Mechanistic aspects of thioflavin-T self-aggregation and DNA binding: evidence for dimer attack on DNA grooves

Thioflavin-T (TFT) is a fluorescent marker widely employed in biomedical research but the mechanism of its binding to polynucleotides has been poorly understood. This paper presents a study of the mechanisms of TFT self-aggregation and binding to DNA. Relaxation kinetics of TFT solutions show that the cyanine undergoes dimerization followed by dimer isomerisation. The interaction of TFT with DNA has been investigated using static methods, such as spectrophotometric and spectrofluorometric titrations under different conditions (salt content, temperature), fluorescence quenching, viscometric experiments and the T-jump relaxation method. The combined use of these techniques enabled us to show that the TFT monomer undergoes intercalation between the DNA base pairs and external binding according to a branched mechanism. Moreover, it has also been observed that, under dye excess conditions, the TFT dimer binds to the DNA grooves. The molecular structures of intercalated TFT and the groove-bound TFT dimer are obtained by performing QM/MM MD simulations

Oocyte retrieval difficulties in women with ovarian endometriomas

Research question: What are the frequency, characteristics and consequences of technical diffiiculties encountered by physicians when carrying out oocyte retrieval in women with ovarian endometriomas? Design: We prospectively recruited women undergoing IVF and compared technical difficulties between women with (n = 56) and without (n = 227) endometriomas. Results: In exposed women, the cyst had to be transfixed in eight cases (14%, 95% CI 7 to 25%) and accidental contamination of the follicular fluid with the endometrioma content was recorded in nine women (16%, 95% CI 8 to 27%). Moreover, follicular aspiration was more frequently incomplete (OR 3.6, 95% CI 1.4 to 9.6). In contrast, the retrievals were not deemed to be more technically difficult by the physicians and the rate of oocytes retrieved per developed follicle did not differ. No pelvic infections or cyst ruptures were recorded (0%, 95% CI 0 to 5%). Conclusions: Oocyte retrieval in women with ovarian endometriomas is more problematic but the magnitude of these increased difficulties is modest

Qalb ta’ Tifel

Ġabra ta’ poeżiji u proża li tinkludi: Lil Malta ta’ Dun Karm – Fuq il-Fruntiera ta’ Dun Karm – Jum li jibqa’ jissemma ta’ Ġużè Chetcuti – Xbihet Malta ta’ Arthur V. Vassallo – Għanja ta’ Mħabba ta’ Ġużè Chetcuti – Żewġ Poeżijiet tal-kittieb Malti Antonio Calleja ta’ A. C. – Twettiqa ta’ Calleja – Lil Ħabib Għeluq Sninu ta’ Calleja – Taħt is-Salib ta’ R. M. B. – Lil Dun Karm ta’ Fran. Camilleri – Frak mill-weraq ta’ Byron ta’ A. C. – Irrid Immur Ta’ Xbiex ta’ Fran. Camilleri – Il-Cottonera fil-Ħamrun ta’ N. Biancardi – Qalb ta’ Tifel ta’ R. M. B.N/

Air Raid

Ġabra ta’ poeżiji u proża li tinkludi: Dwejjaq Missirijietna ta’ Rużar Briffa – Xemx ta’ Settembru ta’ Vic. Apap – God Save the King ta’ Ġużè Galea – It-8 ta’ Settembru Londra, 1942 ta’ A. V. Vassallo – Wenzu jsib lil Luċija f’Lazzarett ta’ Dun Pawl – MDLXV ta’ Albert M. Cassola – Innu lil San Duminku ta’ Gużman – Innu lill-Bambina – Il-Għanja tar-Rebħa! ta’ N. Biancardi – Air Raid ta’ E. Agius.N/

Machine-learning Support to Individual Diagnosis of Mild Cognitive Impairment Using Multimodal MRI and Cognitive Assessments

Background: Understanding whether the cognitive profile of a patient indicates mild cognitive impairment (MCI) or performance levels within normality is often a clinical challenge. The use of resting-state functional magnetic resonance imaging (RS-fMRI) and machine learning may represent valid aids in clinical settings for the identification of MCI patients. Methods: Machine-learning models were computed to test the classificatory accuracy of cognitive, volumetric [structural magnetic resonance imaging (sMRI)] and blood oxygen level dependent-connectivity (extracted from RS-fMRI) features, in single-modality and mixed classifiers. Results: The best and most significant classifier was the RS-fMRI+Cognitive mixed classifier (94% accuracy), whereas the worst performing was the sMRI classifier (∼80%). The mixed global (sMRI+RS-fMRI+Cognitive) had a slightly lower accuracy (∼90%), although not statistically different from the mixed RS-fMRI+Cognitive classifier. The most important cognitive features were indices of declarative memory and semantic processing. The crucial volumetric feature was the hippocampus. The RS-fMRI features selected by the algorithms were heavily based on the connectivity of mediotemporal, left temporal, and other neocortical regions. Conclusion: Feature selection was profoundly driven by statistical independence. Some features showed no between-group differences, or showed a trend in either direction. This indicates that clinically relevant brain alterations typical of MCI might be subtle and not inferable from group analysis

Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and 3He-MRI at a lung volume of end-inspiratory tidal volume (EIVT). In addition, 28 patients performed 3He-MRI at total lung capacity. 3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection-diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIVT strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=-0.79 and r=-0.78, respectively). Two distinct 3He-MRI patterns were highlighted: patients with abnormal FEV1 had significantly (p<0.001) larger, but fewer, contiguous defects than those with normal FEV1, who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EIVT, VDP and VHI reduced in all subjects (p<0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities

Behavioral Indices of Neuropsychological Processing Implicated in Moral Domain Reasoning amongst Children and Adolescents

Moral domain theory posits that moral knowledge is organized in separate domains related to moral and socio-conventional rules, with the latter being reliant on a statement made by authority. Domains may be contingent on different neuropsychological processing that may vary with age. Behavioral indices were measured in three age groups, to detect differences in the neuropsychological processing allegedly involved in the evaluation of rule transgressions in different domains. Acceptance of the transgressions was also investigated. Twenty-four children, 32 early adolescents, and 31 adolescents judged acceptability of rule transgressions when an authority figure allowed the transgression. Across age, moral-rule transgressions were less accepted and took significantly longer to be evaluated. In evaluating moral rule scenarios, children had the longest reaction times. Older adolescents took the least amount of time evaluating socio-conventional rule scenarios. Results suggest differences in the neuropsychological processing underlying decision making for moral and socio-conventional domains and that rule comprehension and distinction amongst domains increase by age

Dendritic Peptide Release Mediates Interpopulation Crosstalk between Neurosecretory and Preautonomic Networks

SummaryAlthough communication between neurons is considered a function of the synapse, neurons also release neurotransmitter from their dendrites. We found that dendritic transmitter release coordinates activity across distinct neuronal populations to generate integrative homeostatic responses. We show that activity-dependent vasopressin release from hypothalamic neuroendocrine neurons in the paraventricular nucleus stimulates neighboring (∼100 μm soma-to-soma) presympathetic neurons, resulting in a sympathoexcitatory population response. This interpopulation crosstalk was engaged by an NMDA-mediated increase in dendritic Ca2+, influenced by vasopressin’s ability to diffuse in the extracellular space, and involved activation of CAN channels at the target neurons. Furthermore, we demonstrate that this interpopulation crosstalk plays a pivotal role in the generation of a systemic, polymodal neurohumoral response to a hyperosmotic challenge. Because dendritic release is emerging as a widespread process, our results suggest that a similar mechanism could mediate interpopulation crosstalk in other brain systems, particularly those involved in generating complex behaviors.Video Abstrac