Sinking properties of some phytoplankton shapes and the relation of form resistance to morphological diversity of plankton – an experimental study

Form resistance (Phi) is a dimensionless number expressing how much slower or faster a particle of any form sinks in a fluid medium than the sphere of equivalent volume. Form resistance factors of PVC models of phytoplankton sinking in glycerin were measured in a large aquarium (0.6 x 0.6 x 0.95 m). For cylindrical forms, a positive relationship was found between Phi and length/ width ratio. Coiling decreased Phi in filamentous forms. Form resistance of Asterionella colonies increased from single cells up to 6-celled colonies than remained nearly constant. For Fragilaria crotonensis chains, no such upper limit to Phi was observed in chains of up to 20 cells ( longer ones were not measured). The effect of symmetry on Phi was tested in 1 - 6-celled Asterionella colonies, having variable angles between the cells, and in Tetrastrum staurogeniaeforme coenobia, having different spine arrangements. In all cases, symmetric forms had considerably higher form resistance than asymmetric ones. However, for Pediastrum coenobia with symmetric/asymmetric fenestration, no difference was observed with respect to symmetry. Increasing number and length of spines on Tetrastrum coenobia substantially increased Phi. For a series of Staurastrum forms, a significant positive correlation was found between arm-length/cell-width ratio and Phi: protuberances increased form resistance. Flagellates (Rhodomonas, Gymnodinium) had a Phi 1. The highest value ( Phi = 8.1) was established for a 20-celled Fragilaria crotonensis chain. Possible origin of the so-called 'vital component' ( a factor that shows how much slower viable populations sink than morphologically similar senescent or dead ones) is discussed, as is the role of form resistance in evolution of high diversity of plankton morphologies

Morphological and Structural Aspects of the Extremely Halophilic Archaeon Haloquadratum walsbyi

Ultrathin square cell Haloquadratum walsbyi from the Archaea domain are the most abundant microorganisms in the hypersaline water of coastal salterns and continental salt lakes. In this work, we explore the cell surface of these microorganisms using amplitude-modulation atomic-force microscopy in nearly physiological conditions. We demonstrate the presence of a regular corrugation with a periodicity of 16–20 nm attributed to the surface layer (S-layer) protein lattice, striped domains asymmetrically distributed on the cell faces and peculiar bulges correlated with the presence of intracellular granules. Besides, subsequent images of cell evolution during the drying process indicate the presence of an external capsule that might correspond to the giant protein halomucin, predicted by the genome but never before observed by other microscopy studies

Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function

INTRODUCTION: Genome-wide association studies link susceptibility to late-onset Alzheimer's disease (LOAD) with EphA1. Sequencing identified a non-synonymous substitution P460L as a LOAD risk variant. Other Ephs regulate vascular permeability and immune cell recruitment. We hypothesized that P460L dysregulates EphA1 receptor activity and impacts neuroinflammation. METHODS: EphA1/P460L receptor activity was assayed in isogenic Human Embryonic Kidney (HEK) cells. Soluble EphA1/P460L (sEphA1/sP460L) reverse signaling in brain endothelial cells was assessed by T-cell recruitment and barrier function assays. RESULTS: EphA1 and P460L were expressed in HEK cells, but membrane and soluble P460L were significantly reduced. Ligand engagement induced Y781 phosphorylation of EphA1 but not P460L. sEphA1 primed brain endothelial cells for increased T-cell recruitment; however, sP460L was less effective. sEphA1 decreased the integrity of the brain endothelial barrier, while sP460L had no effect. DISCUSSION: These findings suggest that P460L alters EphA1-dependent forward and reverse signaling, which may impact blood-brain barrier function in LOAD. Highlights: EphA1-dependent reverse signaling controls recruitment of T cells by brain endothelial cells. EphA1-dependent reverse signaling remodels brain endothelial cell contacts. LOAD-associated P460L variant of EphA1 shows reduced membrane expression and reduced ligand responses. LOAD-associated P460L variant of EphA1 fails to reverse signal to brain endothelial cells.Neuroscience and Mental Health Research Institute (NMHRI), Cardiff University and Sir Geraint Evans Cardiovascular Fund, Cardiff University (grant to A.A. and A.J.R.), L.E.T. by UK Dementia Research Institute, Cardiff University, O.R.M. by School of Medicine, Cardiff University, S.S. and C.L.T. by Eli Lilly (grant to J.W. and A.A.), and C.C. by School of Cellular and Molecular Medicine, University of Bristol. The Bioflux 200 was funded by the Leukemia Research Appeal for Wales, and iBright 1500 was funded by the Ser Cymru II programme (grant CU209 to V.K. and Manon Pritch, which was partially funded by Cardiff University and the European Regional Development Fund through the Welsh Government (Grant CU209 to V.K. and Manon Pritchard)

Phenotypic heterogeneity in IGHV-mutated CLL patients has prognostic impact and identifies a subset with increased sensitivity to BTK and PI3Kδ inhibition

The majority of chronic lymphocytic leukemia (CLL) patients are diagnosed with early-stage disease but the currently used prognostic tools appear to be less informative in this group of patients.1 This is especially problematic for patients with mutated immunoglobulin genes (M-CLL) as they have a more diverse clinical course when compared with patients with unmutated immunoglobulin genes (U-CLL).1, 2, 3, 4 Given the emergence of promising targeted, less toxic, therapeutics in CLL,5, 6 there is an increased need to identify patients who might benefit from early treatment with these new agents

Control of primary productivity and the significance of photosynthetic bacteria in a meromictic kettle lake.

During 1986 planktonic primary production and controlling factors were investigated in a small (A0 = 11.8 · 103 m2, Zmax = 11.5 m) meromictic kettle lake (Mittlerer Buchensee). Annual phytoplankton productivity was estimated to ca 120 gC · m–2 · a–1 (1,42 tC · lake–1 · a–1). The marked thermal stratification of the lake led to irregular vertical distributions of chlorophylla concentrations (Chla) and, to a minor extent, of photosynthesis (Az). Between the depths of 0 to 6 m low Chla concentrations (< 7 mg · m–3) and comparatively high background light attenuation (kw = 0,525 m–1, 77% of total attenuation due to gelbstoff and abioseston) was found. As a consequence, light absorption by algae was low (mean value 17,4%) and self-shading was absent. Because of the small seasonal variation of Chla concentrations, no significant correlation between Chla and areal photosynthesis (A) was observed. Only in early summer (June–July) biomass appears to influence the vertical distribution of photosynthesis on a bigger scale. Around 8 m depth, low-light adapted algae and phototrophic bacteria formed dense layers. Due to low ambient irradiances, the contribution of these organisms to total primary productivity was small. Primary production and incident irradiance were significantly correlated with each other (r2 = 0.68). Although the maximum assimilation number (Popt) showed a clear dependence upon water temperature (Q10 = 2.31), the latter was of minor importance to areal photosynthesis

Repurposing rapid diagnostic tests to detect falsified vaccines in supply chains

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global ‘Prevent, Detect and Respond’ strategy

Innovative method for rapid detection of falsified COVID-19 vaccines through unopened vials using handheld Spatially Offset Raman Spectroscopy (SORS)

Preventing, detecting, and responding to substandard and falsified vaccines is of critical importance for ensuring the safety, efficacy, and public trust in vaccines. This is of heightened importance in context of public health crisis, such as the COVID-19 pandemic, in which extreme world-wide shortages of vaccines provided a fertile ground for exploitation by falsifiers. Here, a proof-of-concept study explored the feasibility of using a handheld Spatially Offset Raman Spectroscopy (SORS) device to authenticate COVID-19 vaccines through rapid analysis of unopened vaccine vials. The results show that SORS can verify the chemical identity of dominant excipients non-invasively through vaccine vial walls. The ability of SORS to identify potentially falsified COVID-19 vaccines was demonstrated by measurement of surrogates for falsified vaccines contained in vaccine vials. In all cases studied, the SORS technique was able to differentiate between surrogate samples from the genuine COVISHIELD™ vaccine. The genuine vaccines tested included samples from six batches across two manufacturing sites to account for any potential variations between batches or manufacturing sites. Batch and manufacturing site variations were insignificant. In conjunction with existing security features, for example on labels and packaging, SORS provided an intrinsic molecular fingerprint of the dominant excipients of the vaccines. The technique could be extended to other COVID-19 and non-COVID-19 vaccines, as well as other liquid medicines. As handheld and portable SORS devices are commercially available and widely used for other purposes, such as airport security, they are rapidly deployable non-invasive screening tools for vaccine authentication.</p

High Chromosome Number in hematological cancer cell lines is a Negative Predictor of Response to the inhibition of Aurora B and C by GSK1070916

<p>Abstract</p> <p>Background</p> <p>Aurora kinases play critical roles in mitosis and are being evaluated as therapeutic targets in cancer. GSK1070916 is a potent, selective, ATP competitive inhibitor of Aurora kinase B and C. Translation of predictive biomarkers to the clinic can benefit patients by identifying the tumors that are more likely to respond to therapies, especially novel inhibitors such as GSK1070916.</p> <p>Methods</p> <p>59 Hematological cancer-derived cell lines were used as models for response where <it>in vitro </it>sensitivity to GSK1070916 was based on both time and degree of cell death. The response data was analyzed along with karyotype, transcriptomics and somatic mutation profiles to determine predictors of response.</p> <p>Results</p> <p>20 cell lines were sensitive and 39 were resistant to treatment with GSK1070916. High chromosome number was more prevalent in resistant cell lines (p-value = 0.0098, Fisher Exact Test). Greater resistance was also found in cell lines harboring polyploid subpopulations (p-value = 0.00014, Unpaired t-test). A review of NOTCH1 mutations in T-ALL cell lines showed an association between NOTCH1 mutation status and chromosome number (p-value = 0.0066, Fisher Exact Test).</p> <p>Conclusions</p> <p>High chromosome number associated with resistance to the inhibition of Aurora B and C suggests cells with a mechanism to bypass the high ploidy checkpoint are resistant to GSK1070916. High chromosome number, a hallmark trait of many late stage hematological malignancies, varies in prevalence among hematological malignancy subtypes. The high frequency and relative ease of measurement make high chromosome number a viable negative predictive marker for GSK1070916.</p

Diversity of Haloquadratum and other haloarchaea in three, geographically distant, Australian saltern crystallizer ponds

Haloquadratum walsbyi is frequently a dominant member of the microbial communities in hypersaline waters. 16S rRNA gene sequences indicate that divergence within this species is very low but relatively few sites have been examined, particularly in the southern hemisphere. The diversity of Haloquadratum was examined in three coastal, but geographically distant saltern crystallizer ponds in Australia, using both culture-independent and culture-dependent methods. Two 97%-OTU, comprising Haloquadratum- and Halorubrum-related sequences, were shared by all three sites, with the former OTU representing about 40% of the sequences recovered at each site. Sequences 99.5% identical to that of Hqr. walsbyi C23T were present at all three sites and, overall, 98% of the Haloquadratum-related sequences displayed ≤2% divergence from that of the type strain. While haloarchaeal diversity at each site was relatively low (9–16 OTUs), seven phylogroups (clones and/or isolates) and 4 different clones showed ≤90% sequence identity to classified taxa, and appear to represent novel genera. Six of these branched together in phylogenetic tree reconstructions, forming a clade (MSP8-clade) whose members were only distantly related to classified taxa. Such sequences have only rarely been previously detected but were found at all three Australian crystallizers