Tissue distribution and subcellular localization of the family of Kidney Ankyrin Repeat Domain (KANK) proteins

Kidney Ankyrin Repeat-containing Proteins (KANKs) comprise a family of four evolutionary conserved proteins (KANK1 to 4) that localize to the belt of mature focal adhesions (FAs) where they regulate integrin-mediated adhesion, actomyosin contractility, and link FAs to the cortical microtubule stabilization complex (CMSC). The human KANK proteins were first identified in kidney and have been associated with kidney cancer and nephrotic syndrome. Here, we report the distributions and subcellular localizations of the four Kank mRNAs and proteins in mouse tissues. We found that the KANK family members display distinct and rarely overlapping expression patterns. Whereas KANK1 is expressed at the basal side of epithelial cells of all tissues tested, KANK2 expression is mainly observed at the plasma membrane and/or cytoplasm of mesenchymal cells and KANK3 exclusively in vascular and lymphatic endothelial cells. KANK4 shows the least widespread expression pattern and when present, overlaps with KANK2 in contractile cells, such as smooth muscle cells and pericytes. Our findings show that KANKs are widely expressed in a cell type-specific manner, which suggests that they have cell- and tissue-specific functions

Relating statistics to dynamics in axisymmetric homogeneous turbulence

The structure and the dynamics of homogeneous turbulence are modified by the presence of body forces such that the Coriolis or the buoyancy forces, which may render a wide range of turbulence scales anisotropic. The corresponding statistical characterization of such effects is done in physical space using structure functions, as well as in spectral space with spectra of two-point correlations, providing two complementary viewpoints. In this framework, second-order and third-order structure functions are put in parallel with spectra of two-point second- and third-order velocity correlation functions, using passage relations. Such relations apply in the isotropic case, or for isotropically averaged statistics, which, however, do not reflect the actual more complex structure of anisotropic turbulence submitted to rotation or stratification. This complexity is demonstrated in this paper by orientation-dependent energy and energy transfer spectra produced in both cases by means of a two-point statistical model for axisymmetric turbulence. We show that, to date, the anisotropic formalism used in the spectral transfer statistics is especially well-suited to analyze the refined dynamics of anisotropic homogeneous turbulence, and that it can help in the analysis of isotropically computed third-order structure function statistics often used to characterize anisotropic contexts.Comment: Physica

Collective Modes of Tri-Nuclear Molecules

A geometrical model for tri-nuclear molecules is presented. An analytical solution is obtained provided the nuclei, which are taken to be prolately deformed, are connected in line to each other. Furthermore, the tri-nuclear molecule is composed of two heavy and one light cluster, the later sandwiched between the two heavy clusters. A basis is constructed in which Hamiltonians of more general configurations can be diagonalized. In the calculation of the interaction between the clusters higher multipole deformations are taken into account, including the hexadecupole one. A repulsive nuclear core is introduced in the potential in order to insure a quasi-stable configuration of the system. The model is applied to three nuclear molecules, namely $^{96}$Sr + $^{10}$Be + $^{146}$Ba, $^{108}$Mo + $^{10}$Be + $^{134}$Te and $^{112}$Ru + $^{10}$Be + $^{130}$Sn.Comment: 24 pages, 9 figure

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Molecular targeted therapies in head and neck cancer - An update of recent developements -

Targeted therapies have made their way into clinical practice during the past decade. They have caused a major impact on the survival of cancer patients in many areas of clinical oncology and hematology. Indeed, in some hematologic malignancies, such as chronic myelogenous leukemia or non-Hodgkin's lymphomas, biologicals and antibodies specifically designed to target tumour-specific proteins have revolutionized treatment standards. In solid tumours, new drugs targeting EGF- or VEGF- receptors are now approved and are entering clinical practise for treatment of colon, lung, kidney and other cancers, either alone or in combination with conventional treatment approaches

A systematic review of methods used to study fish in saltmarsh flats

There is a growing body of research highlighting the importance of saltmarshes as habitats for fish for feeding, refuge from predation and reproduction. However, more work is needed on fish on vegetated marsh flats (or surfaces). We reviewed 60 studies that used 21 methods to sample fish assemblages on saltmarsh flats. Drop samplers, fyke nets and pop nets were most frequently employed, with considerably more studies being conducted in graminoid than succulent marsh. Reporting of sampling temporal and tidal details, environmental variables and fish attributes was inconsistent. Most of the papers focussed on one or more of conservation management, comparisons among habitat types, and the use of saltmarsh (including fish activity type or residency status). Important potential areas of research include the relationships between the fish assemblages of saltmarsh flats and coastal fisheries, the effects of invasive plant species and marsh restoration efforts in areas outside the United States, and the potential effects of sea-level rise on vegetated flats as fish habitat. Sampling methods that provide density measures are likely to be most useful for most of this research. Thus, drop samplers and pop nets are an appropriate choice, the former in graminoid saltmarshes and the latter in succulent saltmarshes

German federal-state-wide seroprevalence study of 1st SARS-CoV-2 pandemic wave shows importance of long-term antibody test performance

Background Reliable data on the adult SARS-CoV-2 infection fatality rate in Germany are still scarce. We performed a federal state-wide cross-sectional seroprevalence study named SaarCoPS, that is representative for the adult population including elderly individuals and nursing home residents in the Saarland. Methods Serum was collected from 2940 adults via stationary or mobile teams during the 1st pandemic wave steady state period. We selected an antibody test system with maximal specificity, also excluding seroreversion effects due to a high longitudinal test performance. For the calculations of infection and fatality rates, we accounted for the delays of seroconversion and death after infection. Results Using a highly specific total antibody test detecting anti-SARS-CoV-2 responses over more than 180 days, we estimate an adult infection rate of 1.02% (95% CI: [0.64; 1.44]), an underreporting rate of 2.68-fold (95% CI: [1.68; 3.79]) and infection fatality rates of 2.09% (95% CI: (1.48; 3.32]) or 0.36% (95% CI: [0.25; 0.59]) in all adults including elderly individuals, or adults younger than 70 years, respectively. Conclusion The study highlights the importance of study design and test performance for seroprevalence studies, particularly when seroprevalences are low. Our results provide a valuable baseline for evaluation of future pandemic dynamics and impact of public health measures on virus spread and human health in comparison to neighbouring countries such as Luxembourg or France

Functional and Structural Insights Revealed by Molecular Dynamics Simulations of an Essential RNA Editing Ligase in Trypanosoma brucei

RNA editing ligase 1 (TbREL1) is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD) simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme