Experimental Crossing Confirms Reproductive Isolation between Cryptic Species within Eulimnogammarus verrucosus (Crustacea: Amphipoda) from Lake Baikal

Ancient lakes are known speciation hotspots. One of the most speciose groups in the ancient Lake Baikal are gammaroid amphipods (Crustacea: Amphipoda: Gammaroidea). There are over 350 morphological species and subspecies of amphipods in Baikal, but the extent of cryptic variation is still unclear. One of the most common species in the littoral zone of the lake, Eulimnogammarus verrucosus (Gerstfeldt, 1858), was recently found to comprise at least three (pseudo)cryptic species based on molecular data. Here, we further explored these species by analyzing their mitogenome-based phylogeny, genome sizes with flow cytometry, and their reproductive compatibility. We found divergent times of millions of years and different genome sizes in the three species (6.1, 6.9 and 8 pg), further confirming their genetic separation. Experimental crossing of the western and southern species, which are morphologically indistinguishable and have adjacent ranges, showed their separation with a post-zygotic reproductive barrier, as hybrid embryos stopped developing roughly at the onset of gastrulation. Thus, the previously applied barcoding approach effectively indicated the separate biological species within E. verrucosus. These results provide new data for investigating genome evolution and highlight the need for precise tracking of the sample origin in any studies in this morphospecies.     

Physiological and Pathological Remodeling of Cerebral Microvessels

There is growing evidence that the remodeling of cerebral microvessels plays an important role in plastic changes in the brain associated with development, experience, learning, and memory consolidation. At the same time, abnormal neoangiogenesis, and deregulated regulation of microvascular regression, or pruning, could contribute to the pathogenesis of neurodevelopmental diseases, stroke, and neurodegeneration. Aberrant remodeling of microvesselsis associated with blood–brain barrier breakdown, development of neuroinflammation, inadequate microcirculation in active brain regions, and leads to the dysfunction of the neurovascular unit and progressive neurological deficits. In this review, we summarize current data on the mechanisms of blood vessel regression and pruning in brain plasticity and in Alzheimer’s-type neurodegeneration. We discuss some novel approaches to modulating cerebral remodeling and preventing degeneration-coupled aberrant microvascular activity in chronic neurodegeneration.     

Nutritional Calcium Supply Dependent Calcium Balance,Bone Calcification and Calcium Isotope Ratios in Rats

Serum calcium isotopes (δ^44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ^44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ^44/42Ca_Serum with bone histology are unknown. We analyzed Ca and δ^44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ^44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ^44/42Ca_Bone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ^44/42Ca_Bone was similar in the femora and ribs. At the time of sacrifice, δ^44/42Ca_Serum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ^44/42Ca_Bone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ^44/42Ca in growing rats. δ^44/42Ca_Serum inversely correlated with markers of bone mineralization.     

Plant zero structure and further order reduction of a singular H∞ controller

A new class of reduced‐order controllers is obtained for the H_∞ problem. The reduced‐order controller does not compromise the performance attained by the full‐order controller. Algorithms for deriving reduced‐order H_∞ controllers are presented in both continuous and discrete time. The reduction in order is related to unstable transmission zeros of the subsystem from disturbance inputs to measurement outputs. In the case where the subsystem has no infinite zeros, the resulting order of the H_∞ controller is lower than that of the existing reduced‐order H_∞ controller designs which are based on reduced‐order observer design. Furthermore, the mechanism of the controller order reduction is analysed on the basis of the two‐Riccati equation approach. The structure of the reduced‐order H_∞ controller is investigated. Copyright © 2002 John Wiley & Sons, Ltd.     

Nonlinear Consensus Algorithms with Uncertain Couplings

Distributed algorithms for synchronization and consensus in multi‐agent networks are considered. The agents are assumed to be linear of arbitrary order, the interaction topology may switch, and the couplings are uncertain, assumed only to satisfy certain quadratic constraints. Using the Kalman‐Yakubovich‐Popov lemma and absolute stability theory techniques, consensus criteria for the networks of this type are obtained. These criteria extend a number of known results for agents with special dynamics and are close in spirit to the celebrated circle criterion for the stability of Lurie systems.     

Succinyl Chitosan-Colistin Conjugates as Promising Drug Delivery Systems

The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3–8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130–318 μg/mg. The size of the obtained particles was 100–200 nm, and the ζ-potential varied from −22 to −28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1–0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20–60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics.     

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways

In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.     

Early Postoperative Immunothrombosis of Bioprosthetic Mitral Valve and Left Atrium: A Case Report

A 72-year-old female patient with mixed rheumatic mitral valve disease and persistent atrial fibrillation underwent mitral valve replacement and suffered from a combined thrombosis of the bioprosthetic valve and the left atrium as soon as 2 days post operation. The patient immediately underwent repeated valve replacement and left atrial thrombectomy. Yet, four days later the patient died due to the recurrent prosthetic valve and left atrial thrombosis which both resulted in an extremely low cardiac output. In this patient’s case, the thrombosis was notable for the resistance to anticoagulant therapy as well as for aggressive neutrophil infiltration and release of neutrophil extracellular traps (NETs) within the clot, as demonstrated by immunostaining. The reasons behind these phenomena remained unclear, as no signs of sepsis or contamination of the BHV were documented, although the patient was diagnosed with inherited thrombophilia that could impede the fibrinolysis. The described case highlights the hazard of immunothrombosis upon valve replacement and elucidates its mechanisms in this surgical setting.     

Engineering the Thermoelectrical Properties of PEDOT:PSS by Alkali Metal Ion Effect

Engineering the electrical properties of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS)holds great potential for various applications such a...     

Robust method to provide exponential convergence of model parameters solving linear time-invariant plant identification problem

The scope of this research is a problem of parameters identification of a linear time-invariant plant, which (1) input signal is not frequency-rich, (2) is subjected to initial conditions and external disturbances. The memory regressor extension (MRE) scheme, in which a specially derived differential equation is used as a filter, is applied to solve the above-stated problem. Such a filter allows us to obtain a bounded regressor value, for which a condition of the initial excitation (IE) is met. Using the MRE scheme, the recursive least-squares method with the forgetting factor is used to derive an adaptation law. The following properties have been proved for the proposed approach. If the IE condition is met, then: (1) the parameter error of identification is bounded and converges to zero exponentially (if there are no external disturbances) or to a set (in the case of them) with an adjustable rate, (2) the parameters adaptation rate is a finite value. The above-mentioned properties are mathematically proved and demonstrated via simulation experiments.