Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Therapeutic Approach to Treat Alzheimer’s Disease by Neurotrophic Support During the Period of Synaptic Compensation

Alzheimer’s disease (AD), at present, is considered an incurable disease and a major dilemma with no drug to stop or slow down its progression. Drugs that are currently available in the market are able to only transiently improve the clinical symptoms. The repeated failures in developing an effective drug has led to the suggestion that the medical intervention was probably too late to be effective since the pathology starts many years before the appearance of the clinical symptoms. Probably, at the time of the appearance of clinical symptoms the brain has undergone major neuronal and synaptic loss. Because of the uncertainty on when to use a prevention therapy, especially targeting amyloid-β (Aβ) and tau pathologies, interventions that rely on the regenerative capacity of the brain such as the modulation of the inherent neurogenesis and neuronal plasticity represent a promising therapeutic strategy. Such an approach can act both at early as well as late stages of the disease and remove the barrier of the time of intervention. In this article, we review studies mainly from our laboratory that show the merit of early intervention during the synaptic and neuronal compensation period where the brain still has the capacity to self-repair by offering neurotrophic support in reversing cognitive impairment, neuronal and synaptic deficits, Aβ, and tau pathologies and decreasing mortality in a transgenic mouse model of AD.
Absorption of calcium from tortilla meals prepared from low-phytate maize.

BACKGROUND Calcium fortification of maize has been achieved for millennia in Central America by the process of nixtamalization. Bioavailability of calcium is, however, compromised by phytate, which is present in large quantities in maize kernels and is only modestly reduced by nixtamalization. OBJECTIVE The objective was to compare the absorption of calcium from tortilla meals prepared from low-phytate maize with that from meals prepared from maize with typical phytate content. DESIGN At 1-mo intervals, 5 healthy adult women were fed 2 test meals of approximately 140 g tortillas in lieu of breakfast. On one occasion, the tortillas were prepared from maize with approximately 60% phytate reduction, and, on the other occasion, they were prepared from the matching isohybrid wild-type maize. Beginning midway through the test meal, (44)Ca (0.3 mg/kg body wt) was administered in water as an extrinsic label; (42)Ca (0.06 mg/kg body wt) was administered intravenously immediately after the test meal. Isotope ratios of (42)Ca to (43)Ca and of (44)Ca to (43)Ca were measured by inductively coupled plasma mass spectrometry in urine collected as an 8-h pool from the period 16-24 h after intravenous tracer administration and prepared by the oxalate precipitation method. Fractional absorption of calcium was determined by using a dual-isotope ratio technique. RESULTS Mean fractional absorption of calcium from tortillas prepared from the low-phytate maize (0.50 +/- 0.03) was significantly (P = 0.003) greater than that from tortillas prepared from the control maize (0.35 +/- 0.07). CONCLUSION The increase in the quantity of calcium absorbed could be of practical importance for calcium nutriture when the intake of dairy products is limited.
Cell Panel Profiling Reveals Conserved Therapeutic Clusters and Differentiates the Mechanism of Action of Different PI3K/mTOR, Aurora Kinase and EZH2 Inhibitors

Cancer cell line panels are important tools to characterize the in vitro activity of new investigational drugs. Here, we present the inhibition profiles of 122 anticancer agents in proliferation assays with 44 or 66 genetically characterized cancer cell lines from diverse tumor tissues (Oncolines). The library includes 29 cytotoxics, 68 kinase inhibitors, and 11 epigenetic modulators. For 38 compounds this is the first comparative profiling in a cell line panel. By strictly maintaining optimized assay protocols, biological variation was kept to a minimum. Replicate profiles of 16 agents over three years show a high average Pearson correlation of 0.8 using IC50 values and 0.9 using GI50 values. Good correlations were observed with other panels. Curve fitting appears a large source of variation. Hierarchical clustering revealed 44 basic clusters, of which 26 contain compounds with common mechanisms of action, of which 9 were not reported before, including TTK, BET and two clusters of EZH2 inhibitors. To investigate unexpected clusterings, sets of BTK, Aurora and PI3K inhibitors were profiled in biochemical enzyme activity assays and surface plasmon resonance binding assays. The BTK inhibitor ibrutinib clusters with EGFR inhibitors, because it cross-reacts with EGFR. Aurora kinase inhibitors separate into two clusters, related to Aurora A or pan-Aurora selectivity. Similarly, 12 inhibitors in the PI3K/AKT/mTOR pathway separated into different clusters, reflecting biochemical selectivity (pan-PI3K, PI3Kβγδ-isoform selective or mTOR-selective). Of these, only allosteric mTOR inhibitors preferentially targeted PTEN-mutated cell lines. This shows that cell line profiling is an excellent tool for the unbiased classification of antiproliferative compounds. Mol Cancer Ther; 15(12); 3097–109. ©2016 AACR.
Quantification of supercolonial traits in the yellow crazy ant, Anoplolepis gracilipes

Abstract Supercoloniality is a social structure displayed by many invasive ant species, but there has been surprisingly little research quantifying the extent to which individual species display traits underlying such social organisation. This study quantifies three traits for the yellow crazy ant, Anoplolepis gracilipes Smith (Hymenoptera: Formicidae): little or no aggression between workers from different nests; the exchange of workers among nests; and resource exchange among nests, as well as supercolony structure arising from patterns of distribution and density of detections. Supercolonies displayed a structural continuum from being small (< 10 ha) and “aggregated” with great continuity among detections through to being large (> 10,000 ha) and “diffuse” with little continuity among detections. Smaller supercolonies had greater ant densities than larger supercolonies. In laboratory trials, no aggression was observed between workers from different nests sourced from different supercolonies, and paired nests merged within 24 hours. Workers lacked nest fidelity by rapidly populating artificial nests containing alien queens. The daily worker turnover rate per nest was estimated to be below 20%. Resources were readily moved among nests, with a resource being detected up to 13 m away from a source within 24 hours, and as far as 32 m after four days. The rate and distance of resource movement increased with increasing worker and nest density. This research has demonstrated that A. gracilipes displays supercoloniality equivalent to that of the well-studied Argentine ant Linepithema humile. Quantification of these traits is required for other supercolonial species to improve our understanding of this social strategy, especially for invasive ants to aid in understanding factors that promote invasion success and to improve management.
Pulmonary sequestration of polymorphonuclear leukocytes released from bone marrow in bacteremic infection.

We examined the bone marrow response and the sequestration of polymorphonuclear leukocytes (PMNs) in lung using a bacteremic infection model in rabbits. PMNs were labeled with the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) in the bone marrow, and the bone marrow release and the sequestration of BrdU-labeled PMNs were measured using immunohistochemistry. A focal subcutaneous infection (S) was induced, and the bacteremia (B) was produced 4 h later with Streptococcus pneumoniae (S+B). This S+B group was compared with other groups with only subcutaneous infection or only bacteremia. The S+B group developed a profound leukopenia after the bacteremia that was associated with an increase in circulating BrdU-labeled PMNs. Morphometric studies showed more PMN sequestration in the lung of the S+B group compared with the others ( P < 0.05). Compared with unlabeled PMNs, BrdU-labeled PMNs, which represent newly released PMNs, preferentially sequestered in lung ( P< 0.05) and were slow to migrate into the infected tissues ( P < 0.05). We conclude that bacteremic infection is associated with an accelerated release of PMNs from the bone marrow and that these newly released PMNs preferentially sequester in lung and are slow to migrate into infected tissues.
O2 regulates surfactant protein A mRNA transcription and stability in human fetal lung in vitro.

The effect of O2 on surfactant protein (SP) A mRNA transcription and half-life was determined in midtrimester human fetal lung tissue cultured in either 20 (control) or 70% O2. Incubation of tissues in 70% O2 resulted in a 133% increase in SP-A mRNA transcription rate compared with control tissues. The SP-A mRNA half-life was increased by 54% in lung tissues cultured in 70% O2 vs. control tissues. Western blot analysis indicated a threefold increase in SP-A in the 70% O2 condition, demonstrating that O2 regulation of SP-A mRNA levels results in corresponding changes in SP-A levels. Primer extension assays were performed to determine whether the observed increase in SP-A mRNA levels is secondary to the preferential expression of one of the human SP-A genes, SP-A1 or SP-A2. Transcripts of both the SP-A1 and SP-A2 genes were increased ∼100% in tissues maintained in 70% O2 compared with control tissues. These data demonstrate that O2regulates human SP-A mRNA levels by both transcriptional and posttranscriptional mechanisms. Furthermore, because there is no differential effect of O2 on the expression of SP-A1 vs. SP-A2 mRNA, the properties of these genes that mediate regulation by O2 must be conserved between the two genes.
Apparent thermogenic effect of injected glucagon is not due to a direct effect on brown fat cells.

To examine the significance of brown adipose tissue for the thermogenic response to glucagon, we injected glucagon intraperitoneally into rats (that have glucagon-sensitive brown fat cells) and into hamsters (that have glucagon-insensitive brown fat cells). Although a thermogenic response to glucagon injection was apparently observed in rats, this response was not augmented by cold acclimation and was not dose dependent. Similar observations were made in hamsters. The thermogenic response could be fully blocked by prior injection of the β-adrenergic blocker propranolol. Thus no direct thermogenic response to injected glucagon could be demonstrated, and the thermogenic response observed was fully due to vehicle injection. However, glucagon injection was able to unmask mitochondrial [3H]GDP binding. As expected, isolated brown fat cells from rats and mice responded thermogenically to glucagon but brown fat cells from hamsters were unresponsive. The EC50 of the rat brown fat cells was high (5 nM); these cells also responded to secretin, with an EC50 of 22 nM. It was concluded that, in contrast to earlier observations, no thermogenic response to injected glucagon could be observed; this may be related to differences in glucagon preparations. Brown fat cells from certain species are, however, glucagon sensitive. It is uncertain whether glucagon is the endogenous agonist for these receptors, but the presence of the glucagon-responsive receptor indicates alternative means to norepinephrine for stimulation of brown adipose tissue thermogenesis and, probably, of recruitment.
High glucose contributes to the proliferation and migration of non-small-cell lung cancer cells via GAS5-TRIB3 axis

Despite the growing number of studies exhibiting an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. The present study was to investigate whether and how high glucose (HG) contributes to the proliferation and migration of non-small-cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptotic effect on NSCLC cells. Moreover, HG inhibited the expression of growth arrest-specific 5 (GAS5) in NSCLC cells but elevated the protein level of tribbles homolog 3 (TRIB3). GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG-induced proliferation, anti-apoptosis, and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis, and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC.
Autonomic control of skeletal muscle blood flow at the onset of exercise.

The purpose of this study was to determine whether the autonomic nervous system is involved in skeletal muscle vasodilation at the onset of exercise. Mongrel dogs ( n = 7) were instrumented with flow probes on both external iliac arteries. Before treadmill exercise at 3 miles/h, 0% grade, hexamethonium (10 mg/kg) and atropine (0.2 mg/kg) or saline was infused intravenously. Ganglionic blockade increased resting heart rate from 87 ± 5 to 145 ± 8 beats/min ( P < 0.01) and reduced mean arterial pressure from 100 ± 4 to 88 ± 5 mmHg ( P < 0.01). During steady-state exercise, heart rate was unaffected by ganglionic blockade (from 145 ± 8 to 152 ± 5 beats/min), whereas mean arterial pressure was reduced (from 115 ± 4 to 72 ± 4 mmHg; P < 0.01). Immediate and rapid increases in iliac blood flow and conductance occurred with initiation of exercise with or without ganglionic blockade. Statistical analyses of hindlimb conductance at 5-s intervals over the first 30 s of exercise revealed a statistically significant difference between the control and ganglionic blockade conditions at 20, 25, and 30 s ( P < 0.01) but not at 5, 10, and 15 s of exercise. Hindlimb conductance at 1 min of exercise was 9.21 ± 0.68 and 11.82 ± 1.32 ml ⋅ min-1 ⋅ mmHg-1for the control and ganglionic blockade conditions, respectively. Because ganglionic blockade did not affect the initial rise in iliac conductance, we concluded that the autonomic nervous system is not essential for the rapid vasodilation in active skeletal muscle at the onset of exercise in dogs. Autonomic control of skeletal muscle blood flow during exercise is manifested through vasoconstriction and not vasodilation.
Sympathetic inhibition, leptin, and uncoupling protein subtype expression in normal fasting rats.

To further investigate neural effects on leptin and uncoupling proteins (UCPs), we studied in vivo perturbations intended to block adrenergic input to peripheral tissues. We examined plasma leptin, leptin mRNA, and adipose and muscle UCP subtype mRNA in rats treated with α-methyl- p-tyrosine methyl ester (AMPT-ME), which inhibits catecholamine synthesis and 6-hydroxydopamine (6HDA), which is toxic to catecholinergic nerve terminals but, unlike AMPT-ME, does not enter the central nervous system. Intraperitoneal AMPT-ME, 250 mg/kg, was administered at 1800 and 0700 the following day, and rats were killed at 1200-1400. All rats were fasted with free access to water during this time. Intraperitoneal AMPT-ME increased plasma leptin by 15-fold, increased interscapular brown adipose tissue (IBAT) and epididymal fat leptin mRNA by 2- to 2.5-fold, and also increased plasma insulin and glucose concentrations. Intraperitoneal AMPT-ME decreased IBAT UCP-3 mRNA to 40% of control, while it increased epididymal adipose UCP-3 mRNA approximately twofold. Intravenous AMPT-ME, 250 mg/kg, administered to conscious rats for 5 h decreased lumbar sympathetic nerve activity, increased plasma leptin (5.89 ± 1.43 compared with 2.75 ± 0.31 ng/ml in vehicle-treated rats, n = 7, P < 0.05), and decreased cardiac rate with no sustained change in blood pressure. Intraperitoneal 6HDA, 100 mg/kg, as a single dose at 1800, increased plasma leptin approximately twofold after 18-20 h, increased IBAT (but not epididymal fat) leptin mRNA by two- to threefold, and decreased IBAT UCP-3 mRNA to 30-40% of control. Neither AMPT-ME nor 6HDA significantly altered mRNA encoding gastrocnemius muscle UCP-3, IBAT UCP-1, or IBAT and epididymal UCP-2. In summary, AMPT-ME and 6HDA increased plasma leptin and upregulated leptin mRNA expression. AMPT-ME also resulted in complex tissue and subtype-specific modulation of adipose UCP mRNA. These data are consistent with interaction between leptin and sympathetic nerve activity (SNA) in regulation of fat cell energy utilization. However, the in vivo modulation of leptin and UCPs appears complex and, beyond a causal effect of SNA per se, may depend on concurrent changes in plasma insulin, glucose, and circulatory hemodynamics.
Age-related changes of the spinal cord: A biomechanical study

Although it is known that aging plays an important role in the incidence and progression of cervical spondylotic myelopathy (CSM), the underlying mechanism is unclear. Studies that used fresh bovine cervical spinal cord report the gray matter of the cervical spinal cord as being more rigid and fragile than the white matter. However, there are no reports regarding the association between aging an tensile and Finite Element Method (FEM). Therefore, FEM was used based on the data pertaining to the mechanical features of older bovine cervical spinal cord to explain the pathogenesis of CSM in elderly patients. Tensile tests were conducted for white and gray matter separately in young and old bovine cervical spinal cords, and compared with their respective mechanical features. Based on the data obtained, FEM analysis was further performed, which included static and dynamic factors to describe the internal stress distribution changes of the spinal cord. These results demonstrated that the mechanical strength of young bovine spinal cords is different from that of old bovine spinal cords. The gray matter of the older spinal cord was significantly softer and more resistant to rupture compared with that of younger spinal cords (P<0.05). Among the old, although the gray matter was more fragile than the white matter, it was similar to the white matter in terms of its rigidity (P<0.05). The in vitro data were subjected to three compression patterns. The FEM analysis demonstrated that the stress level rises higher in the old spinal cords in response to similar compression, when compared with young spinal cords. These results demonstrate that in analyzing the response of the spinal cord to compression, the age of patients is an important factor to be considered, in addition to the degree of compression, compression speed and parts of the spinal cord compression factor.
From good institutions to generous citizens: Top-down incentives to cooperate promote subsequent prosociality but not norm enforcement

What makes people willing to pay costs to help others, and to punish others' selfishness? Why does the extent of such behaviors vary markedly across cultures? To shed light on these questions, we explore the role of formal institutions in shaping individuals' prosociality and punishment. In Study 1 (N=707), American participants who reported living under higher quality cooperation-enforcing institutions (police and courts) gave significantly more in a Dictator Game (DG), but did not punish significantly more in a Third-Party Punishment Game (TPPG). In Study 1R (N=1705), we replicated the positive relationship between reported institutional quality and DG giving observed in Study 1. In Study 2 (N=516), we experimentally manipulated institutional quality in a repeated Public Goods Game with a centralized punishment institution. Consistent with the correlational results of Study 1 and 1R, we found that centralized punishment led to significantly more prosociality in a subsequent DG compared to a no-punishment control, but had no significant direct effect on subsequent TPPG punishment (only an indirect effect via increased DG giving). Thus we present convergent evidence that the quality of institutions one is exposed to "spills over" to subsequent prosociality but not punishment. These findings support a theory of social heuristics, suggest boundary conditions on spillover effects of cooperation, and demonstrate the power of effective institutions for instilling habits of virtue and creating cultures of cooperation.
New Results on H8 Control of Input Delay Systems

The problem of delay-dependent Hinfin control for systems with state and input delays is considered in this paper. By using the idea of delay fractioning, an improved Hinfin performance criterion is proposed. Moreover, based on this criterion, a new procedure for designing delay-dependent Hinfin state feedback controllers is obtained, which ensures that the closed-loop system is asymptotically stable with an Hinfin disturbance attenuation level gamma. These results are shown, via extensive numerical examples, to be much less conservative than most of the existing ones in the literature.
Syddansk Universitet Association Between Portosystemic Shunts and Increased Complications and Mortality in Patients With Cirrhosis

Simón-Talero, Macarena; Roccarina, Davide; Martínez, Javier; Lampichler, Katharina; Baiges, Anna; Low, Gavin; Llop, Elba; Praktiknjo, Michael; Maurer, Martin H; Zipprich, Alexander; Triolo, Michela; Vangrinsven, Guillaume; Garcia-Martinez, Rita; Dam Fialla, Annette; Majumdar, Avik; Picón, Carmen; Toth, Daniel; Darnell, Anna; Abraldes, Juan G; Lopez, Marta; Kukuk, Guido; Krag, Aleksander; Bañares, Rafael; Laleman, Wim; La Mura, Vincenzo; Ripoll, Cristina; Berzigotti, Annalisa; Trebicka, Jonel; Calleja, Jose Luis; Tandon, Puneeta; Hernandez-Gea, Virginia; Reiberger, Thomas; Albillos, Agustín; Tsochatzis, Emmanuel A; Augustin, Salvador; Genescà, Joan; Quiroga, Sergi; Yu, Dominic; Mandorfer, Mattias; Garcia-Pagan, Juan Carlos; Berbel, Claudia; Ferrusquia, Jose; Ble, Michel; GarciaCriado, Mari Angeles; Belmonte, Ernest; Ney, Michael; Margini, Cristina; Casu, Stefania; Murgia, Giuseppe; Ludwig, Christiane; Baveno VI-SPSS group from the Baveno Cooperation, Baveno VI-SPSS group
Structure detection in the D1 CFHTLS deep field using accurate photometric redshifts: a benchmark

We investigate structures in the D1 CFHTLS deep field in order to test the method that will be applied to generate homogeneous samples of clusters and groups of galaxies in order to constrain cosmology and detailed physics of groups and clusters. Adaptive kernel technique is applied on galaxy catalogues. This technique needs none of the usual a-priori assumptions (luminosity function, density profile, colour of galaxies) made with other methods. Its main drawback (decrease of efficiency with increasing background) is overcame by the use of narrow slices in photometric redshift space. There are two main concerns in structure detection. One is false detection and the second, the evaluation of the selection function in particular if one wants "complete" samples. We deal here with the first concern using random distributions. For the second, comparison with detailed simulations is foreseen but we use here a pragmatic approach with comparing our results to GalICS simulations to check that our detection number is not totally at odds compared to cosmological simulations. We use XMM-LSS survey and secured VVDS redshifts up to z~1 to check individual detections. We show that our detection method is basically capable to recover (in the regions in common) 100% of the C1 XMM-LSS X-ray detections in the correct redshift range plus several other candidates. Moreover when spectroscopic data are available, we confirm our detections, even those without X-ray data.