Consequences of limited sediment supply for long-term evolution of offshore tidal sand waves, a 3D model perspective

Field data show that offshore tidal sand waves in areas where sediment supply is limited have different characteristics (shape and dimensions) compared with their counterparts in areas with sufficient sediment supply. So far, only the initial formation of tidal sand waves on a sediment-starved shelf has been studied with a 2DV model that ignores variations along the crests. In this study, a 3D non-linear morphodynamic model is used to investigate the effects of sediment availability on the long-term evolution of offshore tidal sand waves. Overall, the simulated sand waves have characteristics that resemble those of observed sand waves. The mature sand waves that develop in the case of limited sediment supply (i.e., thickness of erodible sediment layer is smaller than the height of sand waves) are more three-dimensional, i.e., having isolated and more irregular crestlines compared with those in the case of sufficient supply. With decreasing sediment supply, sand waves have larger spacings between successive crests, smaller heights and they migrate faster. These differences in the characteristics of the sand waves start to occur once the hard bed underneath the erodible sediment layer is exposed

Calcium-activated potassium channels:Implications for aging and age-related neurodegeneration

Population aging, as well as the handling of age-associated diseases, is a worldwide increasing concern. Among them, Alzheimer's disease stands out as the major cause of dementia culminating in full dependence on other people for basic functions. However, despite numerous efforts, in the last decades, there was no new approved therapeutic drug for the treatment of the disease. Calcium-activated potassium channels have emerged as a potential tool for neuronal protection by modulating intracellular calcium signaling. Their subcellular localization is determinant of their functional effects. When located on the plasma membrane of neuronal cells, they can modulate synaptic function, while their activation at the inner mitochondrial membrane has a neuroprotective potential via the attenuation of mitochondrial reactive oxygen species in conditions of oxidative stress. Here we review the dual role of these channels in the aging phenotype and Alzheimer's disease pathology and discuss their potential use as a therapeutic tool

The behavioural assessment of the dysexecutive syndrome as a tool to assess executive functions in schizophrenia

Recent research into the cognitive dysfunctions in schizophrenia has focused on executive deficits. This study investigates performance of patients with schizophrenia on the recently developed Behavourial Assessment of the Dysexecutive Syndrome (BADS). Matched groups of 24 patients with schizophrenia and 17 healthy volunteers were administered the BADS, the Modified Card Sorting Test (MCST), the Tower of London (TOL), a test of general intelligence, and measures of daily functioning. Performance of the schizophrenic group was significantly below that of the control group on the BADS and the MCST, but not on the TOL. The BADS correlated weakly with the MCST. Both tests showed a modest correlation with daily functioning. The BADS appears to offer a useful contribution to the assessment of executive deficits in schizophrenia

Social and non-social reward learning reduced and related to a familial vulnerability in schizophrenia spectrum disorders

Patients with a disorder in the schizophrenia spectrum (SZ) demonstrate impairments in reward learning. A reduced sensitivity to social reward may impede social beyond non-social reward learning mechanisms. The aim of the current study was to investigate social and non-social reward learning in SZ by means of two interactive game-theoretical investment paradigms. Unaffected first-degree relatives of patients were included to examine whether (social) reward-learning impairments are part of a familial vulnerability of SZ. We included 50 patients with a SZ disorder, 20 unaffected first-degree relatives of patients and 49 healthy controls. The trust game (social) and the lottery game (non-social) were used, consisting of 20 game trials each. The game paradigms were programmed to increase the likelihood of higher repayments in response to increased investments. Multilevel regression analyses were used to examine learning over trials in both contexts. The results showed that controls learned equally well in social and non-social contexts, as reflected in an increase of investments over game rounds in both paradigms. In contrast, patients and relatives showed reduced reward learning, regardless of its social or non-social nature, reflected by flatter or decreasing slopes over game rounds in both paradigms. The findings suggest that patients and relatives have a general reduced sensitivity to reward, which appears to reflect a familial vulnerability rather than illness related mechanisms. Results indicate that reward learning may be an important marker for the familial risk to SZ

GATA2 haploinsufficient patients lack innate lymphoid cells that arise after hematopoietic cell transplantation.

Innate lymphoid cells (ILC) are important barrier tissue immune regulators. They play a pivotal role in early non-specific protection against infiltrating pathogens, regulation of epithelial integrity, suppression of pro-inflammatory immune responses and shaping the intestinal microbiota. GATA2 haploinsufficiency causes an immune disorder that is characterized by bone marrow failure and (near) absence of monocytes, dendritic cells, B cells and natural killer (NK) cells. T cells develop normally, albeit at lower numbers. Here, we describe the absence of ILCs and their progenitors in blood and bone marrow of two patients with GATA2 haploinsufficiency and show that all subsets of ILCs appear after allogeneic hematopoietic stem cell transplantation, irrespective of the preparative conditioning regimen. Our data indicate that GATA2 is involved in the development of hematopoietic precursor cells (HPC) towards the ILC lineage

Tectonic Transport Directions, Shear Senses and Deformation Temperatures Indicated by Quartz c‐Axis Fabrics and Microstructures in a NW‐SE Transect across the Moine and Sgurr Beag Thrust Sheets, Caledonian Orogen of Northern Scotland

Moine metasedimentary rocks of northern Scotland are characterized by arcuate map patterns of mineral lineations that swing progressively clockwise from orogen‐perpendicular E‐trend-ing lineations in greenschist facies mylonites above the Moine thrust on the foreland edge of the Caledonian Orogen, to S‐trending lineations at higher structural levels and metamorphic grades in the hinterland. Quartz c‐axis fabrics measured on a west to east coast transect demonstrate that the lineations developed parallel to the maximum principal extension direction and therefore track the local tectonic transport direction. Microstructures and c‐axis fabrics document a progressive change from top to the N shearing in the hinterland to top to the W shearing on the foreland edge. Field relationships indicate that the domain of top to the N shearing was at least 55 km wide before later horizontal shortening on km‐scale W‐vergent folds that detach on the underlying Moine thrust. Previously published data from the Moine thrust mylonites demonstrate that top to the W shearing had largely ceased by 430 Ma, while preliminary isotopic age data suggest top to the N shearing occurred at ~470–450 Ma. In addition, data from the east coast end of our transect indicate normal-sense top down‐SE shearing at close to peak temperatures at ~420 Ma that may be related to the closing stages of Scandian deformation, metamorphism and cooling/exhumation

Thermobarometry of the Moine and Sgurr Beag thrust sheets, northern Scotland

In the Caledonides of northern Scotland temperatures of metamorphism (Tm) and deformation (Td) progressively increase structurally up section in the Moine thrust sheet at the foreland edge of the Scandian (mid Silurian) orogenic wedge. However, the thermal history of the structurally overlying, more hinterland positioned thrust sheets is less well known. This study focuses on determining Td and Tm for both the central/upper part of the Moine thrust sheet and the lower part of the overlying Sgurr Beag thrust sheets in the middle of the Northern Highlands Terrane. Preserved microstructures and quartz c-axis fabric opening angles in the Moine and Sgurr Beag thrust sheets imply Td of 460 °C to 605 °C ± 50 °C. Thermobarometry and pseudosection-based P-T constraints, indicate Tm of ∼550–680 °C at 4.8–7.2 kbar in the Moine thrust sheet and Tm of ∼620 °C at 5.6–7.7 kbar in the Sgurr Beag thrust sheet. Together, Td and Tm in the Moine and Sgurr Beag thrust sheets indicate that deformation continued after peak metamorphic conditions in the Sgurr Beag thrust sheet. Monazite and xenotime petrochronology show that Tm, and possibly Td, record Precambrian metamorphism. Peak metamorphism is associated with the Knoydartian orogenic event (840-720 Ma), with possible reworking during Scandian thrusting (430-425 Ma)

SK channel activation potentiates auranofin-induced cell death in glio- and neuroblastoma cells

Brain tumours are among the deadliest tumours being highly resistant to currently available therapies. The proliferative behaviour of gliomas is strongly influenced by ion channel activity. Small-conductance calcium-activated potassium (SK/KCa) channels are a family of ion channels that are associated with cell proliferation and cell survival. A combined treatment of classical anti-cancer agents and pharmacological SK channel modulators has not been addressed yet. We used the gold-derivative auranofin to induce cancer cell death by targeting thioredoxin reductases in combination with CyPPA to activate SK channels in neuro- and glioblastoma cells. Combined treatment with auranofin and CyPPA induced massive mitochondrial damage and potentiated auranofin-induced toxicity in neuroblastoma cells in vitro. In particular, mitochondrial integrity, respiration and associated energy generation were impaired. These findings were recapitulated in patient-derived glioblastoma neurospheres yet not observed in non-cancerous HT22 cells. Taken together, integrating auranofin and SK channel openers to affect mitochondrial health was identified as a promising strategy to increase the effectiveness of anti-cancer agents and potentially overcome resistance