813 research outputs found
Evolution of strigolactone receptors by gradual neofunctionalization of KAI2 paralogues
Background: Strigolactones (SLs) are a class of plant hormones that control many aspects of plant growth. The SL signalling mechanism is homologous to that of karrikins (KARs), smoke-derived compounds that stimulate seed germination. In angiosperms, the SL receptor is an a/p hydrolase known as DWARF14 (D14); its close homologue, KARRIKIN INSENSITIVE2 (KAI2), functions as a KAR receptor, and likely recognizes an uncharacterized, endogenous signal (‘KL’). Previous phylogenetic analyses have suggested that the KAI2 lineage is ancestral in land plants, and that canonical D14-type SL receptors only arose in seed plants; this is paradoxical, however, as nonvascular plants synthesize and respond to SLs. Results: We have used a combination of phylogenetic and structural approaches to re-assess the evolution of the D14/KAI2 family in land plants. We analyzed 339 members of the D14/KAI2 family from land plants and charophyte algae. Our phylogenetic analyses show that the divergence between the eu-KAI2 lineage and the DDK (D14/DLK2/KAI2) lineage that includes D14 occurred very early in land plant evolution. We show that eu-KAI2 proteins are highly conserved, and have unique features not found in DDK proteins. Conversely, we show that DDK proteins show considerable sequence and structural variation to each other, and lack clearly definable characteristics. We use homology modelling to show that the earliest members of the DDK lineage structurally resemble KAI2, and that SL receptors in non-seed plants likely do not have D14-like structure. We also show that certain groups of DDK proteins lack the otherwise conserved MAX2-interface, and may thus function independently of MAX2, which we show is highly conserved throughout land plant evolution. Conclusions: Our results suggest D14-like structure is not required for SL perception, and that SL perception has relatively relaxed structural requirements compared to KAI2-mediated signalling. We suggest that SL perception gradually evolved by neo-functionalization within the DDK lineage, and that the transition from KAI2-like to D14-like protein may have been driven by interactions with protein partners, rather than being required for SL perception per se
Variation in cervical and breast cancer screening coverage in England: a cross-sectional analysis to characterise districts with atypical behaviour
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
This article was published in BMJ Open following peer review and can also be viewed on the journal’s website at http://bmjopen.bmj.com
Assessing the Consultation and Relational Empathy (CARE) Measure in sexual health nurses' consultations
Background:
Increasingly healthcare policies emphasise the importance of person-centred, empathic care. Consequently, healthcare professionals are expected to demonstrate the ‘human’ aspects of care in training and in practice. The Consultation and Relational Empathy (CARE) Measure is a patient-rated measure of the interpersonal skills of healthcare practitioners. It has been widely validated for use by healthcare professionals in both primary and secondary care. This paper reports on the validity and reliability of the CARE Measure with sexual health nurses.
Methods:
Patient questionnaires were collected for 943 consultations with 20 sexual health nurses. Participating patients self-completed the questionnaire immediately after the encounter with the nurse. The questionnaire included the ten item CARE Measure, the Patient Enablement Index, and overall satisfaction instruments. Construct validity was assessed through Spearman’s correlation and principal component analysis. Internal consistence was assessed through Cronbach’s alpha and the inter-rater reliability through Generalisability Theory. Data were collected in 2013 in Scotland.
Results:
Female patients completed 68% of the questionnaires. The mean patient age was 28.8 years (standard deviation 9.8 years). Two of the 20 participating nurses withdrew from the study. Most patients (71.7%) regarded the CARE Measure items as very important to their consultation and the number of ‘not applicable’ and missing responses’ were low (2.6% and 0.1% respectively). The participating nurses had high CARE Measure scores; out of a maximum possible score of 50, the overall mean CARE measure score was 47.8 (standard deviation 4.4). The scores were moderately correlated with patient enablement (rho = 0.232, p = 0.001) and overall satisfaction (rho = 0.377, p = 0.001. Cronbach’s alpha showed the measure’s high internal consistency (Cronbach’s alpha coefficient = 0.95), but the inter-rater reliability could not be calculated due to the high achieved CARE Measure scores that varied little between nurses.
Conclusions:
Within this clinical context the CARE Measure has high perceived relevance and face validity. The findings support construct validity and some evidence of reliability. The high CARE Measure scores may have been due to sample bias. A future study which ensures a representative sample of patients on a larger group of nurses is required to determine whether the measure can discriminate between nurses
Proteolytic maturation of α 2 δ represents a checkpoint for activation and neuronal trafficking of latent calcium channels
The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ. Uncleaved α2δ does not support trafficking of CaV2.2 channel complexes into neuronal processes, and inhibits Ca2+ entry into synaptic boutons, and we can reverse this by controlled intracellular proteolytic cleavage. We propose a model whereby uncleaved α2δ subunits maintain immature calcium channels in an inhibited state. Proteolytic processing of α2δ then permits voltage-dependent activation of the channels, acting as a checkpoint allowing trafficking only of mature calcium channel complexes into neuronal processes
A filament of dark matter between two clusters of galaxies
It is a firm prediction of the concordance Cold Dark Matter (CDM)
cosmological model that galaxy clusters live at the intersection of large-scale
structure filaments. The thread-like structure of this "cosmic web" has been
traced by galaxy redshift surveys for decades. More recently the Warm-Hot
Intergalactic Medium (WHIM) residing in low redshift filaments has been
observed in emission and absorption. However, a reliable direct detection of
the underlying Dark Matter skeleton, which should contain more than half of all
matter, remained elusive, as earlier candidates for such detections were either
falsified or suffered from low signal-to-noise ratios and unphysical
misalignements of dark and luminous matter. Here we report the detection of a
dark matter filament connecting the two main components of the Abell 222/223
supercluster system from its weak gravitational lensing signal, both in a
non-parametric mass reconstruction and in parametric model fits. This filament
is coincident with an overdensity of galaxies and diffuse, soft X-ray emission
and contributes mass comparable to that of an additional galaxy cluster to the
total mass of the supercluster. Combined with X-ray observations, we place an
upper limit of 0.09 on the hot gas fraction, the mass of X-ray emitting gas
divided by the total mass, in the filament.Comment: Nature, in pres
The Heartbleed bug : insecurity repackaged, rebranded and resold
The emergence of a post-industrial information economy shaped by and around networked communication technology has presented new opportunities for identity theft. In particular, the accidental leakage or deliberate harvesting of information, via either hacking or social engineering, is an omnipresent threat to a large number of commercial organisations and state agencies who manage digital databases and sociotechnical forms of data. Throughout the twenty-first century the global media have reported on a series of data breaches fuelling amongst the public an anxiety concerning the safety and security of their personal and financial data. With concern outpacing reliable information a reassurance gap has emerged between the public's expectations and the state's ability to provide safety and security online. This disparity presents a significant opportunity for a commercial computer crime control industry who has sought to position itself as being able to offer consumer citizens the antidotes for such ills. This paper considers how neoliberal discourses of cybercrime control are packaged, branded and sold, through an examination of the social construction of the Heartbleed bug. It demonstrates how security company Codenomicon masterfully communicated the vulnerability, the product of a simple coding error, through its name, a logo and an accompanying website, in turn, shaping news coverage across the mainstream media and beyond
Operator theory and function theory in Drury-Arveson space and its quotients
The Drury-Arveson space , also known as symmetric Fock space or the
-shift space, is a Hilbert function space that has a natural -tuple of
operators acting on it, which gives it the structure of a Hilbert module. This
survey aims to introduce the Drury-Arveson space, to give a panoramic view of
the main operator theoretic and function theoretic aspects of this space, and
to describe the universal role that it plays in multivariable operator theory
and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page
Is Our Universe Natural?
It goes without saying that we are stuck with the universe we have.
Nevertheless, we would like to go beyond simply describing our observed
universe, and try to understand why it is that way rather than some other way.
Physicists and cosmologists have been exploring increasingly ambitious ideas
that attempt to explain why certain features of our universe aren't as
surprising as they might first appear.Comment: Invited review for Nature, 11 page
Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis
Increased glucose uptake mediated by glucose
transporters and reliance on glycolysis are common features
of malignant cells. Hypoxia-inducible factor-1α supports the
adaptation of hypoxic cells by inducing genes related to
glucose metabolism. The contribution of glucose transporter
(GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to
tumor behavior and their prognostic value in head and neck
cancers remains unclear. The aim of this study was to examine
the predictive value of GLUT1, GLUT3, and HIF-1α messenger
RNA (mRNA)/protein expression as markers of tumor
aggressiveness and prognosis in laryngeal cancer. The level of
hypoxia/metabolic marker genes was determined in 106 squamous
cell laryngeal cancer (SCC) and 73 noncancerous
matched mucosa (NCM) controls using quantitative realtime
PCR. The related protein levels were analyzed by
Western blot. Positive expression of SLC2A1, SLC2A3, and
HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC
specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer
samples. Higher levels of mRNA/protein for GLUT1 and
HIF-1α were noted in SCC compared to NCM (p<0.05).
SLC2A1 was found to have a positive relationship with grade,
tumor front grading (TFG) score, and depth and mode of
invasion (p<0.05). SLC2A3 was related to grade and invasion
type (p<0.05). There were also relationships of HIF-1α with
pTNM, TFG scale, invasion depth and mode, tumor recurrences,
and overall survival (p<0.05). In addition, more advanced
tumors were found to be more likely to demonstrate
positive expression of these proteins. In conclusion, the
hypoxia/metabolic markers studied could be used as molecular
markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory
fund of the Department of Cytobiochemistry, University of Łódź, Poland
(506/811), and by grant fromtheNational Science Council, Poland (N403
043 32/2326)
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