kinetic energy and is found to be enhanced within the wave to values of order 10−7 W kg−1. The observed vertical flux of energy is significantly larger than expected from idealized numerical simulations and also larger than observed depth-integrated dissipation rates. These results provide the first unambiguous observation of a lee wave in the Southern Ocean with simultaneous measurements of its energetics and dynamics

The imprint of Southern Ocean overturning on seasonal water mass variability in Drake Passage

Seasonal changes in water mass properties are discussed in thermohaline coordinates from a seasonal climatology and repeat hydrographic sections. The SR1b CTD transects along Drake Passage are used as a case study. The amount of water within temperature and salinity classes and changes therein are used to estimate dia-thermal and dia-haline transformations. These transformations are considered in combination with climatologies of surface buoyancy flux to determine the relative contributions of surface buoyancy fluxes and subsurface mixing to changes in the distribution of water in thermohaline coordinates. The framework developed provides unique insights into the thermohaline circulation of the water masses that are present within Drake Passage, including the erosion of Antarctic Winter Water (AAWW) during the summer months and the interaction between the Circumpolar Deep Waters (CDW) and Antarctic Intermediate Water (AAIW). The results presented are consistent with summertime wind-driven inflation of the CDW layer and deflation of the AAIW layer, and with new AAIW produced in the winter as a mixture of CDW, remnant AAWW, and surface waters. This analysis therefore highlights the role of surface buoyancy fluxes in the Southern Ocean overturning

Distributed optical fibre sensing for high space‐time resolution ocean velocity observations: A case study From a macrotidal channel

Despite significant recent technological advances, oceanographic observations on horizontal scales of meters to a few kilometres prove challenging. Exploiting legacy seafloor cables presents a disruptive prospect to address this gap, as it may provide low-cost sustained observations with high space-time resolution, enabled through novel opto-electronic interrogation of optical fibers within the cables. Here, we demonstrate this approach in a renewable tidal energy cable embedded within a region with a strong barotropic tide. By making remote measurements continuously over 12 hr, we obtain the distributed differential strain experienced by 2 km of offshore cable from a diverse range of oceanic flow processes, with an along-cable resolution of 2.04 m. We successfully identify: (a) nearshore wave breaking and its modulation by changes in water depth; (b) along-cable tidal velocity, shown to be linearly related to the differential strain; and (c) high-frequency motions consistent with 3-dimensional turbulent processes, either of natural origin or from flow-cable interaction. These inferences are supported by nearby conventional measurements of water depth and velocity

Spatial variations in silicate-to-nitrate ratios in Southern Ocean surface waters are controlled in the short term by physics rather than biology

The nutrient composition (high in nitrate but low in silicate) of Subantarctic Mode Water (SAMW) forces diatom scarcity across much of the global surface ocean. This is because diatoms cannot grow without silicate. After formation and downwelling at the Southern Ocean's northern edge, SAMW re-emerges into the surface layers of the mid- and low-latitude oceans, providing a major nutrient source to primary producers in those regions. The distinctive nutrient composition of SAMW originates in the surface waters of the Southern Ocean, from which SAMW is formed. These waters are observed to transition from being rich in both silicate and nitrate in high-latitude areas of the Southern Ocean to being nitrate-rich but silicate-depleted at SAMW formation sites further north. Here we investigate the key controls of this change in nutrient composition with an idealised model, consisting of a chain of boxes linked by a residual (Ekman- and eddy-induced) overturning circulation. Biological processes are modelled on the basis of seasonal plankton bloom dynamics, and physical processes are modelled using a synthesis of outputs from the data-assimilative Southern Ocean State Estimate. Thus, as surface water flows northward across the Southern Ocean toward sites of SAMW formation, it is exposed in the model (as in reality) to seasonal cycles of both biology and physics. Our results challenge previous characterisations of the abrupt northward reduction in silicate-to-nitrate ratios in Southern Ocean surface waters as being predominantly driven by biological processes. Instead, our model indicates that, over shorter timescales (years to decades), physical processes connecting the deep and surface waters of the Southern Ocean (i.e. upwelling and entrainment) exert the primary control on the spatial distribution of surface nutrient ratios

Ocean mixing beneath Pine Island Glacier ice shelf, West Antarctica

Ice shelves around Antarctica are vulnerable to an increase in ocean-driven melting, with the melt rate depending on ocean temperature and the strength of flow inside the ice-shelf cavities. We present measurements of velocity, temperature, salinity, turbulent kinetic energy dissipation rate, and thermal variance dissipation rate beneath Pine Island Glacier ice shelf, West Antarctica. These measurements were obtained by CTD, ADCP, and turbulence sensors mounted on an Autonomous Underwater Vehicle (AUV). The highest turbulent kinetic energy dissipation rate is found near the grounding line. The thermal variance dissipation rate increases closer to the ice-shelf base, with a maximum value found ∼0.5 m away from the ice. The measurements of turbulent kinetic energy dissipation rate near the ice are used to estimate basal melting of the ice shelf. The dissipation-rate-based melt rate estimates is sensitive to the stability correction parameter in the linear approximation of universal function of the Monin-Obukhov similarity theory for stratified boundary layers. We argue that our estimates of basal melting from dissipation rates are within a range of previous estimates of basal melting

Mesoscale eddy dissipation by a “zoo” of submesoscale processes at a western boundary

Mesoscale eddies are ubiquitous dynamical features that tend to propagate westward and disappear along ocean western boundaries. Using a multiscale observational study, we assess the extent to which eddies dissipate via a direct cascade of energy at a western boundary. We analyze data from a ship‐based microstructure and velocity survey, and an 18‐month mooring deployment, to document the dissipation of energy in anticyclonic and cyclonic eddies impinging on the topographic slope east of the Bahamas, in the North Atlantic Ocean. These observations reveal high levels of turbulence where the steep and rough topographic slope modified the intensified northward flow associated with, in particular, anticyclonic eddies. Elevated dissipation was observed both near‐bottom and at mid depths (200–800 m). Near‐bottom turbulence occurred in the lee of a protruding escarpment, where elevated Froude numbers suggest hydraulic control. Energy was also radiated in the form of upward‐propagating internal waves. Elevated dissipation at mid depths occurred in regions of strong vertical shear, where the topographic slope modified the vertical structure of the northward eddy flow. Here, low Richardson numbers and a local change in the isopycnal gradient of potential vorticity (PV) suggest that the elevated dissipation was associated with horizontal shear instability. Elevated mid‐depth dissipation was also induced by topographic steering of the flow. This led to large anticyclonic vorticity and negative PV adjacent to the topographic slope, suggesting that centrifugal instability underpinned the local enhancement in dissipation. Our results provide a mechanistic benchmark for the realistic representation of eddy dissipation in ocean models