Miracle-dz/UniFAR-FTUs huggingface dataset:
Where have the STEMIs gone during COVID-19 lockdown?

The coronavirus disease (COVID-19) outbreak has threatened to overwhelm European healthcare systems, potentially overshadowing other emergencies including ST-segment elevation myocardial infarction (STEMI) [1}. We analyzed the impact of the COVID-19 national lockdown on STEMI care in 3318 patients enrolled in the prospective France PCI registry between 15 January 2019 and 14 April 2020. The registry prospectively follows all patients undergoing coronary angiography at 12 interventional cardiology centers located in the western part of France which is coincidentally the area least impacted by the outbreak. The ethical aspects, basic methodology and rationale for the registry have been already described and published (2). Comparing monthly admission rates in the pre-COVID-19 group (enrolled before 15 March 2020, the date of national lockdown announcement) to rates post-lockdown, there was a 18 % drop in admissions for STEMI, from a median of 224 per month pre-COVID-19 to 184 per month in the COVID-19 group (p<0.001) (Figure) and spectacular drop of 25% between the month of March 2019 and March 2020 (p<0.003). The steep decline was found for both acute (<24 hrs) and late presentation (>24 hrs) STEMI. manuscript
Land use systems to improve carbon sequestration in soils for mitigation of climate change

The main objective of this study was to assess the carbon stocks and carbon dioxide sequestration under different land use systems within the same locality with four old cultivation. The soil samples were collected at a depth of 0-15cm, 15-30cm, 30-50 cm and 50-100 cm from a mango, cashew, rose, vegetable and medicinal and aromatic cropping systems. The study showed that, the magnitude of carbon sequestration is more under mango orchard followed by cashew orchard than annuals crops like rose, medicinal and aromatic and vegetable block. The carbon dioxide sequestration was significantly greater under the perennial crops as compared to annual crops. It was observed that perennial horticulture crops increases the soil organic carbon (SOC) and carbon dioxide storage than annual crops and reduce the carbon emissions to the atmosphere which helps to mitigate the global warming.
The Regulation of Mammalian Target of Rapamycin

i Acknowledgements ii Abbreviations iii Table of contents 1 Chapter 1. General Introduction 7 1.1 An introduction to mTOR 7 1.1.1 The complexity of mTOR complexes 7 1.1.2 Phosphorylation and function of mTORC components 8 1.2 Upstream regulators of mTOR 16 1.2. 1 Regulation of mTORC1 by growth factors 16 1.2. 2 Regulation of mTORC1 by amino acids 20 1.2. 3 Regulation of mTORC1 by energy status 23 1.2. 4 Regulation of mTORC1 by oxidative stress 25 1.2. 5 Regulation of mTORC1 by inflammation 26 1.2. 6 Regulation of mTORC1 by the Wnt pathway 27 1.2. 7 Regulation of mTOR by tumour suppressors 28 1.2. 8 Regulation of mTORC2 29 1.3 Downstream effectors of mTOR 32 1.3. 1 mTORC1 downstream targets 32 1.3. 2 mTORC2 downstream targets 43 1.4 Physiological roles of mTOR 46
Laboratory Investigations The Receptor Activator of Nuclear Factor-jB Ligand Inhibitor Osteoprotegerin Is a Bone-Protective Agent in a Rat Model of Chronic Renal Insufficiency and Hyperparathyroidism

Osteoprotegerin (OPG) acts by neutralizing the receptor activator of nuclear factor-jB ligand (RANKL), the primary mediator of osteoclast differen- tiation, function, and survival. We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT). SHPT was in- duced in rats by 5/6 nephrectomy (5/6 Nx) and a 1.2% P/ 0.6% Ca 2+ diet. Starting 1 week after 5/6 Nx, rats were treated with vehicle (veh) or OPG-Fc (3 mg/kg, intrave- nously) every 2weeks for 9 weeks. At baseline, 3, 6, and 9 weeks, blood was taken and bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual- energy X-ray absorptiometry. Serum parathyroid hor- mone (sPTH) levels reached 912pg/ml in 5/6 Nx rats vs. 97 pg/ml in shams at 9 weeks. OPG-Fc had no effect on sPTH or Ca 2+ levels throughout the 9-week study, indi- cating that SHPT was a renal effect independent of bone changes. At 3 weeks, 5/6 Nx-veh rats had osteopenia compared with sham-veh rats and 5/6 Nx-OPG-Fc rats had significantly higher percent changes in whole-body BMC, leg BMD, and lumbar BMD versus 5/6 Nx-veh rats. By 6-9 weeks, elevated sPTH was associated with reversal of bone loss and osteitis fibrosa in the proximal tibial metaphysis. OPG-Fc decreased this sPTH-driven high bone turnover, resulting in augmented thickness of proximal tibial trabeculae in 5/6 Nx rats. Thus, RANKL inhibition with OPG-Fc can block the deleterious effects of continuously elevated sPTH on bone, suggesting that RANKL may be an important therapeutic target for protecting bone in patients with CKD and SHPT.
Microflow-Based Device for In Vitro and Ex Vivo Drug Permeability Studies

This paper presents a novel microflow-based concept for studying the permeability of in vitro cell models or ex vivo tissues. Using the proposed concept, we demonstrate how to maintain physiologically relevant test conditions and produce highly reproducible permeability values for a range (31) of drug compounds. The apparent permeability coefficients (Papp) showed excellent correlation (0.89) with the values from experiments performed with a conventional Ussing chamber. Additionally, the microflow-based concept produces notably more concentrated samples than the conventional Ussing chamber-based approach, despite the fact that more than 10 times smaller quantities of test compounds and biological membranes are needed in the microflow-based concept.
Investigation of spatio-temporal coding in the olfactory bulb of larval Xenopus laevis using fast confocal imaging

The olfactory bulb (OB) is the only central processing station of the vertebrate olfactory system. It is assumed that odors are represented by a spatio-temporal code in the OB, with both the identity of the activated neurons and the temporal sequence of their activity patterns being stimulus-relevant parameters. An adequate investigation of these coding principles thus relies on the simultaneous recording of a large number of cells with a high temporal resolution. To date, few studies have been based on recordings of this type, and even less have attempted to investigate and quantify aspects of inter-neuronal dependencies in the odor evoked activity patterns. A fast confocal microscope was designed, built, characterized, and subsequently used to study inter-cellular dependencies in neuronal activity patterns, which would be obscured by inter-trial variability in successive single-cell recordings. Specifically, the onset times of odor-evoked activity in ensembles of mitral/tufted cells in the Xenopus larvae OB were investigated, visualized using the Ca2+ indicator dye Fluo-4. A novel measure, the inversion index, was introduced to quantify the similarity in the order of response onsets between pairs of stimulus applications. Using this measure, it could be shown that these patterns are highly reproducible between applications of a given odor, both for mono-molecular odorants and for complex mixtures. Additionally, the onset order was found to be highly informative about odor identity, while it only relies weakly on the odor concentration. These observations make the onset pattern of OB neurons a promising candidate for a stimulus-relevant feature of the code implemented in the OB. Relation to other properties of the olfactory system and possible decoding strategies are discussed. In a second application, the fast imaging system was used to acquire time series of image stacks of spontaneous activity in the OB. By exploiting the diverse temporal activity patterns as a means of intrinsic contrast, the individual neurons" dendritic morphology could be visualized. The result of this novel method, termed activity correlation imaging, is a high-contrast multi-color visualization of the neuronal network, as demonstrated on the mitral/tufted cells of the Xenopus larvae OB. Yielding both functional and structural information about neuronal populations, this method opens up unprecedented possibilities for the investigation of neuronal networks.
Association between Mental Disorders and Subsequent Medical Conditions.

BACKGROUND Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).
Gelsolin - A Regulator of Postsynaptic Actin Assembly and AMPA Receptor Expression

Dendritic spines are the postsynaptic contact sites for the majority of excitatory synapses in the brain. Synaptic activity influences the number, shape and motility of dendritic spines and these effects are likely mediated by dynamic actin filaments, which are highly concentrated in spine heads. Drugs that inhibit actin dynamics block spine motility and interfere with the development of longterm potentiation (LTP), a long-lasting increase in synaptic strength considered to be closely related to learning and memory. This suggests that actin may serve as a link between activity-induced modulation of synaptic transmission and long-term changes in synaptic morphology. Despite this evidence for the importance of actin dynamics in synaptic plasticity, very little is known about its regulation at the synapse. In particular the mechanisms linking synaptic activity to the actin cytoskeleton in dendritic spines are not well understood. The experiments described in this thesis were focused on gelsolin as a promising candidate for mediating synaptic activity to actin cytoskeleton in dendritic spines. It is shown here that exposure of cultured hippocampal neurons to glutamate results in the accumulation of gelsolin in dendritic spines. This effect is the consequence of activation of NMDA receptors and influx of Ca2+. It is also shown that the F-actin binding domain of gelsolin is necessary for its enrichment at postsynaptic sites. Further experiments showed that actin filaments are more vulnerable to disruption by glutamate stimulation in gelsolin over-expressing neurons. The disruption of actin filaments in these neurons is also dependent on NMDA receptor activation and Ca2+ influx. LTD-related electric field stimulation likewise increased the loss of filamentous actin in gelsolin expressing cells compared with untransfected cells. The disruption of actin filaments required the severing function of gelsolin, which is associated with the specific filament-severing domain (domain 1) of the gelsolin molecule. Severing of F-actin by active gelsolin reduces the amount of AMPA receptors (GluR1) associated with dendritic spines. These results indicate that gelsolin plays an important role in linking synaptic activity to the postsynaptic actin cytoskeleton. Our results are also consistent with evidence that activation of NMDA receptors and influx of calcium ions play a crucial role in regulating the actin cytoskeleton in dendritic spines and hence are involved in the regulation of postsynaptic glutamate receptor plasticity at excitatory synapses via a feedback mechanism. This could occur in both the developing and mature brain under both normal and pathologic conditions. Taken together, our data support a model in which activity-dependent targeting of proteins into dendritic spines is a major mechanism for regulating synaptic plasticity at excitatory synapses.
Herpetofauna of Mahenge Mountain, Tanzania : a window on African biogeography

Mahenge Mountain is part of the Eastern Arc Mountains in Tanzania. It is bordered by the Kilombero flood plain to the west and forms a continuous mountain block with the Mbarika to the south, lying close to the Udzungwa and Southern Highland Mountain blocks. The amphibian fauna of the forests of Mahenge Mountain has not been investigated until recent fieldwork carried out in the Sali Forest Reserve that has revealed a diverse forest fauna. In this study new records are reported, details of habitats are given and a checklist of the amphibians and reptiles of Mahenge Mountain are provided. In addition, biogeographical analyses were carried out to investigate patterns of spatial turnover in species. This was achieved by calculating the standard similarity index between the amphibian assemblages of the highland Mahenge Mountains (>850 m) and the lowland Kilombero floodplain (<400 m). The results show significant differences (62%) between the two areas, reflecting large altitudinal turnover in species between the widespread lowland fauna and the montane fauna. This is further emphasized by a comparison of transects in lowland Mozambique and highland Zimbabwe, which has a comparable similarity index measure of 54%, impressive when comparing the difference in distance and altitude between the two transects. The reasons for this marked lowland-highland differentiation in Tanzania are poorly understood. Concern is raised for the preservation of this highland endemic fauna in the light of continuing habitat destruction.
Fluctuating Attention to News and Financial Contagion: Theory and Evidence

Financial contagion occurs when return and volatility transmit between fundamentally unrelated sectors. We develop an equilibrium model showing that contagion arises because investors pay fluctuating attention to news. As a negative shock hits one sector, investors pay more attention to it. This raises the volatility of equilibrium discount rates resulting in simultaneous spikes in cross-sector correlations and volatilities. We test the economic mechanism of our model on large U.S. industries by decomposing their returns into discount-rate and cash-flow components. Consistent with the model's predictions, we find that fluctuating attention generates return and volatility spillovers between discount-rate components of industry returns.
Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties

Isofraxidin (7-hydroxy-6, 8-dimethoxy coumarin) (IF) is a hydroxy coumarin with several biological and pharmacological activities. The plant kingdom is of the most prominent sources of IF, which, among them, Eleutherococcus and Fraxinus are the well-known genera in which IF could be isolated/extracted from their species. Considering the complex pathophysiological mechanisms behind some diseases (e.g., cancer, neurodegenerative diseases, and heart diseases), introducing IF as a potent multi-target agent, which possesses several herbal sources and the multiple methods for isolation/purification/synthesis, along with the unique pharmacokinetic profile and low levels of side effects, could be of great importance. Accordingly, a comprehensive review was done without time limitations until February 2020. IF extraction methods include microwave, mechanochemical, and ultrasound, along with other conventional methods in the presence of semi-polar solvents such as ethyl acetate (EtOAc). In addition to the isolation methods, related synthesis protocols of IF is also of great importance. From the synthesis point of view, benzaldehyde derivatives are widely used as precursors for IF synthesis. Along with the methods of isolation and biosynthesis, IF pharmacokinetic studies showed hopeful in vivo results of its rapid absorption after oral uses, leading to different pharmacological effects. In this regard, IF targets varieties of inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs). thereby indicating anticancer, cardioprotective, and neuroprotective effects. This is the first review on the synthesis, biosynthesis, isolation, and pharmacokinetic and pharmacological properties of IF in combating different diseases.
Roughage as additional rooting substrates for pigs

Straw is frequently supplied as a rooting material to improve the welfare of pigs. In Denmark, organically raised slaughter pigs must have access to both straw and roughage. In order to evaluate whether roughage can he used as an appropriate rooting substrate for pigs, the effects of six different roughage types on pigs’ behaviour was examined. Pairs of 11-week-old pigs were placed in specially designed 4 m 2 pens. Each pen contained a self-feeder for cereal, a water bowl, a box for roughage, a straw- bedded area and a dunging area. Four replicates were carried out, each consisting of seven pairs of pigs. In each replicate, each pair of pigs was supplied with either whole-crop silage of oats, vetch and lupin ( Avena sativa, Vicia sativa, and Lupinus luteus (OVL), whole-crop silage of barley and peas ( Hordeum vulgare and Pisum sativum ssp. arvense ) (BP), whole-crop silage of clover and grass ( Trifolium repens and Lolium perenne (CG), green grass meal ( Poa ssp.) (GM), hay of clover and grass ( Trifolium repens and Lolium perenne (H), fodder beets ( Beta vulgaris ssp. vulgaris) (B), or no roughage (the control treatment) (CON). The pigs manipulated OVL for longer than the other roughage products ( P P P P = 0·065). Interestingly, OVL and B were the two products with the lowest dry-matter content. It may suggest that the amount of time spent manipulating roughage will depend considerably on the specific characteristics of the roughage offered, for instance dry matter content and complexity but probably also texture, smell and taste. In addition, the time spent manipulating other elements in the pen will depend on the type of roughage offered. In conclusion, the present study shows that some, but not all, types of roughage are suited as an enrichment of the pig’s environment.
The functional co-ordination of leaf morphology, nitrogen concentration, and gas exchange in40 wetland species

Abstract We grew 40 commonly co-occurring species of wetland herbs from eastern North America under uniform conditions to evaluate the overall pattern of interspecific variation in specific leaf mass (SLM), foliar nitrogen content, stomatal conductance (g), and internal leaf CO2 concentration (ci). While the relationship between any two of these traits that influence net photosynthetic rate is constrained to some degree, there is sufficient flexibility to allow the evolution of different but more or less equally effective interrelationships among these central elements of leaf form and function. We use contemporary techniques of structural equation modelling to describe the general nature of such evolutionary diversification in leaf form and function among these wetland plants. Our model essentially extends the Cowan-Farquhar model of stomatal regulation to include relationships between SLM and foliar nitrogen. The model can take two forms, with variables expressed as either per unit leaf area or per unit leaf mass. When variables are expressed on an areal basis, the model predicts that a species with a higher SLM will have a higher foliar nitrogen level. The foliar nitrogen level, in accordance with the Cowan-Farquhar model, in turn determines the dynamics of stomatal regulation in relation to the marginal cost of water loss relative to carbon gain. The dependence of stomatal regulation on foliar nitrogen also determines the maximal rates of stomatal conductance and net photosynthesis. Internal CO2 concentrations within the leaf follow as a necessary consequence of these interrelationships. This areal-based model describes the data for the 35 C3 wetland species well; the same basic model applies to the five C4 species in our sample, except for shifts in the quantitative effects of net photosynthetic rate and stomatal conductance on internal CO2 levels. When the variables are expressed on a mass basis, a slightly different model results, as net photosynthetic rate decreases directly with SLM and is not related to species level variation in either leaf nitrogen concentration or maximal stomatal conductance. Both forms of the model indicate the need to advance our understanding of the ecological and evolutionary basis for variation in SLM, including its association with traits such as leaf demography and canopy architecture as well as environmental characteristics of the habitats where particular species predominate.
An Amylase Producing Maltotriose from Bacillus subtilis

An amylase which produces maltotriose from starch as the main product was found in the culture filtrate of a strain of Bacillus subtilis newly isolated from soil. The enzyme was purified to almost complete homogeneity, as judged by disc electrophoresis in polyacrylamide gel, by means of ammonium sulfate fractionation, DEAE-Sepharose column chromatography and Sephadex gel filtration.The optimum pH and temperature of the enzyme were around 6~7 and 50°C, respectively. Metal ions such as Hg2+, Cu2+, Zn2+, Ni2+ and Fe2+ strongly inhibitied the enzyme activity. The molecular weight was found to be about 25,000 by gel filtration. The yields of maltotriose from short-chain amylose (DP 17), amylopectin, soluble starch and glycogen were about 69, 56, 56 and 40%, respectively.
Tumors of the Central Nervous System

The term epigenetics is used to describe the study of stable and heritable alterations in gene expression potential that arise during development and cell proliferation. Two epigenetic mechanisms have been thoroughly investigated in the past few years: DNA methylation and histone modifications. The failure of the maintenance of these heritable epigenetic marks can lead to inappropriate activation or inactivation of signaling pathways and result in disease, such as cancer. Promoters of tumor suppressor genes have been assessed for hypermethylation with a variety of techniques, both at specific loci or genome wide. Methylation of the MGMT gene, which favors treatment results with temozolomide, is a clear example of the influence of methylation in a specific gene in astrocytomas. At the clinical level, the emphasis is now on combining inhibitors of DNA methyl transferases and of histone deacetylases.