Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial permeability transition-pore inhibition enhances functional recovery after long-time hypothermic heart preservation

Objectives. Long-time preservation of the donor heart before transplantation is associated with mitochondrial damages resulting in functional deterioration after transplantation, although the exact mechanism behind this is still uncertain. Here, we have demonstrated the opening of a nonspecific pore in the inner membrane of the mitochondria, the mitochondrial permeability transition pore (PTP), as one of the reasons responsible for this functional deterioration. Methods. After 30 minutes of perfusion with the Krebs Henseleit buffer at 37°C in working mode, hearts from Wistar rats were arrested with ice-cold St. Thomas cardioplegic solution and preserved University of Wisconsin solution at 4°C with or without inhibiting the PTP with cyclosporin A (CsA) (0.2 &mgr;M). After 12 hours, the hearts were reperfused for 60 minutes at 37°C with or without perfusing the hearts during first 15 minutes of reperfusion with PTP openers lonidamine (30 &mgr;M) or atractyloside (20 &mgr;M). Results. Inhibiting PTP with CsA resulted in (a) significant recovery of cardiac functions, (b) well-preserved myocardial adenosine triphosphate (ATP) levels (P <0.001), (c) less myocardial water content (P <0.01), (d) less mitochondrial swelling and cytochrome C release, and (e) up-regulation of Bcl-2 expression compared with the control hearts without PTP inhibition. These effects are completely inhibited on opening the PTP before preservation, resulting in poor recovery of cardiac functions, loss of myocardial ATP, and severe mitochondrial swelling. Conclusion. The present study demonstrates the potential role of mitochondrial PTP after long- time hypothermic preservation of the heart, and therefore, regulation of PTP would prolong the preservation time of donor hearts.
Early thalamic lesions in patients with sleep-potentiated epileptiform activity

Objective: To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). Methods: We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) ≥1 brain MRI scan, and 3) ≥1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was ≥50% than spike percentage during wakefulness. Results: One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). Conclusions: Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA.
Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immunity

The immune system of vertebrate species consists of many different cell types that have distinct functional roles and are subject to different evolutionary pressures. Here, we first analysed gene conservation of all major immune cell types in human and mouse. Our results revealed higher gene turnover and faster evolution of trans-membrane proteins in NK cells compared to other immune cell populations, and especially T cells, but similar conservation of nuclear and cytoplasmic protein coding genes. To validate these findings in a distant vertebrate species, we used single-cell RNA-Sequencing of lck:GFP cells in zebrafish to obtain the first transcriptome of specific immune cell types in a non-mammalian species. Unsupervised clustering and single-cell TCR locus reconstruction identified three cell populations, T-cells, a novel type of NK-like cells and a smaller population of myeloid-like cells. Differential expression analysis uncovered new immune cell specific genes, including novel immunoglobulin-like receptors, and neofunctionalization of recently duplicated paralogs. Evolutionary analyses confirmed a higher gene turnover and lower conservation of trans-membrane proteins in NK cells compared to T cells in fish species, suggesting that this is a general property of immune cell types across all vertebrates.
Downstream modulation of North Pacific atmospheric river activity by East Asian cold surges

An East Asian cold surge (EACS) is characterized by rapid advancement of a polar airmass toward the east coast of the Eurasian continent in boreal winter. Over the east coast of Asia, extratropical cyclogenesis and the amplitudes of atmospheric disturbances ranging from synoptic to subseasonal timescales are immediately enhanced as the cold air approaches. This study investigates for the first time the impact of these EACS‐excited disturbances on the activity of atmospheric rivers (ARs) over the North Pacific. Applying a new AR detection algorithm to the NASA MERRA dataset, we show that the daily occurrence probability of ARs over the eastern North Pacific near the west coast of U.S. is effectively modulated by EACS. In particular, this downstream dynamical modulation goes through two distinct stages: during the period Day 0–3, where Day 0 corresponds to the time of the peak intensity of an EACS event, high‐frequency (HF, <6‐day) baroclinic disturbances developed over the western North Pacific and Gulf of Alaska lead to significant poleward moisture transport over these two regions, and during the period Day 4–6, intermediate‐low frequency (IF‐LF, >12‐day) barotropic disturbances developed from the merging of high‐frequency troughs increase the daily occurrence probability of ARs near the west coast of the U.S. by 50%, relative to the climatological value. The results reported here demonstrate the critical role of IF and LF disturbances in establishing the link between the predictability of EACS and that of the AR‐related extreme precipitation events in the western U.S. in boreal winter.
Sequential organogenesis sets two parallel sensory lines in medaka

Animal organs are typically formed during embryogenesis by following one specific developmental programme. Here, we report that neuromast organs are generated by two distinct and sequential programmes that result in parallel sensory lines in medaka embryos. A ventral posterior lateral line (pLL) is composed of neuromasts deposited by collectively migrating cells whereas a midline pLL is formed by individually migrating cells. Despite the variable number of neuromasts among embryos, the sequential programmes that we describe here fix an invariable ratio between ventral and midline neuromasts. Mechanistically, we show that the formation of both types of neuromasts depends on the chemokine receptor genes cxcr4b and cxcr7b, illustrating how common molecules can mediate different morphogenetic processes. Altogether, we reveal a self-organising feature of the lateral line system that ensures a proper distribution of sensory organs along the body axis. Summary: Two parallel sensory lines in medaka share a common origin and are composed of identical organs that are, nevertheless, generated through different morphogenetic programmes.
Regional Distribution of Extracellular 5‐Hydroxytryptamine and 5‐Hydroxyindoleacetic Acid in the Brain of Freely Moving Rats

Abstract: The extracellular concentrations of 5‐hydroxytryptamine (5‐HT) and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) have been determined in six brain areas of awake rats (frontal cortex, striaturn, hypothalamus, hippocampus, inferior colliculus, and raphe nuclei) using intracerebral microdialysis. The extracellular levels of 5‐HT showed no significant differences among the brain regions studied. The tissue levels of 5‐HT and 5‐HIAA as well as the extracellular concentration of 5‐HIAA were significantly higher in raphe nuclei. The regional distribution of tissue and extracellular 5‐HIAA were very similar, suggesting that extracellular 5‐HIAA depends mainly on the output from the intracellular compartment. On the other hand, extracellular 5‐HT and tissue 5‐HT showed a different distribution pattern. The tissue/extracellular ratio for 5‐HT ranged from 739 in frontal cortex to 2,882 in raphe, whereas it only amounted to 1.8–3.6 for 5‐HIAA. The relationship between the present results and the density of 5‐HT uptake sites in these areas is discussed.
Oral care.

Fatima presents the situation in Cambodgia. This country with a population of 14 000 000 has 420 dentists and 250 nurses specialized in dentistry. There are dental offices in the capital, but not in the rural areas. Access to dental therapies is unequal. Dental hygiene in the rural areas is very limited. Polluted waters and the lack of professional dental care leads to loss of teeth and severe periodontal diseases. The main solution for improving the population’s oral health would be education, by instilling habits of oral hygiene such as the regular brushing of teeth.
Insomnia types and sleep microstructure dynamics

This work aims to investigate sleep microstructure as expressed by Cyclic Alternating Pattern (CAP), and its possible alterations in pathological sleep. Three groups, of 10 subjects each, are considered: a) normal sleep, b) psychophysiological insomnia, and c) sleep misperception. One night sleep PSG and sleep macro- micro structure annotations were available per subject. The statistical properties and the dynamics of CAP events are in focus. Multiscale and non-linear methods are presented for the analysis of the microstructure event time series, applied for each type of CAP events, and their combination. The results suggest that a) both types of insomnia present CAP differences from normal sleep related to hyperarousal, b) sleep misperception presents more extensive differences from normal, potentially reflecting multiple sleep mechanisms, c) there are differences between the two types of insomnia as regard to the intertwining of events of different subtypes. The analysis constitutes a contribution towards new markers for the quantitative characterization of insomnia, and its subtypes.
Therapeutic Role of Innovative Anti-Inflammatory Medications in the Prevention of Acute Coronary Syndrome

An improved understanding of the pathogenesis of acute coronary syndromes and its relationship to atherosclerotic plaque rupture and thrombosis has contributed to the investigation of novel therapies for prevention and treatment. New data ascribe an increasingly important role of active inflammation in contributing to thinning of the atherosclerotic fibrous cap and plaque instability. Despite this understanding, there are currently no therapeutic approaches to specifically target the unstable plaque. Multiple randomized trials investigating treatment strategies have recently been completed or are currently being conducted, using anti-inflammatory medications, such as methotrexate, colchicine, darapladib, varespladib, losmapimod, and canakinumab, to reduce the incidence of cardiovascular events including acute coronary syndromes. These anti-inflammatory medications differ in their mechanism of action from having widespread targets (as is the case for methotrexate and colchicine) to having specific targets (as is the case for darapladib, varespladib, losmapimod, and canakinumab). The trials investigating the efficacy of darapladib in reducing cardiovascular events revealed no significant benefit when compared with the current standard of care. The varespladib studies were terminated early because of adverse outcomes. However, the outcomes of the remaining drug studies may still contribute to novel therapeutic approaches in the treatment of patients with unstable coronary artery disease.
Sex and Ageing: The Role of Sexual Recombination in Longevity

I use a set of machines based on the concept of nested rule systems built on the a modified version of the Wolfram elemental cellular automata to investigate the role of recombination in providing resistance to ageing. Class III and class IV machines are observed to respond differently to recombination. Class IV machines show recombinational centring in their neutral networks whereas class III machines respond negatively to recombination. Rule 110 shows a unusual response to recombination. Recombination selects for resistance to recombination, the population moves to regions of genome space with high redundancy, this results in organisms with highly robust genomes, more likely to complete development and to be long lived. The increase in longevity may be sufficient to compensate for the costs of sex, including the two fold cost of sex, through increased reproductive potential in long lived organisms requiring long maturation times. Large complex species should therefore be resistant to invasion by asexual mutants whereas small simple organisms with early maturation should be vulnerable to invasion by asexual forms.
Immunolocalization of the gamma isoform of nonmuscle actin in cultured cells

In many vertebrate nonmuscle cells, the microfilament subunit protein, actin, exists as two isoforms, called beta and gamma, whose sequences differ only in their amino-terminal regions. We have prepared a peptide antibody specifically reactive with the amino-terminal sequence of gamma actin. This antibody reacted with nonmuscle actin as determined by Western blots of SDS gels, and reacted with the gamma, but not the beta, nonmuscle actin isoform as shown by Western blots of isoelectric focusing gels. In immunofluorescence experiments, the gamma peptide antibody stained microfilament bundles, ruffled edges, and the contractile ring of a variety of cultured cells, including mouse L cells, which have previously been reported to contain only the beta actin isoform (Sakiyama, S., S. Fujimura, and H. Sakiyama, 1981, J. Biol. Chem., 256:31-33). Double immunofluorescence experiments using the gamma peptide antibody and an antibody reactive with all actin isoforms revealed no differences in isoform localization. Thus, at the level of resolution of light microscopy, we have detected the gamma actin isoform in all microfilament-containing structures in cultured cells, and have observed no subcellular sorting of the nonmuscle actin isoforms.
Novel STAT3 Target Genes Exert Distinct Roles in the Inhibition of Mesoderm and Endoderm Differentiation in Cooperation with Nanog

Leukemia inhibitory factor (LIF) activates the transcription factor signal transducer and activator of transcription 3 (STAT3), which results in the maintenance of mouse embryonic stem cells in the pluripotent state by inhibiting both mesodermal and endodermal differentiation. How the LIF/STAT3 pathway inhibits commitment to both mesoderm and endoderm lineages is presently unknown. Using a hormone‐dependent STAT3 and with microarray analysis, we identified 58 targets of STAT3 including 20 unknown genes. Functional analysis showed that 22 among the 23 STAT3 target genes analyzed contribute to the maintenance of the undifferentiated state, as evidenced by an increase in the frequency of differentiated colonies in a self‐renewal assay and a concomitant elevation of early differentiation markers upon knockdown. Fourteen of them, including Dact1, Klf4, Klf5, Rgs16, Smad7, Ccrn4l, Cnnm1, Ocln, Ier3, Pim1, Cyr61, and Sgk, were also regulated by Nanog. Analysis of lineage‐specific markers showed that the STAT3 target genes fell into three distinct categories, depending on their capacity to inhibit either mesoderm or endoderm differentiation or both. The identification of genes that harness self‐renewal and are downstream targets of both STAT3 and Nanog shed light on the mechanisms underlying functional redundancy between STAT3 and Nanog in mouse embryonic stem cells. STEM CELLS 2009;27:1760–1771
Prediction Error Associated with the Perceptual Segmentation of Naturalistic Events

Predicting the near future is important for survival and plays a central role in theories of perception, language processing, and learning. Prediction failures may be particularly important for initiating the updating of perceptual and memory systems and, thus, for the subjective experience of events. Here, we asked observers to make predictions about what would happen 5 sec later in a movie of an everyday activity. Those points where prediction was more difficult corresponded with subjective boundaries in the stream of experience. At points of unpredictability, midbrain and striatal regions associated with the phasic release of the neurotransmitter dopamine transiently increased in activity. This activity could provide a global updating signal, cuing other brain systems that a significant new event has begun.
Effects of culture, sex, and age on the distribution of handedness: An evaluation of the sensitivity of three measures of handedness

The present study examined the effects of culture, age, and sex on three measures of handedness: writing hand, Annett's primary handedness items, and a measure based on hand preference for 11 activities. Using data from a large international study, the relationship between the culture in which participants learned to write (as defined by Hofstede's cultural dimensions) and adult handedness was examined. Participants who learned to write in formal cultures were less likely to be classified as left‐handed than those who learned in less formal cultures. Older participants and those who learned to write in formal cultures were more likely to be classified as left‐handed by the Annett and 11 item measures than by the writing hand classification. Across measures females were less likely to be classified as left‐handed than males. Handedness for writing was found to be more sensitive to cultural influences than the other measures. These results suggest that some measures of handedness may be more sensitive to specific handedness aetiologies than others.
COSMIC RAY ORIGIN IN OB ASSOCIATIONS AND PREFERENTIAL ACCELERATION OF REFRACTORY ELEMENTS: EVIDENCE FROM ABUNDANCES OF ELEMENTS 26Fe THROUGH 34Se

We report abundances of elements from 26Fe to 34Se in the cosmic radiation measured during fifty days of exposure of the Trans-Iron Galactic Element Recorder (TIGER) balloon-borne instrument. These observations add support to the concept that the bulk of cosmic ray acceleration takes place in OB associations, and they further support cosmic ray acceleration models in which elements present in interstellar grains are accelerated preferentially compared with those found in interstellar gas.
Morphological pattern of childhood solid tumours in Lagos University Teaching Hospital.

BACKGROUND There is a wide variation in the incidence of childhood tumors world wide. The relative incidence of childhood tumors in developing countries is increasing and might add significantly to the high childhood morbidity and mortality caused by infectious diseases. There is need to determine the incidence of childhood cancer in different centers of the country and contribute to the National cancer register. OBJECTIVE The aim of this study is to determine the burden and patterns of childhood tumour in our environment. METHODS A retrospective review of histologically diagnosed cases of childhood tumours seen from January 2000 to 2007 from the records of the Department of Morbid Anatomy of the Lagos University Teaching Hospital (LUTH), Nigeria was carried out. All the cases were analyzed for age and gender distribution as well as histological types. RESULTS Malignant tumours constituted 30.50% of the tumours of which retinoblastoma is the most common. The most common benign tumour was fibroadenoma accounting for 36.2% of all benign tumours. The female to male ratio for malignant and benign tumours are 1:1 and 1:1.3 respectively. The peak age incidence was 11 - 15 years for benign and 1 - 5 for malignant tumours. CONCLUSION The study showed decrease in the annual incidence of childhood tumours in Lagos. There was however no difference in the pattern when compared with other centers in Nigeria and in other African countries.
EVEREASON AND EVEPLIANCES: TOOLS FOR DRIVING INTERACTIONS USING ATTENTION-BASED REASONING

The prevailing ubiquity of computers has brought about a considerable increase in the number of digital appliances at our disposal. Such ubiquitous appliances, however, are still designed to act in isolation. Each appliance may independently notify the user of incoming communications or computer activity, without any consideration to the user's engagement or interaction with other devices or persons. Devices continue to relay volumes of email, instant messages, phone calls and appointment notifications, collectively producing an intricate web of annoying 'attention grabbers', within which a user can easily become quite entangled. This research proposes that by coordinating communications on the basis of user activity, availability, or more specifically user attention, devices may engage in more polite and respectful interaction with their users, without fragmenting their limited cognitive attention [48, 63]. Although designers of computer systems may be able to develop notification strategies that are less disruptive and better coordinated between devices and users, interruptions generated by computer systems are not the only source of interference with the user's focus task. Active human ad-hoc and co-located group communications may be equally distracting and problematic. This research explores how regulating communications by ubiquitous sensing and reasoning about the focal point of the user's communications may, in the future, alleviate such problems in homes and office scenarios. This is explored through the design of Attentive User Interfaces. Firstly, a personal communication server called EyeReason, which acts as a central receptionist that handles all direct and indirect interactions of a user with computers, and secondly, through the design of computing appliances, called EyePliances, which are sensitive to a user's attention. Our methods are analogous to human-tum taking in group communication. Just as tum-taking improves an individual's ability to conduct foreground processing of conversations [65], Attentive User Interfaces bridge the gap between the foreground and periphery of user activity, thereby facilitating users to move smoothly in between. By sensing a user's attention for objects and people in their everyday environment, and by treating user attention as a limited resource, EyeReason and EyePliances work together to avoid today's ubiquitous patterns of interruptions. Instead, they take turns for communication, by sensing when the user is paying attention to them before taking the floor.