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1.
Nature ; 582(7811): 294-297, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32523118

RESUMEN

The primary structural component of the bacterial cell wall is peptidoglycan, which is essential for viability and the synthesis of which is the target for crucial antibiotics1,2. Peptidoglycan is a single macromolecule made of glycan chains crosslinked by peptide side branches that surrounds the cell, acting as a constraint to internal turgor1,3. In Gram-positive bacteria, peptidoglycan is tens of nanometres thick, generally portrayed as a homogeneous structure that provides mechanical strength4-6. Here we applied atomic force microscopy7-12 to interrogate the morphologically distinct Staphylococcus aureus and Bacillus subtilis species, using live cells and purified peptidoglycan. The mature surface of live cells is characterized by a landscape of large (up to 60 nm in diameter), deep (up to 23 nm) pores constituting a disordered gel of peptidoglycan. The inner peptidoglycan surface, consisting of more nascent material, is much denser, with glycan strand spacing typically less than 7 nm. The inner surface architecture is location dependent; the cylinder of B. subtilis has dense circumferential orientation, while in S. aureus and division septa for both species, peptidoglycan is dense but randomly oriented. Revealing the molecular architecture of the cell envelope frames our understanding of its mechanical properties and role as the environmental interface13,14, providing information complementary to traditional structural biology approaches.


Asunto(s)
Bacillus subtilis/citología , Bacillus subtilis/ultraestructura , Pared Celular/química , Pared Celular/ultraestructura , Microscopía de Fuerza Atómica , Staphylococcus aureus/citología , Staphylococcus aureus/ultraestructura , Bacillus subtilis/química , Viabilidad Microbiana , Peptidoglicano/química , Peptidoglicano/aislamiento & purificación , Peptidoglicano/ultraestructura , Staphylococcus aureus/química
2.
Mol Psychiatry ; 23(6): 1402-1409, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-28584286

RESUMEN

We conducted a genome-wide meta-analysis of cognitive empathy using the 'Reading the Mind in the Eyes' Test (Eyes Test) in 88,056 research volunteers of European Ancestry (44,574 females and 43,482 males) from 23andMe Inc., and an additional 1497 research volunteers of European Ancestry (891 females and 606 males) from the Brisbane Longitudinal Twin Study. We confirmed a female advantage on the Eyes Test (Cohen's d=0.21, P<2.2 × 10-16), and identified a locus in 3p26.1 that is associated with scores on the Eyes Test in females (rs7641347, Pmeta=1.58 × 10-8). Common single nucleotide polymorphisms explained 5.8% (95% CI: 4.5%-7.2%; P=1.00 × 10-17) of the total trait variance in both sexes, and we identified a twin heritability of 28% (95% CI: 13%-42%). Finally, we identified significant genetic correlation between the Eyes Test and anorexia nervosa, openness (NEO-Five Factor Inventory), and different measures of educational attainment and cognitive aptitude.


Asunto(s)
Empatía/genética , Empatía/fisiología , Adulto , Anciano , Anorexia Nerviosa/genética , Cognición/fisiología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Trastornos Mentales/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores Sexuales , Gemelos , Población Blanca/genética
3.
Environ Monit Assess ; 191(4): 223, 2019 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-30879142

RESUMEN

Phosphorus (P) demand is likely to increase especially in legumes to harness greater benefits of nitrogen fixation under elevated CO2 condition. In the following study, seed yield and seed P uptake in cowpea increased by 26.8% and 20.9%, respectively, under elevated CO2 level. With an increase in phosphorus dose up to 12 mg kg-1, seed yield enhanced from 2.6 to 5.4 g plant-1. P application and cyanobacterial inoculation increased the microbial activity of soil, leading to increased availability of P. Under elevated CO2 condition, microbial activity, measured as dehydrogenase, acid phosphatase, and alkaline phosphatase activities showed stimulation. Soil available P also increased under elevated CO2 condition and was stimulated by both P application and cyanobacterial inoculation. Higher P uptake in elevated CO2 condition led to lower values of inorganic P in soil. Stepwise regression analysis showed that aboveground P uptake, soil available P, and alkaline phosphatase activity of soil influenced the yield while available P, and organic and inorganic P influenced the aboveground P uptake of the crop. This study revealed that under elevated CO2 condition, P application and cyanobacterial inoculation facilitated P uptake and yield, mediated through enhanced availability of nutrients, in cowpea crop.


Asunto(s)
Dióxido de Carbono/metabolismo , Cianobacterias/metabolismo , Fósforo/metabolismo , Vigna/metabolismo , Carbono , Dióxido de Carbono/análisis , Monitoreo del Ambiente , Nitrógeno , Fijación del Nitrógeno , Análisis de Regresión , Suelo/química , Vigna/crecimiento & desarrollo
4.
Mol Psychiatry ; 20(3): 369-76, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24888361

RESUMEN

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.


Asunto(s)
Síndrome de Asperger/sangre , Trastorno Autístico/sangre , Feto/metabolismo , Esteroides/metabolismo , Análisis de Varianza , Estudios de Casos y Controles , Cromatografía Liquida , Estudios de Cohortes , Dinamarca , Femenino , Edad Gestacional , Humanos , Hidrocortisona/metabolismo , Masculino , Análisis de Componente Principal , Espectrometría de Masas en Tándem
5.
NPJ Prim Care Respir Med ; 33(1): 6, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36750578

RESUMEN

Greater Manchester has a greater prevalence and worse asthma outcomes than the national average. This study aims to evaluate a digital approach to primary care asthma management and in particular the initial impact of implementing Clinical Decision Support System software in the form of a computer-guided consultation (CGC) in the setting of primary care asthma reviews in deprived areas of Greater Manchester. The CGC (LungHealth Ltd) is an intelligent decision support system ensuring accurate guideline-based staging of asthma and assessment of asthma control with the software subsequently prompting guideline-standard management. Patients on asthma registers in Greater Manchester Primary Care Networks were identified and underwent remote review by nursing staff using the CGC linked directly to the GP clinical system. Three-hundred thirty-eight patients (mean age 59 (SD 17) years; 60% Female) were reviewed. The CGC reported the patient's asthma control to be "Good" in 22%, "Partial" in 6% and "Poor" in 72%. ACT scores were significantly higher in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. The number of steroid courses and hospital admissions in the previous 12 months was significantly lower in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. Nineteen percent were found not to have a personalised asthma management plan during CGC review, which was alerted by the CGC and subsequently, all but 3 patients had this created on review completion (McNemar's test; p < 0.001). 5% were found not to have been prescribed regular inhaled steroid therapy resulting in the operator being alerted by the CGC in all cases. Overall, 44% underwent alteration in asthma therapy following the CGC review with 82% of these representing treatment escalation. An end-to-end digital service solution is feasible for Asthma within primary care and the utilisation of a CGC when conducting primary care asthma reviews increases implementation of guideline-level management thus addressing healthcare inequality while enabling identification of "high risk" asthma patients and guiding appropriate therapy escalation and de-escalation.


Asunto(s)
Asma , Disparidades en el Estado de Salud , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios de Factibilidad , Asma/tratamiento farmacológico , Derivación y Consulta , Computadores
6.
Neuroimage ; 59(2): 1571-81, 2012 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-21906686

RESUMEN

Research on the cortical sources of nociceptive laser-evoked brain potentials (LEPs) began almost two decades ago (Tarkka and Treede, 1993). Whereas there is a large consensus on the sources of the late part of the LEP waveform (N2 and P2 waves), the relative contribution of the primary somatosensory cortex (S1) to the early part of the LEP waveform (N1 wave) is still debated. To address this issue we recorded LEPs elicited by the stimulation of four limbs in a large population (n=35). Early LEP generators were estimated both at single-subject and group level, using three different approaches: distributed source analysis, dipolar source modeling, and probabilistic independent component analysis (ICA). We show that the scalp distribution of the earliest LEP response to hand stimulation was maximal over the central-parietal electrodes contralateral to the stimulated side, while that of the earliest LEP response to foot stimulation was maximal over the central-parietal midline electrodes. Crucially, all three approaches indicated hand and foot S1 areas as generators of the earliest LEP response. Altogether, these findings indicate that the earliest part of the scalp response elicited by a selective nociceptive stimulus is largely explained by activity in the contralateral S1, with negligible contribution from the secondary somatosensory cortex (S2).


Asunto(s)
Electroencefalografía/métodos , Potenciales Evocados Somatosensoriales , Dolor Nociceptivo/fisiopatología , Corteza Somatosensorial/fisiopatología , Adulto , Femenino , Humanos , Masculino
7.
J Virol ; 85(16): 8217-26, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21653673

RESUMEN

On the prereceptor-engaged HIV-1 envelope glycoprotein (Env) spike, epitope access by the membrane-proximal external region (MPER)-directed broadly neutralizing antibodies 2F5 and 4E10 remains unresolved. Data on binding to cell surface Env and entry data using primary isolates suggest inaccessibility of the 2F5 and 4E10 epitopes on the viral spike prior to receptor engagement, but trimer gel shift analysis and slow kinetics of shedding induced by 2F5 and 4E10 indicate otherwise. Therefore, it remains unclear if the epitopes themselves are formed in their antibody-bound state (or at least sampled) prior to receptor/coreceptor engagement or if receptor interactions both expose and form the MPER epitopes, presumably in the putative prefusion transitional intermediate. Here, we performed antibody-virus "washout experiments" using both lab-adapted and a panel of clade B primary isolates to analyze MPER accessibility. The neutralization activity of 2F5 and 4E10 against lab-adapted viruses and sensitive and moderately resistant viruses was largely unaffected by relatively rapid antibody-virus washing, suggesting direct interaction with the "static" spike. However, for more neutralization-resistant viruses, the 2F5 and 4E10 antibodies could neutralize only under the "no antibody-virus wash" conditions, implying that the MPER epitopes were not accessible prior to receptor engagement. Accessibility in the washout conditions could be precisely predicted by the relative resistance to neutralization in a standard neutralization format. These data are consistent with a model in which the local MPER antibody epitope conformations may be sampled on the native spike but are occluded to antibody by local steric or distal quaternary constraints adopted by highly resistant HIV-1 isolates.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Anti-VIH/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , Proteínas gp160 de Envoltorio del VIH/inmunología , Proteína gp41 de Envoltorio del VIH/inmunología , VIH-1/inmunología , Anticuerpos Monoclonales/metabolismo , Anticuerpos Neutralizantes/metabolismo , Afinidad de Anticuerpos , Sitios de Unión de Anticuerpos , Citometría de Flujo , Células HEK293 , Anticuerpos Anti-VIH/metabolismo , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteínas gp160 de Envoltorio del VIH/metabolismo , Proteína gp41 de Envoltorio del VIH/metabolismo , Células HeLa , Humanos , Pruebas de Neutralización , Estructura Cuaternaria de Proteína
8.
Mol Autism ; 12(1): 74, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34911565

RESUMEN

BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Adolescente , Biomarcadores , Estudios de Casos y Controles , Niño , Humanos , Índice de Severidad de la Enfermedad , Adulto Joven
9.
Phys Biol ; 7(2): 026003, 2010 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-20453297

RESUMEN

Chemotaxis is typically modeled in the context of cellular motion toward a static, exogenous source of chemoattractant. Here we propose a time-dependent mechanism of chemotaxis in which a self-propelled particle (e.g. a cell) releases a chemical that diffuses to fixed particles (targets) and signals the production of a second chemical by these targets. The particle then moves up concentration gradients of this second chemical, analogous to diffusive echolocation. When one target is present, we describe probe release strategies that optimize travel of the cell to the target. In the presence of multiple targets, the one selected by the cell depends on the strength and, interestingly, on the frequency of probe chemical release. Although involving an additional chemical signaling step, our chemical 'pinging' hypothesis allows for greater flexibility in regulating target selection, as seen in a number of physical or biological realizations.


Asunto(s)
Factores Quimiotácticos/metabolismo , Quimiotaxis , Comunicación Celular , Modelos Biológicos
10.
Thorax ; 64(10): 857-62, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19454410

RESUMEN

RATIONALE: Hyperglycaemia predicts a poor outcome in Intensive Care Unit (ICU) patients. Whether this is true for respiratory failure necessitating non-invasive ventilation (NIV) is not known. OBJECTIVES: To determine whether hyperglycaemia within 24 h of admission independently predicts outcome of NIV during acute decompensated ventilatory failure complicating chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: Patients with COPD presenting with acute hypercapnic respiratory failure at University Hospital Aintree between June 2006 and September 2007 and receiving NIV within 24 h of admission were studied prospectively. Random blood glucose levels were measured before NIV administration. RESULTS: 88 patients (mean baseline pH 7.25, PaCO(2) 10.20 kPa, and PaO(2) 8.19 kPa) met the inclusion criteria, with NIV normalising arterial pH off therapy in 79 (90%). After multivariate logistic regression, the following predicted outcome: baseline respiratory rate (OR 0.91; 95% CI 0.84 to 0.99), random glucose > or = 7 mmol/l (OR 0.07; 95% CI 0.007 to 0.63) and admission APACHE II (Acute Physiology and Chronic Health Evaluation II) score (OR 0.75; 95% CI 0.62 to 0.90). The combination of baseline respiratory rate (RR) <30 breaths/min and random glucose <7 mmol/l increased prediction of NIV success to 97%, whilst use of all three factors was 100% predictive. CONCLUSIONS: In acute decompensated ventilatory failure complicating COPD, hyperglycaemia upon presentation was associated with a poor outcome. Baseline RR and hyperglycaemia are as good at predicting clinical outcomes as the APACHE II score. Combining these variables increases predictive accuracy, providing a simple method of early risk stratification.


Asunto(s)
Glucemia/metabolismo , Hiperglucemia/etiología , Respiración con Presión Positiva , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Aguda , Anciano , Análisis de los Gases de la Sangre , Cuidados Críticos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Hipercapnia/etiología , Masculino , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Insuficiencia Respiratoria/etiología , Resultado del Tratamiento
11.
Eur Respir J ; 33(1): 49-60, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18799505

RESUMEN

Paradoxical inward displacement of the costal margin during inspiration is observed in many chronic obstructive pulmonary disease patients at rest but its importance is unclear. The current authors studied 20 patients (forced expiratory volume in one second 32.6+/-11.7, functional residual capacity 186+/-32% predicted) and 10 healthy controls at rest and during symptom-limited incremental exercise. With optoelectronic plethysmography, the phase shift between pulmonary and abdominal ribcage volumes and the percentage of inspiratory time the ribcage compartments moved in opposite directions were quantified, using control data to define the normal range of movement. Eight patients showed lower ribcage inspiratory paradox at rest (P+), while 12 patients did not (P-). This was unrelated to resting lung function or exercise tolerance. Total end-expiratory chest wall volume (EEV(cw)) increased immediately when exercise began in P+ patients, but later in exercise in P- patients. This difference in EEV(cw) was mainly due to a greater increase of end-expiratory pulmonary ribcage volume in P+ patients. During exercise, dyspnoea increased similarly in the two groups, while leg effort increased more markedly in the patients without paradox. In conclusion, lower ribcage paradox at rest is reproducible and associated with early-onset hyperinflation of the chest wall and predominant dyspnoea at end-exercise. When paradox is absent, the sense of leg effort becomes a more important symptom limiting exercise.


Asunto(s)
Ejercicio Físico/fisiología , Movimiento/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Mecánica Respiratoria/fisiología , Descanso/fisiología , Pared Torácica/fisiopatología , Anciano , Estudios de Casos y Controles , Disnea/etiología , Disnea/fisiopatología , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Pletismografía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Reproducibilidad de los Resultados
12.
Curr Oncol ; 16(4): 71-3, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19672428

RESUMEN

Hemangiopericytoma is a malignant vascular tumour of soft tissue. Microscopically, the tumour shows tightly packed cellular areas surrounding thin-walled branching blood vessels. Traditionally these tumours are treated using wide surgical excision. Only a very few cases of hemangiopericytoma of the prostate have been described worldwide. The feasibility of managing such a case with a combination of conservative surgery and adjuvant anti-malignancy treatment is unexplored. Here, we report a case of hemangiopericytoma of the prostate treated with local excision, with preservation of prostate, followed by adjuvant radiotherapy (40 Gy in 20 fractions to pelvis followed by 24 Gy in 12 fractions as boost to prostate) and chemotherapy (doxorubicin and iphosphamide). Post-treatment computed tomography scan after 4 weeks showed regression of pelvic lymph nodes and a normal-appearing prostate. Levels of serum prostate-specific and carcinogenic embryonic antigen were normal throughout the period of treatment. To date, followup has been uneventful, except for occasional bouts of diarrhea.We conclude that conservative surgery followed by adjuvant radiation and chemotherapy, with subsequent close follow-up, may adequately control localized disease in selected cases of hemangiopericytoma of the prostate. The role of conservative surgery in tumours located at other sites has yet to be defined.

13.
Sci Rep ; 9(1): 17873, 2019 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-31784539

RESUMEN

Fermionization is what happens to the state of strongly interacting repulsive bosons interacting with contact interactions in one spatial dimension. Crystallization is what happens for sufficiently strongly interacting repulsive bosons with dipolar interactions in one spatial dimension. Crystallization and fermionization resemble each other: in both cases - due to their repulsion - the bosons try to minimize their spatial overlap. We trace these two hallmark phases of strongly correlated one-dimensional bosonic systems by exploring their ground state properties using the one- and two-body density matrix. We solve the N-body Schrödinger equation accurately and from first principles using the multiconfigurational time-dependent Hartree for bosons (MCTDHB) and for fermions (MCTDHF) methods. Using the one- and two-body density, fermionization can be distinguished from crystallization in position space. For N interacting bosons, a splitting into an N-fold pattern in the one-body and two-body density is a unique feature of both, fermionization and crystallization. We demonstrate that this splitting is incomplete for fermionized bosons and restricted by the confinement potential. This incomplete splitting is a consequence of the convergence of the energy in the limit of infinite repulsion and is in agreement with complementary results that we obtain for fermions using MCTDHF. For crystalline bosons, in contrast, the splitting is complete: the interaction energy is capable of overcoming the confinement potential. Our results suggest that the spreading of the density as a function of the dipolar interaction strength diverges as a power law. We describe how to distinguish fermionization from crystallization experimentally from measurements of the one- and two-body density.

14.
J Biomol Struct Dyn ; 25(5): 543-51, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18282009

RESUMEN

The metabolism of Thiobacillus ferrooxidans involves electron transfer from the Fe+2 ions in the extracellular environment to the terminal oxygen in the bacterial cytoplasm through a series of periplasmic proteins like Rusticyanin (RCy), Cytochrome (Cyt c4), and Cytochrome oxidase (CcO). The energy minimization and MD studies reveal the stabilization of the three redox proteins in their ternary complex through the direct and water mediated H-bonds and electrostatic interaction. The surface exposed polar residues of the three proteins, i.e., RCy (His 143, Thr 146, Lys 81, Glu 20), Cyt c4 (Asp 5, 15, 52, Ser 14, Glu 61), and CcO (Asp 135, Glu 126, 140, 142, Thr 177) formed the intermolecular hydrogen bonds and stabilized the ternary complex. The oxygen (Oepsilon1) of Glu 126, 140, and 142 on subunit II of the CcO interact to the exposed side-chain and Ob atoms of the Asp 52 of Cyt c4 and Glu 20 and Leu 12 of RCy. The Asp 135 of subunit II also forms H-bond with the Nepsilon atom of Lys 81 of RCy. The Oepsilon1 of Glu 61 of Cyt c4 is also H-bonded to Ogamma atom of Thr 177 of CcO. Solvation followed by MD studies of the ternary protein complex revealed the presence of seven water molecules in the interfacial region of the interacting proteins. Three of the seven water molecules (W 79, W 437, and W 606) bridged the three proteins by forming the hydrogen bonded network (with the distances approximately 2.10-2.95 A) between the Lys 81 (RCy), Glu 61 (Cyt c4), and Asp 135 (CcO). Another water molecule W 603 was H-bonded to Tyr 122 (CcO) and interconnected the Lys 81 (RCy) and Asp 135 (CcO) through the water molecules W 606 and W 437. The other two water molecules (W 21 and W 455) bridged the RCy to Cyt c4 through H-bonds, whereas the remaining W 76 interconnected the His 53 (Cytc4) to Glu 126 (CcO) with distances approximately 2.95-3.0 A.


Asunto(s)
Azurina/química , Proteínas Bacterianas/química , Grupo Citocromo c/química , Complejo IV de Transporte de Electrones/química , Complejos Multiproteicos/química , Estructura Terciaria de Proteína , Transporte de Electrón , Enlace de Hidrógeno , Modelos Moleculares , Oxidación-Reducción , Thiobacillus/química
15.
Nat Commun ; 9(1): 2331, 2018 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-29899421

RESUMEN

The progress in the field of neural computation hinges on the use of hardware more efficient than the conventional microprocessors. Recent works have shown that mixed-signal integrated memristive circuits, especially their passive (0T1R) variety, may increase the neuromorphic network performance dramatically, leaving far behind their digital counterparts. The major obstacle, however, is immature memristor technology so that only limited functionality has been reported. Here we demonstrate operation of one-hidden layer perceptron classifier entirely in the mixed-signal integrated hardware, comprised of two passive 20 × 20 metal-oxide memristive crossbar arrays, board-integrated with discrete conventional components. The demonstrated network, whose hardware complexity is almost 10× higher as compared to previously reported functional classifier circuits based on passive memristive crossbars, achieves classification fidelity within 3% of that obtained in simulations, when using ex-situ training. The successful demonstration was facilitated by improvements in fabrication technology of memristors, specifically by lowering variations in their I-V characteristics.

17.
Sci Rep ; 7: 42429, 2017 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-28195239

RESUMEN

Silicon (Si) based complementary metal-oxide semiconductor (CMOS) technology has been the driving force of the information-technology revolution. However, scaling of CMOS technology as per Moore's law has reached a serious bottleneck. Among the emerging technologies memristive devices can be promising for both memory as well as computing applications. Hybrid CMOS/memristor circuits with CMOL (CMOS + "Molecular") architecture have been proposed to combine the extremely high density of the memristive devices with the robustness of CMOS technology, leading to terabit-scale memory and extremely efficient computing paradigm. In this work, we demonstrate a hybrid 3D CMOL circuit with 2 layers of memristive crossbars monolithically integrated on a pre-fabricated CMOS substrate. The integrated crossbars can be fully operated through the underlying CMOS circuitry. The memristive devices in both layers exhibit analog switching behavior with controlled tunability and stable multi-level operation. We perform dot-product operations with the 2D and 3D memristive crossbars to demonstrate the applicability of such 3D CMOL hybrid circuits as a multiply-add engine. To the best of our knowledge this is the first demonstration of a functional 3D CMOL hybrid circuit.

19.
Transl Psychiatry ; 7(4): e1090, 2017 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-28398337

RESUMEN

Autism spectrum conditions (ASC) are more prevalent in males than females. The biological basis of this difference remains unclear. It has been postulated that one of the primary causes of ASC is a partial disconnection of the frontal lobe from higher-order association areas during development (that is, a frontal 'disconnection syndrome'). Therefore, in the current study we investigated whether frontal connectivity differs between males and females with ASC. We recruited 98 adults with a confirmed high-functioning ASC diagnosis (61 males: aged 18-41 years; 37 females: aged 18-37 years) and 115 neurotypical controls (61 males: aged 18-45 years; 54 females: aged 18-52 years). Current ASC symptoms were evaluated using the Autism Diagnostic Observation Schedule (ADOS). Diffusion tensor imaging was performed and fractional anisotropy (FA) maps were created. Mean FA values were determined for five frontal fiber bundles and two non-frontal fiber tracts. Between-group differences in mean tract FA, as well as sex-by-diagnosis interactions were assessed. Additional analyses including ADOS scores informed us on the influence of current ASC symptom severity on frontal connectivity. We found that males with ASC had higher scores of current symptom severity than females, and had significantly lower mean FA values for all but one tract compared to controls. No differences were found between females with or without ASC. Significant sex-by-diagnosis effects were limited to the frontal tracts. Taking current ASC symptom severity scores into account did not alter the findings, although the observed power for these analyses varied. We suggest these findings of frontal connectivity abnormalities in males with ASC, but not in females with ASC, have the potential to inform us on some of the sex differences reported in the behavioral phenotype of ASC.


Asunto(s)
Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Imagen de Difusión Tensora , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/patología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Adulto Joven
20.
Postgrad Med J ; 82(969): 438-45, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16822920

RESUMEN

Acute ventilatory failure is a challenging yet increasingly common medical emergency reflecting the growing burden of respiratory disease. It is not a diagnosis in itself but the end result of a diversity of disease processes culminating in arterial hypoxaemia and hypercapnia. This review focuses on key management issues including giving appropriate oxygen therapy, treatment of the underlying aetiology as well as any precipitant factors and provision of assisted ventilation if required. Ventilatory assistance can be provided both invasively and non-invasively and the indications for either or both forms of assisted ventilation are discussed. Further emphasis is needed regarding advanced directives of care and clinicians should be aware of ethical issues regarding assisted ventilation.


Asunto(s)
Insuficiencia Respiratoria/terapia , Enfermedad Aguda , Humanos , Oxígeno/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Respiración Artificial/métodos , Insuficiencia Respiratoria/etiología
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