1,835 research outputs found
Значение экспрессии рАКТ1 при диффузной В-крупноклеточной лимфоме
Aim. To evaluate the prognostic value of pAKT1 expression by tumor cells in patients with diffuse large B-cell lymphoma.Materials and methods. The study included 90 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), who were treated at the clinic of Kirov Research Institute of Hematology and Blood Transfusion from 2014 to 2017 and received standard first-line polychemotherapy according to the R-CHOP regimen. Using immunohistochemical and morphometric methods, the relative number of tumor cells expressing pAKT1 was determined. Using the two-sided Fisher’s exact test, the relationship of different levels of marker expression with clinical and laboratory parameters of patients and long-term treatment results was analyzed. The impact of pAKT1 on the risk of an adverse event was assessed using the Cox regression analysis.Results. Overexpression of pAKT1 is associated with unfavorable clinical characteristics of patients with DLBCL, excessive expression of the BCL2 and c-Myc oncoproteins, as well as with low rates of overall and progressive survival. Overexpression of pAKT1 is an independent prognostic factor and statistically significantly affects the risk of an adverse outcome in DLBCL.Conclusion. The degree of pAKT1 expression is an informative criterion that allows to predict the course of diffuse large B-cell lymphoma. It is advisable to use the indicated marker when stratifying patients into risk groups.Цель – оценить прогностическое значение экспрессии рАКТ1 опухолевыми клетками у больных диффузной В-крупноклеточной лимфомой.Материалы и методы. В исследование включены 90 пациентов с впервые диагностированной диффузной В-крупноклеточной лимфомой (ДВККЛ), наблюдавшиеся в клинике института с 2014 по 2017 г. и получавшие стандартную полихимиотерапию первой линии по схеме R-CHOP. С помощью иммуногистохимического и морфометрического методов определено относительное количество экспрессирующих рАКТ1 опухолевых клеток. С помощью точного двухстороннего критерия Фишера проанализирована взаимосвязь различных уровней экспрессии маркера с клинико-лабораторными показателями пациентов и отдаленными результатами лечения. Оценку влияния рАКТ1 на риск наступления неблагоприятного события проводили с помощью регрессионного анализа Кокса.Результаты. Гиперэкспрессия рАКТ1 ассоциирована с неблагоприятными клиническими характеристиками больных диффузной В-крупноклеточной лимфомой, избыточной экспрессией онкобелков BCL2, cMyc, а также низкими показателями общей и беспрогрессивной выживаемости. Гиперэкспрессия рАКТ1 является независимым фактором прогноза и статистически значимо влияет на риск возникновения неблагоприятного исхода при ДВККЛ.Заключение. Степень экспрессии рАКТ1 является информативным критерием, позволяющим прогнозировать течение диффузной В-крупноклеточной лимфомы. Указанный маркер целесообразно использовать при стратификации пациентов на группы риска
Key Modulatory Role of Presynaptic Adenosine A 2A
Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1 and D2 receptors, respectively. Adenosine A2A receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2A receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2A receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders
Detailing patient specific modelling to aid clinical decision-making
The anatomy of the craniofacial skeleton has been described through the aid of dissection identifying hard and soft tissue structures. Although the macro and microscopic investigation of internal facial tissues have provided invaluable information on constitution of the tissues it is important to inspect and model facial tissues in the living individual. Detailing the form and function of facial tissues will be invaluable in clinical diagnoses and planned corrective surgical interventions such as management of facial palsies and craniofacial disharmony/anomalies.
Recent advances in lower-cost, non-invasive imaging and computing power (surface scanning, Cone Beam Computerized Tomography (CBCT) and Magnetic Resonance (MRI)) has enabled the ability to capture and process surface and internal structures to a high resolution. The three-dimensional surface facial capture has enabled characterization of facial features all of which will influence subtleties in facial movement and surgical planning.
This chapter will describe the factors that influence facial morphology in terms of gender and age differences, facial movement—surface and underlying structures, modeling based on average structures, orientation of facial muscle fibers, biomechanics of movement—proof of principle and surgical intervention
An NLO QCD analysis of inclusive cross-section and jet-production data from the ZEUS experiment
The ZEUS inclusive differential cross-section data from HERA, for charged and
neutral current processes taken with e+ and e- beams, together with
differential cross-section data on inclusive jet production in e+ p scattering
and dijet production in \gamma p scattering, have been used in a new NLO QCD
analysis to extract the parton distribution functions of the proton. The input
of jet data constrains the gluon and allows an accurate extraction of
\alpha_s(M_Z) at NLO;
\alpha_s(M_Z) = 0.1183 \pm 0.0028(exp.) \pm 0.0008(model)
An additional uncertainty from the choice of scales is estimated as \pm
0.005. This is the first extraction of \alpha_s(M_Z) from HERA data alone.Comment: 37 pages, 14 figures, to be submitted to EPJC. PDFs available at
http://durpdg.dur.ac.uk/hepdata in LHAPDFv
High-E_T dijet photoproduction at HERA
The cross section for high-E_T dijet production in photoproduction has been
measured with the ZEUS detector at HERA using an integrated luminosity of 81.8
pb-1. The events were required to have a virtuality of the incoming photon,
Q^2, of less than 1 GeV^2 and a photon-proton centre-of-mass energy in the
range 142 < W < 293 GeV. Events were selected if at least two jets satisfied
the transverse-energy requirements of E_T(jet1) > 20 GeV and E_T(jet2) > 15 GeV
and pseudorapidity requirements of -1 < eta(jet1,2) < 3, with at least one of
the jets satisfying -1 < eta(jet) < 2.5. The measurements show sensitivity to
the parton distributions in the photon and proton and effects beyond
next-to-leading order in QCD. Hence these data can be used to constrain further
the parton densities in the proton and photon.Comment: 36 pages, 13 figures, 20 tables, including minor revisions from
referees. Accepted by Phys. Rev.
Expression and Differential Responsiveness of Central Nervous System Glial Cell Populations to the Acute Phase Protein Serum Amyloid A
Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-\u3b1 and lipopolysaccaride (LPS). TNF-\u3b1 time-dependently increased Saa1 (but not Saa3) mRNA expression in purified microglia, enriched astrocytes, and OPCs (as did LPS for microglia and astrocytes). Astrocytes depleted of microglia were markedly less responsive to TNF-\u3b1 and LPS, even after re-addition of microglia. Microglia and enriched astrocytes showed complementary Saa1 expression profiles following TNF-\u3b1 or LPS challenge, being higher in microglia with TNF-\u3b1 and higher in astrocytes with LPS. Recombinant human apo-SAA stimulated production of both inflammatory mediators and its own mRNA in microglia and enriched, but not microglia-depleted astrocytes. Co-ultramicronized palmitoylethanolamide/luteolin, an established anti-inflammatory/neuroprotective agent, reduced Saa1 expression in OPCs subjected to TNF-\u3b1 treatment. These last data, together with past findings suggest that co-ultramicronized palmitoylethanolamide/luteolin may be a novel approach in the treatment of inflammatory demyelinating disorders like MS
Dissociation of virtual photons in events with a leading proton at HERA
The ZEUS detector has been used to study dissociation of virtual photons in
events with a leading proton, gamma^* p -> X p, in e^+p collisions at HERA. The
data cover photon virtualities in two ranges, 0.03<Q^2<0.60 GeV^2 and 2<Q^2<100
GeV^2, with M_X>1.5 GeV, where M_X is the mass of the hadronic final state, X.
Events were required to have a leading proton, detected in the ZEUS leading
proton spectrometer, carrying at least 90% of the incoming proton energy. The
cross section is presented as a function of t, the squared four-momentum
transfer at the proton vertex, Phi, the azimuthal angle between the positron
scattering plane and the proton scattering plane, and Q^2. The data are
presented in terms of the diffractive structure function, F_2^D(3). A
next-to-leading-order QCD fit to the higher-Q^2 data set and to previously
published diffractive charm production data is presented
Inclusive jet cross sections and dijet correlations in photoproduction at HERA
Inclusive jet cross sections in photoproduction for events containing a
meson have been measured with the ZEUS detector at HERA using an integrated
luminosity of . The events were required to have a
virtuality of the incoming photon, , of less than 1 GeV, and a
photon-proton centre-of-mass energy in the range . The measurements are compared with next-to-leading-order (NLO) QCD
calculations. Good agreement is found with the NLO calculations over most of
the measured kinematic region. Requiring a second jet in the event allowed a
more detailed comparison with QCD calculations. The measured dijet cross
sections are also compared to Monte Carlo (MC) models which incorporate
leading-order matrix elements followed by parton showers and hadronisation. The
NLO QCD predictions are in general agreement with the data although differences
have been isolated to regions where contributions from higher orders are
expected to be significant. The MC models give a better description than the
NLO predictions of the shape of the measured cross sections.Comment: 43 pages, 12 figures, charm jets ZEU
De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development
Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD
Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata
C1 - Journal Articles RefereedAIMS: Increased sympathetic tone in obstructive sleep apnoea results from recurrent episodes of systemic hypoxia and hypercapnia and might be an important contributor to the development of cardiovascular disease. In this study, we re-evaluated the role of a specific population of sympathoexcitatory catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata in the control of sympathetic vasomotor tone, arterial blood pressure, and hypercapnia-evoked sympathetic and cardiovascular responses. METHODS AND RESULTS: In anaesthetized rats in vivo and perfused rat working heart brainstem preparations in situ, C1 neurones were acutely silenced by application of the insect peptide allatostatin following cell-specific targeting with a lentiviral vector to express the inhibitory Drosophila allatostatin receptor. In anaesthetized rats with denervated peripheral chemoreceptors, acute inhibition of 50% of the C1 neuronal population resulted in ∼50% reduction in renal sympathetic nerve activity and a profound fall in arterial blood pressure (by ∼25 mmHg). However, under these conditions systemic hypercapnia still evoked vigorous sympathetic activation and the slopes of the CO(2)-evoked sympathoexcitatory and cardiovascular responses were not affected by inhibition of C1 neurones. Inhibition of C1 neurones in situ resulted in a reversible fall in perfusion pressure and the amplitude of respiratory-related bursts of thoracic sympathetic nerve activity. CONCLUSION: These data confirm a fundamental physiological role of medullary catecholaminergic C1 neurones in maintaining resting sympathetic vasomotor tone and arterial blood pressure. However, C1 neurones do not appear to mediate sympathoexcitation evoked by central actions of CO(2)
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