219 research outputs found
Pseudomonas aeruginosa Adaptation to Lungs of Cystic Fibrosis Patients Leads to Lowered Resistance to Phage and Protist Enemies
Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, Ī¦KZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations
Universality of pseudogap and emergent order in lightly doped Mott insulators
It is widely believed that high-temperature superconductivity in the cuprates
emerges from doped Mott insulators. The physics of the parent state seems
deceivingly simple: The hopping of the electrons from site to site is
prohibited because their on-site Coulomb repulsion U is larger than the kinetic
energy gain t. When doping these materials by inserting a small percentage of
extra carriers, the electrons become mobile but the strong correlations from
the Mott state are thought to survive; inhomogeneous electronic order, a
mysterious pseudogap and, eventually, superconductivity appear. How the
insertion of dopant atoms drives this evolution is not known, nor whether these
phenomena are mere distractions specific to hole-doped cuprates or represent
the genuine physics of doped Mott insulators. Here, we visualize the evolution
of the electronic states of (Sr1-xLax)2IrO4, which is an effective spin-1/2
Mott insulator like the cuprates, but is chemically radically different. Using
spectroscopic-imaging STM, we find that for doping concentration of x=5%, an
inhomogeneous, phase separated state emerges, with the nucleation of pseudogap
puddles around clusters of dopant atoms. Within these puddles, we observe the
same glassy electronic order that is so iconic for the underdoped cuprates.
Further, we illuminate the genesis of this state using the unique possibility
to localize dopant atoms on topographs in these samples. At low doping, we find
evidence for much deeper trapping of carriers compared to the cuprates. This
leads to fully gapped spectra with the chemical potential at mid-gap, which
abruptly collapse at a threshold of around 4%. Our results clarify the melting
of the Mott state, and establish phase separation and electronic order as
generic features of doped Mott insulators.Comment: This version contains the supplementary information and small updates
on figures and tex
Direct Evidence for Dominant Bond-directional Interactions in a Honeycomb Lattice Iridate Na2IrO3
Heisenberg interactions are ubiquitous in magnetic materials and have been
prevailing in modeling and designing quantum magnets. Bond-directional
interactions offer a novel alternative to Heisenberg exchange and provide the
building blocks of the Kitaev model, which has a quantum spin liquid (QSL) as
its exact ground state. Honeycomb iridates, A2IrO3 (A=Na,Li), offer potential
realizations of the Kitaev model, and their reported magnetic behaviors may be
interpreted within the Kitaev framework. However, the extent of their relevance
to the Kitaev model remains unclear, as evidence for bond-directional
interactions remains indirect or conjectural. Here, we present direct evidence
for dominant bond-directional interactions in antiferromagnetic Na2IrO3 and
show that they lead to strong magnetic frustration. Diffuse magnetic x-ray
scattering reveals broken spin-rotational symmetry even above Neel temperature,
with the three spin components exhibiting nano-scale correlations along
distinct crystallographic directions. This spin-space and real-space
entanglement directly manifests the bond-directional interactions, provides the
missing link to Kitaev physics in honeycomb iridates, and establishes a new
design strategy toward frustrated magnetism.Comment: Nature Physics, accepted (2015
Coexistence of metallic and nonmetallic properties in the pyrochlore Lu2Rh2O7
Transition metal oxides of the and block have recently become the
targets of materials discovery, largely due to their strong spin-orbit coupling
that can generate exotic magnetic and electronic states. Here we report the
high pressure synthesis of LuRhO, a new cubic pyrochlore oxide
based on Rh and characterizations via thermodynamic, electrical
transport, and muon spin relaxation measurements. Magnetic susceptibility
measurements reveal a large temperature-independent Pauli paramagnetic
contribution, while heat capacity shows an enhanced Sommerfeld coefficient,
= 21.8(1) mJ/mol-Rh K. Muon spin relaxation measurements confirm
that LuRhO remains paramagnetic down to 2 K. Taken in combination,
these three measurements suggest that LuRhO is a correlated
paramagnetic metal with a Wilson ratio of . However, electric
transport measurements present a striking contradiction as the resistivity of
LuRhO is observed to monotonically increase with decreasing
temperature, indicative of a nonmetallic state. Furthermore, although the
magnitude of the resistivity is that of a semiconductor, the temperature
dependence does not obey any conventional form. Thus, we propose that
LuRhO may belong to the same novel class of non-Fermi liquids as
the nonmetallic metal FeCrAs.Comment: 11 pages, 5 figure
Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation
Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ĪrimK and Īhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome
The protective effect of helmet use in motorcycle and bicycle accidents: a propensity scoreāmatched study based on a trauma registry system
Three-dimensional kinematic motion analysis of a daily activity drinking from a glass: a pilot study
BACKGROUND: Development of reliable and objective evaluation methods is required, particularly for natural and goal-oriented upper-extremity tasks. Three-dimensional imaging measurement techniques have turned out to be a powerful tool for a quantitative and qualitative assessment of multijoint movements. The purpose of this study was to develop and test a method of three-dimensional motion analysis for the activity "drinking from a glass" and describe the drinking task with kinematic variables in control subjects. METHODS: A protocol was developed for the drinking activity including the set-up of cameras and positions of the markers and the subject. The drinking task included reaching, forward transport with glass, drinking, back transport and returning the hand to the initial position. An optoelectronic system was used for the three-dimensional kinematic motion capture. Movement times, velocities, joint angles and interjoint coordination for shoulder and elbow were computed and analyzed for twenty control subjects. Test-retest consistency was evaluated for six subjects. RESULTS: The test protocol showed good consistency in test-retest. Phase definitions for the drinking task were defined and verified. Descriptive kinematic variables were obtained for movement times, positions, velocities and joint angles for shoulder and elbow joint. Interjoint coordination between shoulder and elbow joint in reaching phase showed a high correlation. CONCLUSION: This study provides a detailed description of the three-dimensional kinematic analysis of the drinking task. Our approach to investigate and analyze a goal-oriented daily activity has a great clinical potential. Consequently, the next step is to use and test this protocol on persons with impairments and disabilities from upper extremities
Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer
<p>Abstract</p> <p>Background</p> <p>Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor, and stimulates growth in prostate cancer cells. The current study is to determine a potential role of Vav3 oncogene in human breast cancer and impact on estrogen receptor a (ERĪ±)-mediated signaling axis.</p> <p>Methods</p> <p>Immunohistochemistry analysis was performed in 43 breast cancer specimens and western blot analysis was used for human breast cancer cell lines to determine the expression level of Vav3 protein. The impact of Vav3 on breast cancer cell growth was determined by siRNA knockdown of Vav3 expression. The role of Vav3 in ERĪ± activation was examined in luciferase reporter assays. Deletion mutation analysis of Vav3 protein was performed to localize the functional domain involved in ERĪ± activation. Finally, the interaction of Vav3 and ERĪ± was assessed by GST pull-down analysis.</p> <p>Results</p> <p>We found that Vav3 was overexpressed in 81% of human breast cancer specimens, particularly in poorly differentiated lesions. Vav3 activated ERĪ± partially via PI3K-Akt signaling and stimulated growth of breast cancer cells. Vav3 also potentiated EGF activity for cell growth and ERĪ± activation in breast cancer cells. More interestingly, we found that Vav3 complexed with ERĪ±. Consistent with its function for AR, the DH domain of Vav3 was essential for ERĪ± activation.</p> <p>Conclusion</p> <p>Vav3 oncogene is overexpressed in human breast cancer. Vav3 complexes with ERĪ± and enhances ERĪ± activity. These findings suggest that Vav3 overexpression may aberrantly enhance ERĪ±-mediated signaling axis and play a role in breast cancer development and/or progression.</p
Mediators of the relationship between attachment and dispositional mindfulness in adolescents
Entrapment neuropathy results in different microRNA expression patterns from denervation injury in rats
<p>Abstract</p> <p>Background</p> <p>To compare the microRNA (miRNA) expression profiles in neurons and innervated muscles after sciatic nerve entrapment using a non-constrictive silastic tube, subsequent surgical decompression, and denervation injury.</p> <p>Methods</p> <p>The experimental L4-L6 spinal segments, dorsal root ganglia (DRGs), and soleus muscles from each experimental group (sham control, denervation, entrapment, and decompression) were analyzed using an Agilent rat miRNA array to detect dysregulated miRNAs. In addition, muscle-specific miRNAs (miR-1, -133a, and -206) and selectively upregulated miRNAs were subsequently quantified using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR).</p> <p>Results</p> <p>In the soleus muscles, 37 of the 47 miRNAs (13.4% of the 350 unique miRNAs tested) that were significantly downregulated after 6 months of entrapment neuropathy were also among the 40 miRNAs (11.4% of the 350 unique miRNAs tested) that were downregulated after 3 months of decompression. No miRNA was upregulated in both groups. In contrast, only 3 miRNAs were upregulated and 3 miRNAs were downregulated in the denervated muscle after 6 months. In the DRGs, 6 miRNAs in the entrapment group (miR-9, miR-320, miR-324-3p, miR-672, miR-466b, and miR-144) and 3 miRNAs in the decompression group (miR-9, miR-320, and miR-324-3p) were significantly downregulated. No miRNA was upregulated in both groups. We detected 1 downregulated miRNA (miR-144) and 1 upregulated miRNA (miR-21) after sciatic nerve denervation. We were able to separate the muscle or DRG samples into denervation or entrapment neuropathy by performing unsupervised hierarchal clustering analysis. Regarding the muscle-specific miRNAs, real-time RT-PCR analysis revealed an ~50% decrease in miR-1 and miR-133a expression levels at 3 and 6 months after entrapment, whereas miR-1 and miR-133a levels were unchanged and were decreased after decompression at 1 and 3 months. In contrast, there were no statistical differences in the expression of miR-206 during nerve entrapment and after decompression. The expression of muscle-specific miRNAs in entrapment neuropathy is different from our previous observations in sciatic nerve denervation injury.</p> <p>Conclusions</p> <p>This study revealed the different involvement of miRNAs in neurons and innervated muscles after entrapment neuropathy and denervation injury, and implied that epigenetic regulation is different in these two conditions.</p
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