Miracle-dz/UniFAR-FTUs huggingface dataset:
A Quantitative Description of Dendritic Conductances and Its Application to Dendritic Excitation in Layer 5 Pyramidal Neurons

Postsynaptic integration is a complex function of passive membrane properties and nonlinear activation of voltage-gated channels. Some cortical neurons express many voltage-gated channels, with each displaying heterogeneous dendritic conductance gradients. This complexity has hindered the construction of experimentally based mechanistic models of cortical neurons. Here we show that it is possible to overcome this obstacle. We recorded the membrane potential from the soma and apical dendrite of layer 5 (L5) pyramidal neurons of the rat somatosensory cortex. A combined experimental and numerical parameter peeling procedure was implemented to optimize a detailed ionic mechanism for the generation and propagation of dendritic spikes in neocortical L5 pyramidal neurons. In the optimized model, the density of voltage-gated Ca2+ channels decreased linearly from the soma, and leveled at the distal apical dendrite. The density of the small-conductance Ca2+-activated channel decreased along the apical dendrite, whereas the density of the large-conductance Ca2+-gated K+ channel was uniform throughout the apical dendrite. The model predicted an ionic mechanism for the generation of a dendritic spike, the interaction of this spike with the backpropagating action potential, the mechanism responsible for the ability of the proximal apical dendrite to control the coupling between the axon and the dendrite, and the generation of NMDA spikes in the distal apical tuft. Moreover, in addition to faithfully predicting many experimental results recorded from the apical dendrite of L5 pyramidal neurons, the model validates a new methodology for mechanistic modeling of neurons in the CNS.
Evaluation of children in six blind schools of Andhra Pradesh.

PURPOSE 1. To determine the anatomical site and underlying causes of severe visual impairment and blindness in children in special education in Andhra Pradesh, India. 2. To compare the causes of blindness in two different regions in the state. 3. To evaluate improvement with correction of refractive error and low-vision devices (LVDs). METHODS Children in 6 schools for the blind and in 3 integrated education programmes were examined by one ophthalmologist, and were refracted and assessed for LVDs by an optometrist. The major anatomical site and underlying aetiology of severe visual impairment and blindness (SVI/BL; < 6/60 in the better eye) were recorded using the standardised WHO reporting form. RESULTS Two hundred and ninety one students under 16 years were examined, and after refraction, 267 (91.7%) were classified as being severely visually impaired or blind. The most common anatomical sites of SVI/BL were retina in 31.1% children; cornea in 24.3%; and whole globe in 20.2%. The aetiology was unknown in 38.2%, hereditary in 34.8% and childhood causes in 24%. 114 children (39.2%) had functional low vision (i.e. visual acuity < 6/18 to light perception with navigational vision). In this group, 36 children improved with spectacles and 16 benefited by LVDs. 41 children (15.4%) were able to read N10 point though they were studying Braille. CONCLUSION Overall 37.4% of children had "avoidable" causes of blindness. The major avoidable causes were vitamin-A deficiency and cataract. Vitamin-A deficiency and congenital anomalies were more common in the dry plateau areas of the state. One in seven children could read normal print with optical support.
The BRCA1 Variant p.Ser36Tyr Abrogates BRCA1 Protein Function and Potentially Confers a Moderate Risk of Breast Cancer

The identification of variants of unknown clinical significance (VUS) in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02) in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.
Inhibition of Human Immunodeficiency Virus Type 1 Replication in Primary CD4+ T Lymphocytes, Monocytes, and Dendritic Cells by Cytotoxic T Lymphocytes

ABSTRACT We demonstrate that human immunodeficiency virus type 1 (HIV-1)-specific CD8+ cytotoxic T lymphocytes (CTL) suppress HIV-1 replication in primary lymphocytes, monocytes, and dendritic cells individually. Viral inhibition is significantly diminished in lymphocyte-dendritic cell clusters, suggesting that these clusters in vivo could be sites where viral replication is more difficult to control by CTL.
A private allele ubiquitous in the Americas

The three-wave migration hypothesis of Greenberg et al. has permeated the genetic literature on the peopling of the Americas. Greenberg et al. proposed that Na-Dene, Aleut-Eskimo and Amerind are language phyla which represent separate migrations from Asia to the Americas. We show that a unique allele at autosomal microsatellite locus D9S1120 is present in all sampled North and South American populations, including the Na-Dene and Aleut-Eskimo, and in related Western Beringian groups, at an average frequency of 31.7%. This allele was not observed in any sampled putative Asian source populations or in other worldwide populations. Neither selection nor admixture explains the distribution of this regionally specific marker. The simplest explanation for the ubiquity of this allele across the Americas is that the same founding population contributed a large fraction of ancestry to all modern Native American populations.
Comparing the Effects of Morphine Sulfate and Diclofenac Suppositories on Postoperative Pain in Coronary Artery Bypass Graft Patients

Background: Simple and efficient way of pain management after Coronary Artery Bypass Graft (CABG) surgery is an important aspect of patients' care. Objectives: This study aimed to compare the effects of morphine and diclofenac suppositories on postoperative pain management. Patients and Methods: In this double-blinded clinical trial study, 120 patients aged 30-65 years old, undergone CABG, were equally divided into two groups of A (morphine) and B (diclofenac). All patients were anesthetized with intravenous fentanyl 10 μg/kg, etomidate 0.2 mg/kg and cisatracurium 0.2 mg/kg. Anesthesia was maintained with oxygen 50% and air 50%, propofol 50 μg/kg/min, fentanyl 1-2 μg/kg/h and atracurium 0.6 mg/kg/h. Analgesics were administered after the operation at intensive care unit (ICU) and Visual Analogue Score (VAS) was evaluated in both groups in 4-hour intervals after extubation for 24 hours. After extubation in case of VAS > 3, morphine suppository 10 mg (group A) or diclofenac suppository 50 mg (group B) was administered for patients. Results: No significant statistical relationship was found between the two groups regarding gender, age, BMI, paracetamol consumption, length of operation time, cardiopulmonary bypass pump (CPB) time, and stay time at ICU (P Value ≥ 0.05). Total dosage of used morphine was 22 ± 8.3 mg in each patient and total dosage of used diclofenac was 94 ± 32.01 mg. Average variation of VAS at measured intervals was significant (P Value ≤ 0.0001), but these variations were not significantly different when comparing the two groups (P Value = 0.023). Conclusions: Both morphine and diclofenac suppositories reduced pain significantly and similarly after CABG surgery.
Toxoplasma gondii Chromodomain Protein 1 Binds to Heterochromatin and Colocalises with Centromeres and Telomeres at the Nuclear Periphery

Background Apicomplexan parasites are responsible for some of the most deadly parasitic diseases afflicting humans, including malaria and toxoplasmosis. These obligate intracellular parasites exhibit a complex life cycle and a coordinated cell cycle-dependant expression program. Their cell division is a coordinated multistep process. How this complex mechanism is organised remains poorly understood. Methods and Findings In this study, we provide evidence for a link between heterochromatin, cell division and the compartmentalisation of the nucleus in Toxoplasma gondii. We characterised a T. gondii chromodomain containing protein (named TgChromo1) that specifically binds to heterochromatin. Using ChIP-on-chip on a genome-wide scale, we report TgChromo1 enrichment at the peri-centromeric chromatin. In addition, we demonstrate that TgChromo1 is cell-cycle regulated and co-localised with markers of the centrocone. Through the loci-specific FISH technique for T. gondii, we confirmed that TgChromo1 occupies the same nuclear localisation as the peri-centromeric sequences. Conclusion We propose that TgChromo1 may play a role in the sequestration of chromosomes at the nuclear periphery and in the process of T. gondii cell division.
Effect of venous dexamethasone, oral caffeine and acetaminophen on relative frequency and intensity of postdural puncture headache after spinal anesthesia

Background: Postdural puncture headache (PDPH) is a relatively common complication after regional anesthesia, especially in younger people, bothersome to patients and needs prophylaxis to prevent this complication. This study was conducted aiming to determine the preventive effect of dexamethasone plus caffeine and acetaminophen on relative frequency and intensity of PDPH after spinal anesthesia. Materials and Methods: In a clinical trial study, 90 candidates for the lower extremities orthopedic elective operation were divided into two groups of 45 individuals each. Intervention group received the compound of 500 mg acetaminophen +65 mg oral caffeine +8 mg venous dexamethasone an hour before spinal blocking, and the control group received placebo tablets + a dexamethasone equivalent volume of venous normal saline. The level of postoperative headache at the time of entrance to recovery and discharge, 6, 12, 24, 48, and 72 h postoperatively were measured based on Visual Analog Scale criterion in the two groups and then compared with each other. Results: During the study, 24 patients in the control group and 17 patients in the intervention group were afflicted with headache; however, with no significant difference (P = 0.14). Total frequency of headache incidence was 35 times in the control group and 27 times in the intervention group (P = 0.32). Conclusions: Though the taking of acetaminophen + caffeine + dexamethasone is associated with a decrease in headache intensity and duration and decrease in PDPH incidence, compared with placebo, however, no essentially and statistically significant effect was produced.
The constriction of the ductus arteriosus caused by oxygen and by asphyxia in newborn lambs

Since the beginning of this century it has been recognized that closure of the ductus arteriosus at birth occurs in two stages, a rapid constriction of the vessel which is later followed by gradual anatomical obliteration of its lumen over a period of weeks (Gerard, 1900 a, b; Wells, 1908). Recently it has been shown that, in the newborn lamb, the constriction which normally occurs within 5-20 min of birth does not at once lead to complete obliteration of the lumen. Blood continues to flow through the constricted lumen at high velocity, and this flow gives rise to the characteristic murmur and thrill over the junction of ductus arteriosus and pulmonary trunk (Dawes, Mott & Widdicombe, 1955 a, b). The appearance of this murmur in unanaesthetized, spontaneously breathing lambs is therefore a useful indication of constriction of the ductus arteriosus. In anaesthetized lambs in which the chest has been opened, changes in the external diameter of the ductus arteriosus may be measured directly under a variety of experimental conditions. The appearance of the murmur and direct measurement of the ductus have been used in this paper to test the various conflicting theories of the mechanism whereby the ductus constricts shortly after birth: a preliminary account of the observations has already been published (Born, Dawes, Mott & Rennick, 1955).
Phylogeographical history of the sponge Crambe crambe (Porifera, Poecilosclerida): range expansion and recent invasion of the Macaronesian islands from the Mediterranean Sea

We studied sequence variation in the nuclear ribosomal internal transcribed spacers (ITS‐1 and ITS‐2) in 111 individuals from 11 populations/localities of the sponge Crambe crambe across the core species range in the western Mediterranean Sea and Atlantic Ocean. We report the first confirmed instance of intragenomic variation in sponges. Phylogeographical, nested clade and population genetic analyses were used to elucidate the species’ evolutionary history. The study revealed highly structured populations affected by restricted gene flow and isolation‐by‐distance. A contiguous range expansion in the whole distribution area of the sponge was inferred. Phylogenetic analyses indicate a recent origin of most sequence types that could be explained by a recent origin of the species or a by recent bottleneck event in the studied area. A recent expansion of the distribution range to the Macaronesian region from the Mediterranean Sea was also detected, suggesting that C. crambe was recently introduced from the Mediterranean Sea to the Atlantic Ocean via human‐mediated transport, and that the pattern observed is not the result of a natural biogeographical relationship between these zones.
Parental smoking and lung function in children: an international study.

RATIONALE Both prenatal and postnatal passive smoking have been linked with respiratory symptoms and asthma in childhood. Their differential contributions to lung function growth in the general children's population are less clear. OBJECTIVE To study the relative impact of pre- and postnatal exposure on respiratory functions of primary school children in a wide range of geographic settings, we analyzed flow and volume data of more than 20,000 children (aged 6-12 yr) from nine countries in Europe and North America. METHODS Exposure information had been obtained by comparable questionnaires, and spirometry followed a protocol of the American Thoracic Society/European Respiratory Society. Linear and logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytic tools. MAIN RESULTS Smoking during pregnancy was associated with decreases in lung function parameters between -1% (FEV1) and -6% maximal expiratory flow at 25% of vital capacity left (MEF25). A 4% lower maximal midexpiratory flow (MMEF) corresponded to a 40% increase in the risk of poor lung function (MMEF < 75% of expected). Associations with current passive smoking were weaker though still measurable, with effects ranging from -0.5% (FEV1) to -2% maximal expiratory flow (MEF50). CONCLUSIONS Considering the high number of children exposed to maternal smoking in utero and the even higher number exposed to passive smoking after birth, this risk factor for reduced lung function growth remains a serious pediatric and public health issue.
Depth of cut models for multipass abrasive waterjet cutting of alumina ceramics

Predictive models for the depth of cut in multipass abrasive waterjet (AWJ) cutting of alumina ceramics are presented. Cutting operations both with and without nozzle oscillation are considered. The modelling process starts with the single pass cutting using a dimensional analysis technique and the particle erosion theories applied to alumina ceramics, before progressing to the development of the models for multipass cutting. The models are finally assessed both qualitatively and quantitatively when cutting an 87% alumina ceramic. It is shown that the model predictions are in good agreement with the experimental data with less than 1% of average errors.
Robust Real-Time Visual Odometry with a Single Camera and an IMU

The increasing demand for real-time high-precision Visual Odometry systems as part of navigation and localization tasks has recently been driving research towards more versatile and scalable solutions. In this paper, we present a novel framework for combining the merits of inertial and visual data from a monocular camera to accumulate estimates of local motion incrementally and reliably reconstruct the trajectory traversed. We demonstrate the robustness and efficiency of our methodology in a scenario with challenging camera dynamics, and present a comprehensive evaluation against ground-truth data.
Structural perturbations in DNA caused by bis-intercalation of ditercalinium visualised by atomic force microscopy

Atomic force microscopy (AFM) has been used to examine perturbations in the tertiary structure of DNA induced by the binding of ditercalinium, a DNA bis-intercalator with strong anti-tumour properties. We report AFM images of plasmid DNA of both circular and linearised forms showing a difference in the formation of supercoils and plectonemic coils caused at least in part by alterations in the superhelical stress upon bis-intercalation. A further investigation of the effects of drug binding performed with 292 bp mixed-sequence DNA fragments, and using increment in contour length as a reliable measure of intercalation, revealed saturation occurring at a point where sufficient drug was present to interact with every other available binding site. Moment analysis based on the distribution of angles between segments along single DNA molecules showed that at this level of bis-intercalation, the apparent persistence length of the molecules was 91.7 +/- 5.7 nm, approximately twice as long as that of naked DNA. We conclude that images of single molecules generated using AFM provide a valuable supplement to solution-based techniques for evaluation of physical properties of biological macromolecules.
Prospective audit of treatment of paediatric febrile neutropenia in Australasia

Objectives: Febrile neutropenia post‐chemotherapy continues to impose a burden of morbidity and mortality on patients and families affected by childhood cancer, whereas these unplanned hospital admissions increase the financial cost of treating paediatric malignancies. There are currently no published national guidelines. This study comprises the first audit of current therapeutic practice in Australasia.
Mosaic genome structure of simian immunodeficiency virus from west African green monkeys.

Elucidation of the phylogenetic origins of simian and human immunodeficiency viruses (SIV and HIV) is fundamental to the understanding of HIV pathogenesis and the spread of AIDS worldwide. In this study, we molecularly characterized multiple SIVAGM isolates from four different African green monkey species (vervet, grivet, sabaeus and tantalus monkeys). Phylogenetic analysis of partial (1 kb) env sequences indicated that all SIVAGM strains cluster together, and that they fall into four distinct sequence sub‐groups according to their species of origin. However, alignment of long terminal repeat sequences revealed that SIVs from West African sabaeus monkeys contain a structural feature (a duplication of the transactivation response element) thus far only found in otherwise highly divergent lentiviruses infecting sooty mangabeys (SIVSM) and humans (HIV‐2). To determine whether there were additional similarities with the SIVSM/HIV‐2 group, a full‐length replication competent sabaeus provirus was cloned and sequenced. In phylogenetic trees derived from the central and 3′ coding regions, the sabaeus virus clustered with SIVAGM isolates from other African green monkey species. However, in trees derived from the 3′ half of gag and the adjacent 5′ region of pol, the sabaeus virus grouped with the SIVSM/HIV‐2 lineage. These results indicated that the sabaeus virus comprised a mosaic genome which must have resulted from recombination of divergent lentiviruses in the distant past. A second, independent sabaeus isolate exhibited similar phylogenetic relationships, suggesting that all West African green monkey viruses share this complex evolutionary history. Taken together, these results indicate that African green monkeys have been infected with SIVAGM for very long periods of time, and that recombination and cross‐species transmission in the wild have contributed to the genetic complexity of primate lentiviruses.
Insights into the Evolutionary Features of Human Neurodegenerative Diseases

Comparative analyses between human disease and non-disease genes are of great interest in understanding human disease gene evolution. However, the progression of neurodegenerative diseases (NDD) involving amyloid formation in specific brain regions is still unknown. Therefore, in this study, we mainly focused our analysis on the evolutionary features of human NDD genes with respect to non-disease genes. Here, we observed that human NDD genes are evolutionarily conserved relative to non-disease genes. To elucidate the conserved nature of NDD genes, we incorporated the evolutionary attributes like gene expression level, number of regulatory miRNAs, protein connectivity, intrinsic disorder content and relative aggregation propensity in our analysis. Our studies demonstrate that NDD genes have higher gene expression levels in favor of their lower evolutionary rates. Additionally, we observed that NDD genes have higher number of different regulatory miRNAs target sites and also have higher interaction partners than the non-disease genes. Moreover, miRNA targeted genes are known to have higher disorder content. In contrast, our analysis exclusively established that NDD genes have lower disorder content. In favor of our analysis, we found that NDD gene encoded proteins are enriched with multi interface hubs (party hubs) with lower disorder contents. Since, proteins with higher disorder content need to adapt special structure to reduce their aggregation propensity, NDD proteins found to have elevated relative aggregation propensity (RAP) in support of their lower disorder content. Finally, our categorical regression analysis confirmed the underlined relative dominance of protein connectivity, 3′UTR length, RAP, nature of hubs (singlish/multi interface) and disorder content for such evolutionary rates variation between human NDD genes and non-disease genes.