Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery

A bioinspired approach was developed for STING agonist delivery with STINGΔTM as a functional carrier. The stimulator of interferon (IFN) genes (STING) pathway constitutes a highly important part of immune responses against various cancers and infections. Consequently, administration of STING agonists such as cyclic GMP-AMP (cGAMP) has been identified as a promising approach to target these diseases. In cancer cells, STING signaling is frequently impaired by epigenetic silencing of STING; hence, conventional delivery of only its agonist cGAMP may be insufficient to trigger STING signaling. In this work, while expression of STING lacking the transmembrane (TM) domain is known to be unresponsive to STING agonists and is dominant negative when coexpressed with the full-length STING inside cells, we observed that the recombinant TM-deficient STING protein complexed with cGAMP could effectively trigger STING signaling when delivered in vitro and in vivo, including in STING-deficient cell lines. Thus, this bioinspired method using TM-deficient STING may present a universally applicable platform for cGAMP delivery.
Trends in Research and Graduate Programs in Schools and Colleges of Pharmacy, Part 1: Programs

Objective. To examine the landscape of research and graduate education nationally and within schools and colleges of pharmacy. This report is part 1 of a three-part series and focuses on graduate programs’ research funding and science faculty composition and diversity. Findings. Between FY2008 and FY2017, the number of full-time faculty members in schools and colleges of pharmacy increased 36%. The number of pharmacy schools with National Institutes of Health (NIH) awards increased by 15%, while NIH grants per faculty principal investigator (PI) increased by 31%. However, unadjusted for inflation, the mean NIH dollar amount per-faculty member PI increased just 14% and the mean NIH dollar amount per-school declined 7%, indicating that number of funded faculty outpaced dollars available. Proportionately, the percentage of science faculty members at pharmacy schools decreased from 47% to 43%. Only 15 public, research-intensive schools and colleges of pharmacy received more than half of the combined FY2017 NIH funding and total funding, while all other public and private schools and colleges of pharmacy shared the remaining funds. Interdisciplinary programs are developing slowly, and may help to diversify and increase future funding. Proportions of tenured and tenure-track positions are declining, but biological sciences and social and administrative sciences disciplines are growing and women faculty are making significant gains in these fields and at the assistant professor rank. Summary. Research-intensive schools and colleges of pharmacy are best-positioned to lead the academy to reframe graduate education to build interdisciplinary team skills and attract more diverse funding and science faculty members.
The impact of human activity on the aquatic macroflora of Llangorse Lake, South Wales

1. The first recorded effects of human activity on the aquatic flora of Llangorse Lake, South Wales, were the result of introductions of Elodea canadensis in the early 1900s and of Nymphoides peltata in 1936, altering the species balance of both submerged and floating plant communities. 2. The most significant impact on the lake in recent times has been effluent from the sewage treatment works, which discharged into the lake between the early 1950s and 1982, and the impact of a concurrent intensification of agriculture within the catchment, both leading to accelerated eutrophication. 3. The eutrophication of the lake resulted in a significant change in the submerged flora, which declined in diversity and extent to only a few stands of two species in 1982. 4. Following the diversion of the sewage effluent, the submerged flora recovered to a situation similar to that existing before the effects of accelerated eutrophication. 5. The emergent and floating plant communities did not reflect the eutrophication in the same way as the submerged flora, although Equisetum fluviatile has declined noticeably. 6. The floating and emergent communities, notably Phragmites australis reed swamp, have been significantly damaged in the immediate vicinity of mooring developments, but elsewhere the introduction of water-based recreation cannot be demonstrated to have had a widespread detrimental effect. 7. The recovery of the submerged plant community is considered to be in part due to residual populations of the various species ‘lost’ from the main body of the lake existing in refugia in and around the lake. 8. The history of the lake is notable in terms of the recovery of the submerged flora and in the absence of dominants new to the system invading during the period of accelerated eutrophication. Copyright © 1999 John Wiley & Sons, Ltd.
Negative dominance and dominance-by-dominance epistatic effects reduce grain-yield heterosis in wide crosses in wheat

Breeding exploits the phenomenon of heterosis for an improved productivity, but negative effects reduce heterosis in wide crosses. The genetics underlying heterosis, the difference in performance of crosses compared with midparents, is hypothesized to vary with relatedness between parents. We established a unique germplasm comprising three hybrid wheat sets differing in the degree of divergence between parents and devised a genetic distance measure giving weight to heterotic loci. Heterosis increased steadily with heterotic genetic distance for all 1903 hybrids. Midparent heterosis, however, was significantly lower in the hybrids including crosses between elite and exotic lines than in crosses among elite lines. The analysis of the genetic architecture of heterosis revealed this to be caused by a higher portion of negative dominance and dominance-by-dominance epistatic effects. Collectively, these results expand our understanding of heterosis in crops, an important pillar toward global food security.
Differences in Ca2+-management between the ventricle of two species of neotropical teleosts: the jeju, Hoplerythrinus unitaeniatus (Spix & Agassiz, 1829), and the acara, Geophagus brasiliensis (Quoy & Gaimard, 1824)

This study analyzed the physiological role of the cardiac sarcoplasmic reticulum (SR) of two neotropical teleosts, the jeju, Hoplerythrinus unitaeniatus (Erythrinidae), and the acara, Geophagus brasiliensis (Cichlidae). While the in vivo heart frequency (fH - bpm) of acara (79.6 ± 6.6) was higher than that of the jeju (50.3 ± 2.7), the opposite was observed for the ventricular inotropism (Fc - mN/mm2) at 12 bpm (acara = 28.66 ± 1.86 vs. jeju = 36.09 ± 1.67). A 5 min diastolic pause resulted in a strong potentiation of Fc (≅ 90%) of strips from jeju, which was completely abolished by ryanodine. Ryanodine also resulted in a ≅ 20% decrease in the Fc developed by strips from jeju at both subphysiological (12 bpm) and physiological (in vivo) frequencies. However, this effect of ryanodine reducing the Fc from jeju was completely compensated by adrenaline increments (10-9 and 10-6 M). In contrast, strips from acara were irresponsive to ryanodine, irrespective of the stimulation frequency, and increases in adrenaline concentration (to 10-9 and 10-6 M) further increased Fc. These results reinforce the hypothesis of the functionality of the SR as a common trait in neotropical ostariophysian (as jeju), while in acanthopterygians (as acara) it seems to be functional mainly in 'athletic' species.
Bows and arrows and complex symbolic displays 48,000 years ago in the South Asian tropics

Fa-Hien Lena provides evidence for bone-tipped arrows and brilliant symbolic displays 48,000 years ago in tropical Sri Lanka. Archaeologists contend that it was our aptitude for symbolic, technological, and social behaviors that was central to Homo sapiens rapidly expanding across the majority of Earth’s continents during the Late Pleistocene. This expansion included movement into extreme environments and appears to have resulted in the displacement of numerous archaic human populations across the Old World. Tropical rainforests are thought to have been particularly challenging and, until recently, impenetrable by early H. sapiens. Here, we describe evidence for bow-and-arrow hunting toolkits alongside a complex symbolic repertoire from 48,000 years before present at the Sri Lankan site of Fa-Hien Lena—the earliest bow-and-arrow technology outside of Africa. As one of the oldest H. sapiens rainforest sites outside of Africa, this exceptional assemblage provides the first detailed insights into how our species met the extreme adaptive challenges that were encountered in Asia during global expansion.
Evolutionary Dynamics of Stochastic SEIR Models with Migration and Human Awareness in Complex Networks

In this paper, a stochastic SEIR (Susceptible-Exposed-Infected-Removed) epidemic dynamic model with migration and human awareness in complex networks is constructed. The awareness is described by an exponential function. The existence of global positive solutions for the stochastic system in complex networks is obtained. The sufficient conditions are presented for the extinction and persistence of the disease. Under the conditions of disease persistence, the distance between the stochastic solution and the local disease equilibrium of the corresponding deterministic system is estimated in the time sense. Some numerical experiments are also presented to illustrate the theoretical results. Although the awareness introduced in the model cannot affect the extinction of the disease, the scale of the disease will eventually decrease as human awareness increases.
Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real‐life study

Fifteen percent of patients with myasthenia gravis (MG) are refractory to conventional treatment. Case reports and a few studies show probable benefit of rituximab in these cases. Our objective was to assess the efficacy and the safety of rituximab in patients with MG, in a multicentric real‐life study.
RANK and RANKL Expression in Salivary Gland Tumors

Objectives: The pathogenesis and molecular basis of salivary gland tumors (SGT) are not well understood. We investigated the expression of receptor activator of nuclear factor κB (RANK) and RANK ligand (RANKL) in benign and malignant SGTs and their relationship with clinicopathological features. Methods: Fifty malignant and 38 benign SGTs were analyzed in this study. We evaluated the correlation between RANK and RANKL expression and benign and malignant tumors, as well as the correlation between clinicopathological prognostic parameters and RANK and RANKL expression. Results: Receptor activator of nuclear factor κB was positive in 82% (41) malignant SGTs and in 34.2% (13) benign SGTs. Receptor activator of nuclear factor κB ligand was expressed in 28% (14) malignant and 5.3% (2) benign tumors. Receptor activator of nuclear factor κB and RANKL expression were significantly different between benign and malignant SGTs (P < .001, P = .006, respectively). However, a relationship was not found between positive expression of RANK or RANKL and clinicopathological features. Conclusions: In our study, RANK and RANKL expression was found to be higher in malignant SGTs compared to benign SGTs and RANK was more sensitive than RANKL. In addition, RANK and RANKL expression was higher in some malignant histological subtypes. Based on these results, we think that RANK and RANKL expression in SGTs and its potential as a target for treatment should continue to be investigated.
Simulating the effect of flowering time on maize individual leaf area in contrasting environmental scenarios

Abstract The quality of yield prediction is linked to that of leaf area. We first analysed the consequences of flowering time and environmental conditions on the area of individual leaves in 127 genotypes presenting contrasting flowering times in fields of Europe, Mexico, and Kenya. Flowering time was the strongest determinant of leaf area. Combined with a detailed field experiment, this experiment showed a large effect of flowering time on the final leaf number and on the distribution of leaf growth rate and growth duration along leaf ranks, in terms of both length and width. Equations with a limited number of genetic parameters predicted the beginning, end, and maximum growth rate (length and width) for each leaf rank. The genotype-specific environmental effects were analysed with datasets in phenotyping platforms that assessed the effects (i) of the amount of intercepted light on leaf width, and (ii) of temperature, evaporative demand, and soil water potential on leaf elongation rate. The resulting model was successfully tested for 31 hybrids in 15 European and Mexican fields. It potentially allows prediction of the vertical distribution of leaf area of a large number of genotypes in contrasting field conditions, based on phenomics and on sensor networks.
Performance analyses and code transformations for MATLAB applications. (Analyses de performances et transformations de code pour les applications MATLAB)

MATLAB est un environnement informatique dote d'un langage de programmation simple et d'une vaste bibliotheque de fonctions couramment utilisees en science et ingenierie (CSE) pour le prototypage rapide. Cependant, certaines caracteristiques de son environnement, comme son langage dynamique ou son style de programmation interactif, affectent la rapidite d'execution des programmes. Les approches actuelles d'amelioration des programmes MATLAB traduisent le code dans des langages statiques plus rapides comme C ou Fortran, ou bien appliquent systematiquement des transformations de code au programme MATLAB sans considerer leur impact sur les performances. Dans cette these, nous comblons cette lacune en developpant des techniques d'analyse et de transformation de code des programmes MATLAB afin d'augmenter leur performance. Plus precisement, nous analysons et modelisons le comportement d'un environnement MATLAB black-box uniquement en mesurant l'execution caracteristique des programmes sur CPU. A partir des donnees obtenues, nous formalisons un modele statique qui predit le type et l'ordonnancement des instructions programmees lors de l'execution par le compilateur Just-In-Time (JIT). Ce modele nous permet de proposer plusieurs transformations de code qui ameliorent les performances des programmes MATLAB en influencant la facon dont le compilateur JIT genere le code machine. Les resultats obtenus demontrent les avantages pratiques de la methodologie presentee.
Unrecognized ROPER in a child with a novel pathogenic variant in ZNF408 gene

ABSTRACT Background Familial exudative vitreoretinopathy (FEVR) is a rare hereditary disorder characterized by abnormal or incomplete retinal angiogenesis commonly inherited in an autosomal dominant fashion. Up to 50% of FEVR cases are linked to known genetic mutations affecting retinal vasculature development. Purpose To report a case, a novel pathogenic variant of the ZNF408 gene associated with a case of FEVR in a premature male. Materials and methods Case report Results A 10-month-old male who was born prematurely at 34 weeks’ gestation in the Dominican Republic was referred for persistent avascular retina. The baby was treated with bilateral intravitreal ranibizumab injections for retinopathy of prematurity (ROP) with the presence of plus disease. Fundus examination several months after treatment revealed the absence of tortuosity of the vessels with avascular periphery; fluorescein angiography (FA) confirmed peripheral avascularity and demonstrated irregular sprouts of vascularization in the absence of neovascularization. We performed genetic testing under the suspicion of FEVR and results identified a heterozygous mutation in the ZNF408 gene on chromosome 11, c.1307 C > T. Conclusion FEVR is an important differential diagnosis in premature infants with retinopathy, as clinical presentation can overlap with common findings in ROP. Maintaining high suspicion for the disease is especially critical in cases with findings unusual for ROP. FEVR in the presence of prematurity has been well described, falling under the proposed term ROPER. Genetic testing is key to confirm diagnosis.
Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

Intrauterine growth retardation (IUGR), which induces epigenetic modifications and permanent changes in gene expression, has been associated with the development of type 2 diabetes. Using a rat model of IUGR, we performed ChIP-Seq to identify and map genome-wide histone modifications and gene dysregulation in islets from 2- and 10-week rats. IUGR induced significant changes in the enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in both 2-wk and 10-wk islets, which were correlated with expression changes of multiple genes critical for islet function in IUGR islets. ChIP-Seq analysis showed that IUGR-induced histone mark changes were enriched at critical transcription factor binding motifs, such as C/EBPs, Ets1, Bcl6, Thrb, Ebf1, Sox9, and Mitf. These transcription factors were also identified as top upstream regulators in our previously published transcriptome study. In addition, our ChIP-seq data revealed more than 1000 potential bivalent genes as identified by enrichment of both H3K4me3 and H3K27me3. The poised state of many potential bivalent genes was altered by IUGR, particularly Acod1, Fgf21, Serpina11, Cdh16, Lrrc27, and Lrrc66, key islet genes. Collectively, our findings suggest alterations of histone modification in key transcription factors and genes that may contribute to long-term gene dysregulation and an abnormal islet phenotype in IUGR rats.
Resequencing of the Red Alga Cyanidioschyzon merolae: Strain Differences and Mitochondrial Sequence Corrections

Two laboratory strains of the red alga Cyanidioschyzon merolae 10D were resequenced. We found some strain differences in the nuclear and chloroplast genomes. We also identified corrections of the mitochondrial genome sequence. ABSTRACT Two laboratory strains of the red alga Cyanidioschyzon merolae 10D were resequenced. We found some strain differences in the nuclear and chloroplast genomes. We also identified corrections of the mitochondrial genome sequence.
Respiration rates predict differences in growth of coast redwood

The relation between growth rate traits (height, basal diameter, stem volume and branch diameter) and two measures of respiration rate [metabolic heat rate (q) and CO2 production rate (Rco2)] and their ratio (q/Rco2) was examined on a collection of 192 different genotypes of coast redwoods [Sequoia sempervirens (D.Don) Endl. ]. Branch diameter was not correlated with any of the respiratory measures, but the other three growth traits gave highly significant (P < 0.001) correlations with positive slopes. Combining the four growth traits and the three respiratory variables (q, RCo2 and q/Rco2) to give two canonical variates, one representing growth and one representing respiration, gives an even stronger linear correlation (r= 0–85). These data suggest that simultaneous assay of multiple respiratory measures on juvenile trees can be used to predict their longer-term growth rates.
LSDBs: Promise and Challenges

Locus-specific databases (LSDBs) provide information about causative mutations and phenotypic patterns associated with a specific mutation, enabling researchers to define an optimal strategy for mutation detection. LSDBs exist for hundreds of disease-related genes. Researchers have also been creating a number of national LSDBs for disease genes and different populations, such as the Greek, Israeli, and Egyptian. Building from the experience they developed in the last decade from creating many LSDBs, Mitropoulou et al. (Hum Mutat 31:1109– 1116, 2010) now compare the performance of 1,188 LSDBs by analyzing them for the presence or absence of 44 content criteria related to database features. They concluded that today there is less data-content heterogeneity than existed eight years ago, when a similar analysis was performed by Claustres and al. (Genome Res 12:680– 688, 2002). This is good news. But just how useful are LSDBs for helping clinical genetic services in making a diagnosis? The answer from Mitropoulou et al. is not encouraging: ‘‘current LSDBs do not support data retrieval and transmission between scientific personnel and clinicians working in diagnostic laboratories. ’’ Their analysis pinpoints a number of deficiencies, namely lack of detailed disease and phenotypic descriptions for each genetic variant that, if addressed, would allow LSDBs to better serve the clinical genetics community, and not just researchers. They propose the concept of clinical genetics databases (CGDBs) and the development of a federation of LSDBs and CGDBs that would bridge the divide between gene-centric and genome-wide approaches to databasing variation. This type of work should be promoted and encouraged first and foremost at the national level. The Israeli NEMDB (http:// www.goldenhelix.org/server/israeli/) provides a good example for other national LSDBs in providing useful information to genetic services for any country. On the other hand, the integration of mutation analysis tools proposed by Mitropoulou et al. might become one of the main goals of new international projects aiming at collaborative genomics for human health, as recently proposed, for example, for the Mediterranean region by Ozcelik et al. (Nature Genet 42:641– 645, 2010).
Natural temperature regimes for loggerhead and green turtle nests in the eastern Mediterranean

Temperatures of green turtle (Chelonia mydas) and loggerhead turtle (Caretta caretta) nests on the beaches of northern Cyprus and Turkey were examined. Electronic continuous-temperature recorders programmed by computer were placed at the top, middle, and bottom of the nests. The sex of 3-7 hatchlings from each level was determined from gonadal histology. The maximum temperature increase during the incubation period was 9.6oC for both species. The mean temperature during the middle third of the incubation period is a good indicator of the sex ratio of the clutch. The percentage of female embryos increased with temperature, 50% being female at 29°C. The mean temperature over the entire incubation period is not a good indicator of sex ratio but can be used to predict the duration of incubation period. The temperature differences within the clutch were larger in loggerhead than in green turtle nests. Eggs at the top of the nest experienced generally warmer (up to 1.4°C) conditions than eggs at the bottom of t.
Sprouting, succession and tree species diversity in a South African coastal dune forest

Abstract: Sprouting may play a significant role in maintenance of plant diversity where prevailing disturbance frequency and severity allows. When disturbance frequency and severity decrease, strong sprouters may be outcompeted. As a result, species composition and diversity may change. This study was carried out to investigate the relationship between sprouting, succession and species diversity in a coastal dune forest that currently suffers from low-severity, chronic disturbance due to sea winds and loose sand substrate. Historically, the site was occupied by shifting cultivators who left the site about 80 y ago. Data on trees that were at least 1.3 m tall from 42 sample plots measuring 20 × 20 m were used. The plots were ranked in order of advancement of succession using the first axis of Principal Components Analysis of forest structural variables. Regeneration pattern was examined using analysis of stem diameter frequency distribution. Abundance and regeneration of strong basal sprouters, incidence of basal sprouting and species diversity decreased with advancement of succession. Only a few species could regenerate under the canopy of late-successional sites. Basal sprouts decreased with advancement of succession whereas trunk sprouts increased. These results suggest that maintenance of high species diversity may need a level of disturbance that allows regeneration and maintenance of strong basal sprouters.