Inhibition of the proteasome and proteaphagy enhances apoptosis in FLT3-ITD-driven acute myeloid leukemia.

Acute myeloid leukaemia (AML) is a clonal disorder that affects hematopoietic stem cells or myeloid progenitors. One of the most common mutations that results in AML occurs in the gene encoding fms-like tyrosine kinase 3 (FLT3). Previous studies have demonstrated that AML cells expressing FLT3-internal tandem duplication (ITD) are more sensitive to the proteasome inhibitor bortezomib (Bz) than FLT3 wild-type cells, with this cytotoxicity being mediated by autophagy (Atg).

Physical models of infant mortality: implications for defects in biological systems.

Reliability engineering concerned with failure of technical inanimate systems usually uses the vocabulary and notions of human mortality, e.g., infant mortality vs.

: A Model for Studying the Extracellular Vesicle Messengers Involved in Human Health and Disease.

Cell-derived extracellular vesicles (EVs) are newly uncovered messengers for intercellular communication. They are released by almost all cell types in the three kingdoms, Archeabacteria, Bacteria and Eukaryotes. They are known to mediate important biological functions and to be increasingly involved in cell physiology and in many human diseases, especially in oncology.

Altered dynamics of neurovascular coupling in CADASIL.

Background And Objective: Neurovascular coupling is the complex biological process that underlies use-dependent increases in blood flow in response to neural activation. Neurovascular coupling was investigated at the early stage of CADASIL, a genetic paradigm of ischemic small vessel disease.

Methods: Functional hyperemia and evoked potentials during 20- and 40-sec visual and motor stimulations were monitored simultaneously using arterial spin labeling-functional magnetic resonance imaging (ASL-fMRI) and electroencephalography.

A 4.5-Year Within-Patient Evolution of a Colistin-Resistant Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Sequence Type 258.

Background: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) has emerged globally over the last decade as a major nosocomial pathogen that threatens patient care. These highly resistant bacteria are mostly associated with a single Kp clonal group, CG258, but the reasons for its host and hospital adaptation remain largely unknown.

Can monolinguals be like bilinguals? Evidence from dialect switching.

Bilinguals rely on cognitive control mechanisms like selective activation and inhibition of lexical entries to prevent intrusions from the non-target language. We present cross-linguistic evidence that these mechanisms also operate in bidialectals. Thirty-two native German speakers who sometimes use the Öcher Platt dialect, and thirty-two native English speakers who sometimes use the Dundonian Scots dialect completed a dialect-switching task.

Evolutionary Lessons from Species with Unique Kinetochores.

The kinetochore is the multi-protein complex that drives chromosome segregation in eukaryotes. It assembles onto centromeric DNA and mediates attachment to spindle microtubules. Kinetochore research over the last several decades has been focused on a few animal and fungal model organisms, which revealed a detailed understanding of the composition and organization of their kinetochores.

Masked Morphological Priming in German-Speaking Adults and Children: Evidence from Response Time Distributions.

In this study, we looked at masked morphological priming effects in German children and adults beyond mean response times by taking into account response time distributions. We conducted an experiment comparing suffixed word primes (kleidchen-KLEID), suffixed nonword primes (kleidtum-KLEID), nonsuffixed nonword primes (kleidekt-KLEID), and unrelated controls (träumerei-KLEID). The pattern of priming in adults showed facilitation from suffixed words, suffixed nonwords, and nonsuffixed nonwords relative to unrelated controls, and from both suffixed conditions relative to nonsuffixed nonwords, thus providing evidence for morpho-orthographic and embedded stem priming.

Unilateral blood flow decrease induces bilateral and symmetric responses in the immature brain.

The effects of hemodynamic changes in the developing brain have yet to be fully understood. The aim of this study was to explore the relationship between perturbations of the cerebral blood flow in the developing brain via unilateral hypoperfusion in P7 rats. As expected, nuclear caspase-3 (casp3) cleavage and DNA fragmentation were detected at 48 hours after stroke in the injured cortex.

The rational design of biological complexity: a deceptive metaphor.

Biologists often claim that they follow a rational design strategy when their research is based on molecular knowledge of biological systems. This claim implies that their knowledge of the innumerable causal connections present in biological systems is sufficient to allow them to deduce and predict the outcome of their experimental interventions. The design metaphor is shown to originate in human intentionality and in the anthropomorphic fallacy of interpreting objects, events, and the behavior of all living organisms in terms of goals and purposes.

A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.

We report the natural history of a hypopituitarism in a large Tunisian kindred including 29 subjects from the same consanguineous family. The index case was a 9-yr-old girl with severe growth retardation due to complete GH deficiency and partial corticotroph, lactotroph, and thyrotroph deficiencies. Magnetic resonance imaging showed a hyperplastic anterior pituitary.

Enhanced spatiotemporal laser-beam smoothing in gas-jet plasmas.

Spatiotemporal smoothing of large-scale laser intensity fluctuations is observed for a laser beam focused into underdense helium plasmas. This smoothing is found to be severely enhanced when focusing the laser beam into a helium gas jet. In contrast to other experiments with preformed plasmas, the average and the peak laser intensities are well below the threshold for ponderomotive self-focusing.

Priming and activation of mouse macrophages by trehalose 6,6'-dicorynomycolate vesicles from Corynebacterium glutamicum.

Vesicles consisting of pure trehalose dicorynomycolate (TDCM), the corynebacterial analog of the most studied mycobacterial glycolipid 'cord factor', were isolated from Corynebacterium glutamicum cells by mild detergent treatment; these induced in vivo a macrophage priming similar to that obtained with mycobacterial-derived trehalose dimycolate. In vitro, both TDCM and bacterial lipopolysaccharide (LPS) induced in macrophages the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), endotoxin tolerance, and were primed for an enhanced secondary NO response to LPS. Interferon-gamma pretreatment did not influence the LPS-induced TNF-alpha response, but considerably increased the TDCM-induced response.

Antagonistic effects of interferon-gamma and interleukin-4 on fibroblast cultures.

A major characteristic of scleroderma (SSc) fibroblasts is an increased biosynthesis of extracellular matrix macromolecules that could be linked to impaired regulation by cytokines. We investigated the effects of two cytokines from T lymphocytes, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), on normal and scleroderma fibroblast cultures. In both types of fibroblasts, IL-4 strongly stimulated collagen synthesis, whereas IFN-gamma was a potent inhibitor.

Differential involvement of disulfide bridges on the folding of a scorpion toxin.

Leiurotoxin I is a neurotoxin, blocker of Ca(2+)-activated apamin-sensitive K+ channel, purified from the venom of the scorpion Leiurus quinquestriatus hebraeus. It is a 31-residue polypeptide reticulated by three disulfide bridges, i.e.

Role of zinc-binding- and hemopexin domain-encoded sequences in the substrate specificity of collagenase and stromelysin-2 as revealed by chimeric proteins.

The relationship of enzyme structure to substrate specificity for the matrix metalloproteinases interstitial collagenase and stromelysin-2 has been investigated by analysis of the cleavage specificity of recombinant human collagenase-stromelysin-2 hybrid proteins and C terminally truncated collagenase and stromelysin-2. Two series of chimeric proteins were devised by progressive substitution of exon-encoded domains. The recombinant proteins were expressed in COS-7 cells as protein A-fusion proteins and purified on an IgG affinity matrix.

Incorporation of Paramecium axonemal tubulin into higher plant cells reveals functional sites of microtubule assembly.

Incorporation of Paramecium axonemal tubulin into lysed endosperm cells of the higher plant Haemanthus enabled us to identify sites of microtubule assembly. This exogenous Paramecium tubulin could be traced by specific antibodies that do not stain endogenous plant microtubules. Intracellular copolymerization of protozoan and higher plant tubulins gave rise to hybrid polymers that were visualized by immunofluorescence and by immunoelectron microscopy.

[Genetic analysis of the hybridization zone between two subspecies Mus musculus domesticus and Mus musculus musculus in Bulgaria].

The hybrid zone between the two subspecies of mice Mus musculus domesticus and Mus musculus musculus, which has been studied extensively in Denmark, crosses Europe to the Black Sea through the Alps and the Balkans. Two hundred and seventy-nine animals were captured in 22 localities along a transect across the Balkans. The animals were characterized for seven diagnostic nuclear loci by protein electrophoresis and by restriction pattern analysis of their mitochondrial DNA.