Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are central to metastatic aggressiveness and therapy resistance in solid tumors. While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and MET inducers has come into focus recently, and has been implicated in the failure of anti-cancer therapies. Recent experimental studies have shown that some cells can undergo an irreversible EMT depending on the duration of exposure to EMT-inducing signals. While the irreversibility of MET, or equivalently, resistance to EMT, has not been studied in as much detail, evidence supporting such behavior is slowly emerging. Here, we identify two possible mechanisms that can underlie resistance of cells to undergo EMT: epigenetic feedback in ZEB1/GRHL2 feedback loop and stochastic partitioning of biomolecules during cell division. Identifying the ZEB1/GRHL2 axis as a key determinant of epithelial-mesenchymal plasticity across many cancer types, we use mechanistic mathematical models to show how GRHL2 can be involved in both the abovementioned processes, thus driving an irreversible MET. Our study highlights how an isogenic population may contain subpopulation with varying degrees of susceptibility or resistance to EMT, and proposes a next set of questions for detailed experimental studies characterizing the irreversibility of MET/resistance to EMT.
Reproduction in North Atlantic right whales (Eubalaena glacialis)

The reproductive biology of the western North Atlantic right whale population was assessed using photoidentification techniques. From 1980 to 1992, 145 calves were born to 65 identified cows. There was no detectable trend in the number of calves produced per year. Mean age at first parturition was 7.57 years. The reproductively active female pool was static at approximately 51 animals from 1987 to 1992. Gross annual reproductive rate, population growth rate, and mortality rate were estimated to be 4.5, 2.5, and 2.0%, respectively. The population size was estimated to be 295 individuals in 1992. Mean calving interval, based on 86 records, was 3.67 years, significantly longer than the South African right whale population but not different from the Argentine population. There was an indication that calving intervals may be increasing over time, though the trend was not quite statistically significant (P = 0.083). Potential causes for the reduced growth rate of this population are unknown but include anthropo.
Excitatory GABAergic modulation of calyx terminals in the vestibular sensory end organ

GABAergic sources have been identified in the vestibular sensory neuroepithelium, mainly in the supporting cells. However, existence of GABA receptors or any possible GABAergic effects on vestibular nerve afferents has not been investigated. The current study was conducted to determine whether activation of GABA-B receptors affects calyx afferent terminals in the central region of the cristae of the semicircular canals in rats. We used patch clamp recording in P13 – P18 Sprague-Dawley rats of either sex. Application of GABA-B receptor agonist baclofen inhibited voltage activated outward potassium currents. This effect was blocked by selective GABA-B receptor antagonist CGP 35348. Antagonists of small (SK) and large (BK) current potassium channels resulted in an almost complete block of baclofen effect. The remaining baclofen effect was due to inhibition of voltage gated calcium channels and was blocked by cadmium chloride. Furthermore, baclofen had no effect in the absence of calcium in the extracellular fluid. Inhibition of potassium currents by GABA-B activation resulted in an excitatory effect on calyx terminal action potential firing. While in the control condition calyces could only fire a single action potential during step depolarizations, in the presence of baclofen they fired continuously during steps and a few even showed spontaneous discharge. We also found a decrease in threshold for action potential generation and a decrease in first spike latency during step depolarization. These results provide the first evidence for the presence of GABA-B receptors on calyx terminals, show that their activation results in an unusual excitatory effect and that GABA inputs could be used to modulate calyx response properties.
NuMA interaction with chromatin is vital for proper nuclear architecture in human cells

NuMA is an abundant long-coiled-coil protein that plays a prominent role in spindle organization during mitosis. In interphase, NuMA is localized to the nucleus and hypothesized to control gene expression and chromatin organization. However, because of the prominent mitotic phenotype upon NuMA loss, its precise function in the interphase nucleus remains elusive. Here, we report that NuMA is associated with chromatin in interphase and prophase but released upon nuclear envelope breakdown (NEBD) by the action of Cdk1. We uncovered that NuMA directly interacts with DNA via evolutionarily conserved sequences in its C-terminus. Notably, the expression of the DNA-binding mutant of NuMA affects chromatin decondensation at the mitotic exit, and nuclear shape in interphase. The impact on nuclear shape by mutant NuMA expression is due to its potential to polymerize into high-order fibrillar structures. This study links the chromatin binding ability of NuMA with the maintenance of nuclear shape and architecture, which has a well-studied role in regulating gene expression during development and diseases.
One gene, multiple ecological strategies: A biofilm regulator is a capacitor for sustainable diversity

Significance Many organisms, including bacteria, live in fluctuating environments that require attachment and dispersal. These lifestyle decisions require processing of multiple external signals by several genetic pathways, but how they are integrated is largely unknown. We conducted multiple evolution experiments totaling >20,000 generations with Burkholderia cenocepacia populations grown in a model of the biofilm life cycle and identified parallel mutations in one gene, rpfR, that is a conserved central regulator. Because RpfR has multiple sensor and catalytic domains, different mutations can produce different ecological strategies that can coexist and even increase net growth. This study demonstrates that a single gene may coordinate complex life histories in biofilm-dwelling bacteria and that selection in defined environments can reshape niche breadth by single mutations. Many bacteria cycle between sessile and motile forms in which they must sense and respond to internal and external signals to coordinate appropriate physiology. Maintaining fitness requires genetic networks that have been honed in variable environments to integrate these signals. The identity of the major regulators and how their control mechanisms evolved remain largely unknown in most organisms. During four different evolution experiments with the opportunist betaproteobacterium Burkholderia cenocepacia in a biofilm model, mutations were most frequently selected in the conserved gene rpfR. RpfR uniquely integrates two major signaling systems—quorum sensing and the motile–sessile switch mediated by cyclic-di-GMP—by two domains that sense, respond to, and control the synthesis of the autoinducer cis-2-dodecenoic acid (BDSF). The BDSF response in turn regulates the activity of diguanylate cyclase and phosphodiesterase domains acting on cyclic-di-GMP. Parallel adaptive substitutions evolved in each of these domains to produce unique life history strategies by regulating cyclic-di-GMP levels, global transcriptional responses, biofilm production, and polysaccharide composition. These phenotypes translated into distinct ecology and biofilm structures that enabled mutants to coexist and produce more biomass than expected from their constituents grown alone. This study shows that when bacterial populations are selected in environments challenging the limits of their plasticity, the evolved mutations not only alter genes at the nexus of signaling networks but also reveal the scope of their regulatory functions.
Chylocladia wynnei sp. nov. (Champiaceae, Rhodophyta) from the Mediterranean Sea

A new species, Chylocladia wynnei sp. nov., is described from the Mediterranean Sea. It consists of 2–4 terete, unbranched erect axes, 5–10(–13) mm high, arising from a discoid holdfast. Axes, covered by a thick mucilaginous layer, are hollow throughout. They are divided into segments by monostromatic diaphragms and are constricted at the diaphragms. Axes have a unilayered cortex and longitudinal filaments lining their inner surface; gland cells are cut off from these filaments. Gametophytic plants are dioecious and consist of only two segments. Male thalli have spermatangia in superficial sori located between the two segments. One or two spherical sessile cystocarps are borne on the distal part of the basal segment. Tetrasporic plants comprise 4–5 segments; tetrahedrally divided tetrasporangia are scattered throughout the thallus. These sporangia are transformed from larger cortical cells and, when mature, they protrude into the thallus cavity. Diminutive stature and unbranched erect axes covered with a thick mucilaginous layer clearly distinguish C. wynnei from previously described species of Chylocladia.
Rapid invisible frequency tagging reveals nonlinear integration of auditory and visual information

During communication in real-life settings, the brain integrates information from auditory and visual modalities to form a unified percept of our environment. In the current magnetoencephalography (MEG) study, we used rapid invisible frequency tagging (RIFT) to generate steady-state evoked fields and investigated the integration of audiovisual information in a semantic context. We presented participants with videos of an actress uttering action verbs (auditory; tagged at 61 Hz) accompanied by a gesture (visual; tagged at 68 Hz, using a projector with a 1440 Hz refresh rate). Integration difficulty was manipulated by lower-order auditory factors (clear/degraded speech) and higher-order visual factors (congruent/incongruent gesture). We identified MEG spectral peaks at the individual (61/68 Hz) tagging frequencies. We furthermore observed a peak at the intermodulation frequency of the auditory and visually tagged signals (fvisual - fauditory = 7 Hz), specifically when lower-order integration was easiest because signal quality was optimal. This intermodulation peak is a signature of nonlinear audiovisual integration, and was strongest in left inferior frontal gyrus and left temporal regions; areas known to be involved in speech-gesture integration. The enhanced power at the intermodulation frequency thus reflects the ease of lower-order audiovisual integration and demonstrates that speech-gesture information interacts in higher-order language areas. Furthermore, we provide a proof-of-principle of the use of RIFT to study the integration of audiovisual stimuli, in relation to, for instance, semantic context.
Effects of monoglyceride content, cooling rate and shear on the rheological properties of olive oil/monoglyceride gel networks

Functionality of conventional fat spreads can be achieved without hydrogenation by the formation of stable network structures upon cooling of mixtures of monoglycerides (MGs) and vegetable oils from the melt. Such mixtures are healthy substitutes for margarine and butter. The effects of MG content, cooling rate and shear on the temperature ramp, mechanical spectra and hardness of olive oil/MG gel networks were investigated. A minimum MG volume fraction was necessary for formation of a gelled network, but this concentration was less than that needed for a space-filling network structure. Onset of gel network or structure formation was indicated by a sudden divergence in value of the elastic modulus G � . The temperature at onset of structure formation, To ,fi nalGvalue and network hardness all increased with increase in MG content. High cooling rates led to low final Gvalues but harder networks, and vice versa. Maximum gel network development occurred when moderate shear (about 300s −1 ) was applied at incipient gelation.  2004 Society of Chemical Industry
Side-effects on honeybees

It is important that plant protection products should be authorized for use only in ways which do not pose an unacceptable risk of harm to honeybees (Apis mellifera). For this purpose, it may be necessary to provide evidence during the registration process to enable the safety of the product in question to be evaluated. This standard presents several different types of test (laboratory tests, semi-field cage tests and field trials) which can be used to provide such evidence. The description of these methods is based upon the ‘Recommendations for harmonization of methods for testing hazards of pesticides to honeybees’, decided by the International Commission for Plant–Bee Relationships (ICPBR) at the Symposia on the harmonization of methods for testing the toxicity of pesticides to bees held in Wageningen, NL (1980), Hohenheim, DE (1982), Harpenden, GB (1985), Rez, CZ (1990), Wageningen, NL (1993), Braunschweig, DE (1996), Avignon, FR (1999), Bologna IT (2002), York, GB (2005) and Bucharest, RO (2008). The laboratory tests examine oral toxicity and contact toxicity of the plant protection product. The semi-field cage test and the field trial study the effects of application of the product during bee flight. As well as providing a worst-case assessment under realistic conditions of exposure, the cage test can be designed to study certain hazards to honeybees which are not possible to study by field trials, such as the effects on bees foraging the honeydew from aphids. Laboratory tests are conducted with single bees or groups of bees, while semi-field and field tests are conducted with bee colonies on a crop. While recognizing that no single test method can provide sufficient information to classify the side-effects of plant protection products on honeybees, it is also important to stress that all these tests are not required. Because field testing is time-consuming and costly, the laboratory tests or semi-field test may serve to classify many products as definitely harmless or harmful without having recourse to field trials. The decisions on which tests to perform and on whether to proceed from one test to another will depend on the characteristics of the plant protection product, its use pattern, and the tests already performed. These decisions can be derived from a logically constructed sequential decision-making scheme (Oomen, 1986). A joint EPPO ⁄Council of Europe Panel on Environmental Risk Assessment of Plant Protection Products has developed such schemes, including one for honeybees (OEPP ⁄ EPPO, 1993, 2003, 2010). This guideline is designed to provide sufficient information to allow the appropriate tests to be conducted and evaluated, but also to be sufficiently flexible to accommodate the specific needs of individual tests (Alix & Lewis, 2010).
αA-Crystallin interacting regions in the small heat shock protein, αB-crystallin

Amino acid sequences of alphaB-crystallin, involved in interaction with alphaA-crystallin, were determined by using peptide scans. Positionally addressable 20-mer overlapping peptides, representing the entire sequence of alphaB-crystallin, were synthesized on a PVDF membrane. The membrane was blocked with albumin and incubated with purified alphaA-crystallin. Probing the membrane with alphaA-crystallin-specific antibodies revealed residues 42-57, 60-71, and 88-123 in alphaB-crystallin to interact with alphaA-crystallin. Residues 42-57 and 60-71 interacted more strongly with alphaA-crystallin than the 88-123 sequence of alphaB-crystallin. Binding of one of the alphaB peptides (42-57) to alphaA-crystallin was also confirmed by gel filtration studies and HPLC analysis. The alphaB-crystallin sequences involved in interaction with alphaA-crystallin were distinct from the chaperone sites reported earlier as binding of the alphaB sequence from residues 42-57 does not alter the chaperone-like function of alphaA-crystallin. To identify the critical residues involved in interaction with alphaA-crystallin, R50G and P51A mutants of alphaB-crystallin were made and tested for their ability to interact with alphaA-crystallin. The oligomeric size and hydrophobicity of the mutants were similar. Circular dichroism studies showed that the P51A mutation increased the alpha-helical content of the protein. While the alphaBR50G mutant showed chaperone-like activity similar to wild-type alphaB, alphaBP51A showed reduced chaperone function. Fluorescence resonance energy transfer studies showed that the P51A mutation decreased the rate of subunit exchange with alphaA by 63%, whereas the R50G mutation reduced the exchange rate by 23%. Similar to wild-type alphaB, alphaB-crystallin peptide (42-57) effectively competed with alphaBP51A and alphaBR50G for interaction with alphaA. Thus, our studies showed that the alphaB-crystallin sequence (42-57) is one of the interacting regions in alphaB and alphaA oligomer formation.
The Actin Cytoskeleton and the Regulation of Cell Migration

Abstract Download Free Sample The mammalian cytoskeleton is an internal framework of actin, tubulin, and intermediate filament proteins. Proteins of these three classes assemble non-covalently into filamentous polymers that support the structural integrity of the relatively fragile lipid plasma membrane. In addition, cytoskeletal polymers provide the mechanical strength that hold a cell together and anchor it to its growth substrate. The cytoskeleton must also have the capacity for rapid and substantial remodeling and provide the motive and tractor force necessary to drive motility. As such, the cytoskeleton has a functional duality: sufficiently rigid to prevent plasma membrane deformation but pliable enough to allow for cytokinesis; sufficiently adhesive to allow for traction but dynamic enough to allow movement from one place to another. A major research challenge in cytoskeleton biology is to understand how cytoskeletal proteins assemble and dissemble in support of physiological processes. This chapte.
Molecular markers linked to rhizomania resistance in sugar beet, Beta vulgaris, from two different sources map to the same linkage group

Rhizomania, one of the most important diseases of sugar beet, is caused by beet necrotic yellow vein virus, a Furovirus vectored by the fungus Polymyxa betae Keskin. Reduction of the production losses caused by this disease can only be achieved by using tolerant cultivars. The objective of this study was the identification and mapping of random amplified polymorphic DNA (RAPD) markers linked to a rhizomania resistance gene. The RAPD markers were identified using bulked segregant analysis in a segregating population of 62 individuals derived by intercrossing plants of the resistant commercial hybrid GOLF, and the resistance locus was positioned in a molecular marker linkage map made with a different population of 50 GOLF plants. The resistance locus, Rr1, was mapped to linkage group III of our map of Beta vulgaris L. ssp. vulgaris, which consisted of 76 RAPDs, 20 restriction fragment length polymorphisms (RFLPs), three sequence characterized amplified regions (SCARs) and one sequence tagged site (STS). In total, 101 molecular markers were mapped over 14 linkage groups which spanned 688.4 cM with an average interval length of 8.0 cM. In the combined map, Rr1 proved to be flanked by the RAPD loci RA4111800 and AS71100 at 9.5 and 18.5cM, respectively. Moreover, in our I2 population, we found that a set of markers shown by Barzen et al. (1997) to be linked to the ‘Holly’ type resistance gene was also linked to the ‘GOLF’-type resistance gene. These results appeared to indicate that the rhizomania resistance gene present in the GOLF hybrid could be the same gene underlying resistance in ‘Holly’-based resistant genotypes. Two other explanations could be applied: first, that two different alleles at the same locus could have been selected; second, that two different genes at two different but clustered loci underwent the selection process.
Effects of mechanical treatment of whole canola seeds on performance, diet digestibility and rumen parameters of lambs fed grass silage

Thirty-three lambs (25.2 ± 2.7 kg body weight) were used to determine if mechanical treatment of canola seed could improve the performance of growing lambs and diet digestibility. All lambs received a basal diet of 179 g d−1 of a 16% crude protein (CP) commercial concentrate and grass silage fed ad libitum. The basal diet was supplemented with the following dietary treatments (dry matter basis): C, a control supplement supplying 182 g of a mixture of 66% canola meal and 34% canola oil; WCS, 187 g of whole canola seeds; RCS, 188 g of rolled canola seeds; and GCS, 189 g of ground canola seeds. Dry matter intake was similar for all diets. Average daily gain (ADG) was 20% lower (P < 0.001) for lambs fed whole or crushed canola seeds than for those fed the C diet. Lambs fed GCS had intermediate ADG between those fed C and those fed WCS and RCS diets. In general, apparent digestibility of C was higher (P < 0.01) than that of WCS and RCS and digestibility of GCS was intermediate. Rumen pH and molar proportions o.