RatDEGdb: a knowledge base of differentially expressed genes in the rat as a model object in biomedical research.

The animal models used in biomedical research cover virtually every human disease. RatDEGdb, a knowledge base of the differentially expressed genes (DEGs) of the rat as a model object in biomedical research is a collection of published data on gene expression in rat strains simulating arterial hypertension, age-related diseases, psychopathological conditions and other human afflictions. The current release contains information on 25,101 DEGs representing 14,320 unique rat genes that change transcription levels in 21 tissues of 10 genetic rat strains used as models of 11 human diseases based on 45 original scientific papers.

Yeast zinc cluster transcription factors involved in the switch from fermentation to respiration show interdependency for DNA binding revealing a novel type of DNA recognition.

In budding yeast, fermentation is the most important pathway for energy production. Under low-glucose conditions, ethanol is used for synthesis of this sugar requiring a shift to respiration. This process is controlled by the transcriptional regulators Cat8, Sip4, Rds2 and Ert1.

Antibiotic resistance gene sequencing is necessary to reveal the complex dynamics of immigration from sewers to activated sludge.

Microbial community composition has increasingly emerged as a key determinant of antibiotic resistance gene (ARG) content. However, in activated sludge wastewater treatment plants (AS-WWTPs), a comprehensive understanding of the microbial community assembly process and its impact on the persistence of antimicrobial resistance (AMR) remains elusive. An important part of this process is the immigration dynamics (or community coalescence) between the influent and activated sludge.

Pertussis toxin suppresses dendritic cell-mediated delivery of B. pertussis into lung-draining lymph nodes.

The adenylate cyclase (ACT) and the pertussis (PT) toxins of Bordetella pertussis exert potent immunomodulatory activities that synergize to suppress host defense in the course of whooping cough pathogenesis. We compared the mouse lung infection capacities of B. pertussis (Bp) mutants (Bp AC- or Bp PT-) producing enzymatically inactive toxoids and confirm that ACT action is required for maximal bacterial proliferation in the first days of infection, whereas PT action is crucial for persistence of B.

Using diffraction losses of X-rays in a single crystal for determination of its lattice parameters as well as for monochromator calibration.

A way has been developed to measure the unit-cell parameters of a single crystal just from an energy scan with X-rays, even when the exact energy of the X-rays is not well defined due to an error in the pitch angle of the monochromator. The precision of this measurement reaches da/a ∼ 1 × 10. The method is based on the analysis of diffraction losses of the beam, transmitted through a single crystal (the so-called `glitch effect').

Differential expression of 10 genes in the hypothalamus of two generations of rats selected for a reaction to humans.

Individual behavioral differences are due to an interaction of the genotype and the environment. Phenotypic manifestation of aggressive behavior depends on the coordinated expression of gene ensembles. Nonetheless, the identification of these genes and of combinations of their mutual influence on expression remains a difficult task.

Domestication Explains Two-Thirds of Differential-Gene-Expression Variance between Domestic and Wild Animals; The Remaining One-Third Reflects Intraspecific and Interspecific Variation.

Belyaev's concept of destabilizing selection during domestication was a major achievement in the XX century. Its practical value has been realized in commercial colors of the domesticated fox that never occur in the wild and has been confirmed in a wide variety of pet breeds. Many human disease models involving animals allow to test drugs before human testing.

Adenylate Cyclase Toxin Elicits Airway Mucin Secretion through Activation of the cAMP Response Element Binding Protein.

The mucus layer protects airway epithelia from damage by noxious agents. Intriguingly, bacteria provoke massive mucus production by nasopharyngeal epithelia during the initial coryza-like catarrhal stage of human pertussis and the pathogen transmits in mucus-containing aerosol droplets expelled by sneezing and post-nasal drip-triggered cough. We investigated the role of the cAMP-elevating adenylate cyclase (CyaA) and pertussis (PT) toxins in the upregulation of mucin production in infected airway epithelia.

A lacZ reporter with high activity in the human fungal pathogen Candida albicans.

Reporter genes are useful tools to study gene transcription in various organisms. For example, the lacZ gene encoding β-galactosidase has been extensively used as a reporter in bacteria, budding yeast, fruit fly, mouse etc. However, use of this gene in the human fungal pathogen Candida albicans has been limited, probably due to low β-galactosidase activity.

Genes associated with cognitive performance in the Morris water maze: an RNA-seq study.

Learning and memory are among higher-order cognitive functions that are based on numerous molecular processes including changes in the expression of genes. To identify genes associated with learning and memory formation, here, we used the RNA-seq (high-throughput mRNA sequencing) technology to compare hippocampal transcriptomes between mice with high and low Morris water maze (MWM) cognitive performance. We identified 88 differentially expressed genes (DEGs) and 24 differentially alternatively spliced transcripts between the high- and low-MWM-performance mice.

HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis.

Drosophila melanogaster has been a model for multiple human disease conditions, including cancer. Among Drosophila tissues, the eye development is particularly sensitive to perturbations of the embryonic signaling pathways, whose improper activation in humans underlies various forms of cancer. We have launched the HumanaFly project, whereas human genes expressed in breast cancer patients are screened for their ability to aberrate development of the Drosophila eye, hoping to thus identify novel oncogenes.

Binding of RtxA Toxin Depends on Cell Surface Oligosaccharides, but Not on β Integrins.

The Gram-negative coccobacillus is increasingly recognized as an important invasive pediatric pathogen that causes mostly bacteremia and skeletal system infections. secretes an RtxA toxin that belongs to a broad family of the RTX (Repeats in ToXin) cytotoxins produced by bacterial pathogens. Recently, we demonstrated that membrane cholesterol facilitates interaction of RtxA with target cells, but other cell surface structures potentially involved in toxin binding to cells remain unknown.

Continuous Assembly of β-Roll Structures Is Implicated in the Type I-Dependent Secretion of Large Repeat-in-Toxins (RTX) Proteins.

Repeats-in-Toxin (RTX) proteins of Gram-negative bacteria are excreted through the type I secretion system (T1SS) that recognizes non-cleavable C-terminal secretion signals. These are preceded by arrays of glycine and aspartate-rich nonapeptide repeats grouped by four to eight β strands into blocks that fold into calcium-binding parallel β-roll structures. The β-rolls are interspersed by linkers of variable length and sequence and the organization of multiple RTX repeat blocks within large RTX domains remains unknown.

Role of NAD-Modulated Mitochondrial Free Radical Generation in Mechanisms of Acute Brain Injury.

It is commonly accepted that mitochondria represent a major source of free radicals following acute brain injury or during the progression of neurodegenerative diseases. The levels of reactive oxygen species (ROS) in cells are determined by two opposing mechanisms-the one that produces free radicals and the cellular antioxidant system that eliminates ROS. Thus, the balance between the rate of ROS production and the efficiency of the cellular detoxification process determines the levels of harmful reactive oxygen species.

Lake Drainage in Permafrost Regions Produces Variable Plant Communities of High Biomass and Productivity.

Climate warming, increased precipitation, and permafrost thaw in the Arctic are accompanied by an increase in the frequency of full or partial drainage of thermokarst lakes. After lake drainage, highly productive plant communities on nutrient-rich sediments may develop, thus increasing the influencing greening trends of Arctic tundra. However, the magnitude and extent of this process remain poorly understood.

Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme-translocating segment of adenylate cyclase toxin.

The adenylate cyclase toxin-hemolysin (CyaA) and the α-hemolysin (HlyA) of belong to the family of cytolytic pore-forming Repeats in ToXin (RTX) cytotoxins. HlyA preferentially binds the αβ integrin LFA-1 (CD11a/CD18) of leukocytes and can promiscuously bind and also permeabilize many other cells. CyaA bears an N-terminal adenylyl cyclase (AC) domain linked to a pore-forming RTX cytolysin (Hly) moiety, binds the complement receptor 3 (CR3, αβ, CD11b/CD18, or Mac-1) of myeloid phagocytes, penetrates their plasma membrane, and delivers the AC enzyme into the cytosol.

A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans.

Aggressiveness is a hereditary behavioral pattern that forms a social hierarchy and affects the individual social rank and accordingly quality and duration of life. Thus, genome-wide studies of human aggressiveness are important. Nonetheless, the aggressiveness-related genome-wide studies have been conducted on animals rather than humans.

NAD precursor modulates post-ischemic mitochondrial fragmentation and reactive oxygen species generation via SIRT3 dependent mechanisms.

Global cerebral ischemia depletes brain tissue NAD, an essential cofactor for mitochondrial and cellular metabolism, leading to bioenergetics failure and cell death. The post-ischemic NAD levels can be replenished by the administration of nicotinamide mononucleotide (NMN), which serves as a precursor for NAD synthesis. We have shown that NMN administration shows dramatic protection against ischemic brain damage and inhibits post-ischemic hippocampal mitochondrial fragmentation.

Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy.

In diabetic neuropathy, there is activation of axonal and sensory neuronal degeneration pathways leading to distal axonopathy. The nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase enzyme, Sirtuin 1 (SIRT1), can prevent activation of these pathways and promote axonal regeneration. In this study, we tested whether increased expression of SIRT1 protein in sensory neurons prevents and reverses experimental diabetic neuropathy induced by a high fat diet (HFD).

CRL-based ultra-compact transfocator for X-ray focusing and microscopy.

A new ultra-compact transfocator (UCTF) based on X-ray compound refractive lenses (CRLs) is presented. The device can be used to change the number of one- and two-dimensional focusing CRLs by moving the individual parabolic lenses one-by-one independently, thus providing permanent energy and focal-length tunability for scanning and full-field X-ray microscopy applications. The small overall size and light weight of the device allow it to be integrated in any synchrotron beamline, while even simplifying the experimental layout.