4,321 research outputs found
Emergence and development of H7N9 influenza viruses in China
The occurrence of human infections with avian H7N9 viruses since 2013 demonstrates the continuing pandemic threat posed by the current influenza ecosystem in China. Influenza surveillance and phylogenetic analyses showed that these viruses were generated by multiple interspecies transmissions and reassortments among the viruses resident in domestic ducks and the H9N2 viruses enzootic in chickens. A large population of domestic ducks hosting diverse influenza viruses provided the precondition for these events to occur, while acquiring internal genes from enzootic H9N2 influenza viruses in chickens promoted the spread of these viruses. Human infections effectively act as sentinels, reflecting the intensity of the activity of these viruses in poultry.postprin
Extra-hepatic fascioliasis with peritoneal malignancy tumor feature
Fascioliasis is a zoonose parasitic disease
caused by Fasciola hepatica and Fasciola gigantica and is
widespread in most regions of the world. Ectopic fascioliasis
usually caused by juvenile Fasciola spp., but in
recent years a few cases of tissue-embedded ova have been
reported from different endemic areas. A 79-year-old Iranian
man resident in Eird-e-Mousa village from Ardabil
Province, north-west of Iran, complained with abdominal
pain, nausea, and intestinal obstruction symptoms referred
to Ardabil Fatemi hospital. In laparotomy multiple intestinal
masses with peritoneal seeding resembling of a
malignant lesion were seen. After appendectomy and peritoneal
mass biopsy with numerous intraperitoneal adenopathy,
paraffin embedded blocks were prepared from
each tissues. A blood sample was taken from the patient
5 months later for serological diagnosis. Histopathological
examination of sections showed fibrofatty stroma with
dense mixed inflammatory cells infiltration and fibrosis in
peritoneal masses. Large numbers of ova of Fasciola spp.
were noted with typical circumscribed granulomas. Despite
of anti-fasciola treatment, IHA test for detecting anti F.
hepatica antibodies was positive 5 months after surgery
with a titer of 1/128. Due to multiple clinical manifestation
of extra-hepatic fascioliasis, its differential diagnosis from
intraperitoneal tumors or other similar diseases should be
considered
Indole pulse signalling regulates the cytoplasmic pH of E. coli in a memory-like manner
This is the final version. Available from the publisher via the DOI in this record.The data that support the findings of this study are available in Apollo (University of Cambridge Repository) at https://doi.org/10.17863/CAM.26410.Bacterial cells are critically dependent upon pH regulation. Here we demonstrate that indole plays a
critical role in the regulation of the cytoplasmic pH of Escherichia coli. Indole is an aromatic molecule
with diverse signalling roles. Two modes of indole signalling have been described: persistent and
pulse signalling. The latter is illustrated by the brief but intense elevation of intracellular indole during
stationary phase entry. We show that under conditions permitting indole production, cells maintain
their cytoplasmic pH at 7.2. In contrast, under conditions where no indole is produced, the cytoplasmic
pH is near 7.8. We demonstrate that pH regulation results from pulse, rather than persistent, indole
signalling. Furthermore, we illustrate that the relevant property of indole in this context is its ability to
conduct protons across the cytoplasmic membrane. Additionally, we show that the efect of the indole
pulse that occurs normally during stationary phase entry in rich medium remains as a “memory” to
maintain the cytoplasmic pH until entry into the next stationary phase. The indole-mediated reduction
in cytoplasmic pH may explain why indole provides E. coli with a degree of protection against stresses,
including some bactericidal antibiotics.Leverhulme TrustEngineering and Physical Sciences Research Council (EPSRC)Biotechnology and Biological Sciences Research Council (BBSRC)Winton Programme for the Physics of SustainabilityTrinity-Henry Barlow ScholarshipNational Physical Laboratory (UK)European Research Council (ERC
Dual E627K and D701N mutations in the PB2 protein of A(H7N9) influenza virus increased its virulence in mammalian models
The ongoing avian H7N9 influenza outbreaks in China have caused significant human fatal cases and the virus is becoming established in poultry. Mutations with potential to increase mammalian adaptation have occurred in the polymerase basic protein 2 (PB2) and other viral genes. Here we found that dual 627K and 701N mutations could readily occur during transmission of the virus among ferrets via direct physical contact, and these mutations conferred higher polymerase activity and improved viral replication in mammalian cells, and enhanced virulence in mice. Special attention needs to be paid to patients with such mutations, as these may serve as an indicator of higher virus replication and increased pathogenicity.published_or_final_versio
The role of electrons? spin in DNA oxidative damage recognition
Formation of 8-oxo-7,8-dihydro-20-deoxyguanosine (OG) is one of the most common forms of DNA oxidative damage found in human cells. Although this damage is prevalent in many disease states, it only marginally influences the structure and stability of double -stranded DNA (dsDNA). Therefore, it is a challenge to establish the mechanism by which this damage is detected by repair enzymes. We investigated the position-dependent effect of the damage on the interactions between dsDNA and oligopeptides using atomic force microscopy. The results were confirmed by monitoring the spin and location-dependent polarizability of the damaged DNA, applying a Hall device. The observations suggest that the interac-tion of peptide with DNA depends on oxidative damage in the DNA and on its location relative to the point of contact between the peptide and the DNA. Hence, a remote search mechanism for damage in DNA is possible
Acupuncture for chronic neck pain: a pilot for a randomised controlled trial
Background: Acupuncture is increasingly being used for many conditions including chronic neck pain. However the evidence remains inconclusive, indicating the need for further well-designed research. The aim of this study was to conduct a pilot randomised controlled parallel arm trial, to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain. Methods: Patients whose GPs had diagnosed neck pain were recruited from one general practice, and randomised to receive usual GP care only, or acupuncture ( up to 10 treatments over 3 months) as an adjunctive treatment to usual GP care. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ) at 3 months. The primary analysis was to determine the sample size for the full scale study. Results: Of the 227 patients with neck pain identified from the GP database, 28 (12.3%) consenting patients were eligible to participate in the pilot and 24 (10.5%) were recruited to the trial. Ten patients were randomised to acupuncture, receiving an average of eight treatments from one of four acupuncturists, and 14 were randomised to usual GP care alone. The sample size for the full scale trial was calculated from a clinically meaningful difference of 5% on the NPQ and, from this pilot, an adjusted standard deviation of 15.3%. Assuming 90% power at the 5% significance level, a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14%. In order to achieve this sample, one would need to identify patients from databases of GP practices with a total population of 230,000 patients, or approximately 15 GP practices roughly equal in size to the one involved in this study (i.e. 15,694 patients). Conclusion: This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for neck pain
Photoconductivity of biased graphene
Graphene is a promising candidate for optoelectronic applications such as
photodetectors, terahertz imagers, and plasmonic devices. The origin of
photoresponse in graphene junctions has been studied extensively and is
attributed to either thermoelectric or photovoltaic effects. In addition, hot
carrier transport and carrier multiplication are thought to play an important
role. Here we report the intrinsic photoresponse in biased but otherwise
homogeneous graphene. In this classic photoconductivity experiment, the
thermoelectric effects are insignificant. Instead, the photovoltaic and a
photo-induced bolometric effect dominate the photoresponse due to hot
photocarrier generation and subsequent lattice heating through electron-phonon
cooling channels respectively. The measured photocurrent displays polarity
reversal as it alternates between these two mechanisms in a backgate voltage
sweep. Our analysis yields elevated electron and phonon temperatures, with the
former an order higher than the latter, confirming that hot electrons drive the
photovoltaic response of homogeneous graphene near the Dirac point
A Self-Organizing Algorithm for Modeling Protein Loops
Protein loops, the flexible short segments connecting two stable secondary
structural units in proteins, play a critical role in protein structure and
function. Constructing chemically sensible conformations of protein loops that
seamlessly bridge the gap between the anchor points without introducing any
steric collisions remains an open challenge. A variety of algorithms have been
developed to tackle the loop closure problem, ranging from inverse kinematics to
knowledge-based approaches that utilize pre-existing fragments extracted from
known protein structures. However, many of these approaches focus on the
generation of conformations that mainly satisfy the fixed end point condition,
leaving the steric constraints to be resolved in subsequent post-processing
steps. In the present work, we describe a simple solution that simultaneously
satisfies not only the end point and steric conditions, but also chirality and
planarity constraints. Starting from random initial atomic coordinates, each
individual conformation is generated independently by using a simple alternating
scheme of pairwise distance adjustments of randomly chosen atoms, followed by
fast geometric matching of the conformationally rigid components of the
constituent amino acids. The method is conceptually simple, numerically stable
and computationally efficient. Very importantly, additional constraints, such as
those derived from NMR experiments, hydrogen bonds or salt bridges, can be
incorporated into the algorithm in a straightforward and inexpensive way, making
the method ideal for solving more complex multi-loop problems. The remarkable
performance and robustness of the algorithm are demonstrated on a set of protein
loops of length 4, 8, and 12 that have been used in previous studies
Detecting single viruses and nanoparticles using whispering gallery microlasers
Detection and characterization of individual nano-scale particles, virions,
and pathogens are of paramount importance to human health, homeland security,
diagnostic and environmental monitoring[1]. There is a strong demand for
high-resolution, portable, and cost-effective systems to make label-free
detection and measurement of individual nanoparticles, molecules, and viruses
[2-6]. Here, we report an easily accessible, real-time and label-free detection
method with single nanoparticle resolution that surpasses detection limit of
existing micro- and nano-photonic devices. This is achieved by using an
ultra-narrow linewidth whispering gallery microlaser, whose lasing line
undergoes frequency splitting upon the binding of individual nano-objects. We
demonstrate detection of polystyrene and gold nanoparticles as small as 15 nm
and 10 nm in radius, respectively, and Influenza A virions by monitoring
changes in self-heterodyning beat note of the split lasing modes. Experiments
are performed in both air and aqueous environment. The built-in self-heterodyne
interferometric method achieved in a microlaser provides a self-reference
scheme with extraordinary sensitivity [7,8], and paves the way for detection
and spectroscopy of nano-scale objects using micro- and nano-lasers.Comment: Main Text: 14 pages, 5 figures, 27 references. Supplement: 26 pages,
12 figures, 26 reference
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