Miracle-dz/UniFAR-FTUs huggingface dataset:
The Salt-Stress Response of the Transgenic Plum Line J8-1 and Its Interaction with the Salicylic Acid Biosynthetic Pathway from Mandelonitrile

Salinity is considered as one of the most important abiotic challenges that affect crop productivity. Plant hormones, including salicylic acid (SA), are key factors in the defence signalling output triggered during plant responses against environmental stresses. We have previously reported in peach a new SA biosynthetic pathway from mandelonitrile (MD), the molecule at the hub of the cyanogenic glucoside turnover in Prunus sp. In this work, we have studied whether this new SA biosynthetic pathway is also present in plum and the possible role this pathway plays in plant plasticity under salinity, focusing on the transgenic plum line J8-1, which displays stress tolerance via an enhanced antioxidant capacity. The SA biosynthesis from MD in non-transgenic and J8-1 micropropagated plum shoots was studied by metabolomics. Then the response of J8-1 to salt stress in presence of MD or Phe (MD precursor) was assayed by measuring: chlorophyll content and fluorescence parameters, stress related hormones, levels of non-enzymatic antioxidants, the expression of two genes coding redox-related proteins, and the content of soluble nutrients. The results from in vitro assays suggest that the SA synthesis from the MD pathway demonstrated in peach is not clearly present in plum, at least under the tested conditions. Nevertheless, in J8-1 NaCl-stressed seedlings, an increase in SA was recorded as a result of the MD treatment, suggesting that MD could be involved in the SA biosynthesis under NaCl stress conditions in plum plants. We have also shown that the plum line J8-1 was tolerant to NaCl under greenhouse conditions, and this response was quite similar in MD-treated plants. Nevertheless, the MD treatment produced an increase in SA, jasmonic acid (JA) and reduced ascorbate (ASC) contents, as well as in the coefficient of non-photochemical quenching (qN) and the gene expression of Non-Expressor of Pathogenesis-Related 1 (NPR1) and thioredoxin H (TrxH) under salinity conditions. This response suggested a crosstalk between different signalling pathways (NPR1/Trx and SA/JA) leading to salinity tolerance in the transgenic plum line J8-1.
Nano-Mediated Photodynamic Therapy for Cancer: Enhancement of Cancer Specificity and Therapeutic Effects

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and obtain better treatment options for cancer, novel modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer, and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are very capable of penetrating the cancer stem cell niche, simultaneously killing cancer cells and eradicating drug-resistant cancer stem cells, yielding therapeutic efficiency of up to 100-fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.
Identification of a variant associated with early‐onset diabetes in the intron of the insulin gene with exome sequencing

Whole‐exome sequencing is a new technology. We used it to explore the gene responsible for early‐onset diabetes as a result of impaired insulin secretion in a family. In the INS gene, we identified the heterozygous c.188‐31G>A mutation in the proband – a 43‐year‐old woman. The mutation was also identified in her two daughters with diabetes, but not in her son or her parents, all of whom did not have diabetes. The substitution was located 31 bp proximal to exon 3 in intron 2. It was predicted to create an ectopic splice site leading to inserting 29 nucleotides of intron 2 as an exonic sequence in the transcript. The mutation has been reported in White families, and the present case is the first report in an Asian person. The present results would help in understanding the role of the mutation in developing diabetes.
Advances in understanding the role of angiotensin-regulated proteins in kidney diseases

ABSTRACT Introduction: Renin–angiotensin system (RAS) blockers are in clinical use to treat high blood pressure and proteinuric chronic kidney disease. However, RAS blockade is limited by the risk of hyperkalemia, angiotensin receptor blockers are not clinically superior to angiotensin-converting enzyme inhibitors and dual RAS blockade is formally contraindicated. Areas covered: We review the regulation of protein expression and activation by angiotensin II and RAS blockers as it contributes to kidney disease. Specifically excluded are direct renin actions as well as aldosterone actions. The search strategy included the terms angiotensin, protein, proteomics, inflammation, fibrosis, and kidney and was complemented by additional searches based on initial results. Expert commentary: Recent developments include an improved understanding of the structure, function, and signaling of angiotensin G-protein-coupled receptors; identification of ligands that behave as agonists, antagonists, and even reverse agonists on specific signaling and functional pathways of the same receptor; characterization of further signaling pathways by applying proteomics and phosphoproteomics; and systems biology approaches to characterize signatures of adequate RAS blockade or resistance of kidney injury to RAS blockade. These developments will allow optimization of clinical RAS targeting to improve kidney outcomes through precision nephrology strategies that may include combined approaches, along the path marked by clinically successful dual RAS/neprilysin blockade.
An updated view on the origin and use of angiogenic biomarkers for preeclampsia

ABSTRACT Introduction: The last decade has seen massive efforts towards the identification and the potential use of predictive biomarkers for the pregnancy pathology preeclampsia. The angiogenic factors sFlt-1 and placental growth factor (PGF) have been in focus and have been massively supported. Areas covered: This review describes preeclampsia and intra-uterine growth restriction (IUGR), focusing on sFlt-1 and PGF, their sources during and outside pregnancy and the application of these markers in diseases outside pregnancy. Finally, the specificity of the angiogenic markers for preeclampsia is discussed. Expert commentary: The admixture of the two independent syndromes preeclampsia and IUGR has not helped in identifying the etiologies of either. Rather, it has made the search for new markers and pathways much more complicated as has the constriction on the angiogenic markers. The current markers sFlt-1 and PGF have a clear value once an adverse outcome is diagnosed but are not specific for preeclampsia. Also, they are mostly derived from the maternal vascular system rather than the placenta and are already in use as markers outside pregnancy. A new holistic approach using disease maps and interoperable workflows based on topic-related big data will help in broadening our understanding of the etiology of preeclampsia and hence, develop new markers and therapies.
Characterization of Comorbidities Limiting the Recruitment of Patients in Early Phase Clinical Trials.

BACKGROUND Early phase clinical trials evaluate the safety and efficacy of new treatments. The exclusion/inclusion criteria in these trials are usually rigorous and may exclude many patients seen in clinical practice. Our objective was to study the comorbidities limiting the participation of patients with breast, colorectal, or lung cancer in clinical trials. MATERIALS AND METHODS We queried ClinicalTrials.gov on December 31, 2016. We reviewed the eligibility criteria of 1,103 trials. Logistic regression analyses were completed, and exclusion was studied as a binary variable. RESULTS Out of 1,103 trials, 70 trials (6%) excluded patients >75 years of age, and 45% made no reference to age. Eighty-six percent of trials placed restrictions on patients with history of prior malignancies. Regarding central nervous system (CNS) metastasis, 416 trials (38%) excluded all patients with CNS metastasis, and 373 (34%) only allowed asymptomatic CNS metastasis. Regarding chronic viral infections, 347 trials (31%) excluded all patients with human immunodeficiency virus, and 228 trials (21%) excluded all patients with hepatitis B or C infection. On univariate analysis, chemotherapy trials were more likely to exclude patients with CNS metastasis and history of other malignancies than targeted therapy trials. Multivariate analysis demonstrated that industry-sponsored trials had higher odds of excluding patients with compromised liver function. CONCLUSION Many clinical trials excluded large segments of the population of patients with cancer. Frequent exclusion criteria included patients with CNS metastasis, history of prior malignancies, and chronic viral infections. The criteria for participation in some clinical trials may be overly restrictive and limit enrollment. IMPLICATIONS FOR PRACTICE The results of this study revealed that most early phase clinic trials contain strict exclusion criteria, potentially excluding the patients who may be more likely to represent the population treated in clinical settings, leaving patients susceptible to unintended harm from inappropriate generalization of trial results. Careful liberalization of the inclusion/exclusion criteria in clinical trials will allow investigators to understand the benefits and drawbacks of the experimental drug for a broader population, and possibly improve recruitment of patients with cancer into clinical trials.
Single Molecule FRET: A Powerful Tool to Study Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) are often modeled using ideas from polymer physics that suggest they smoothly explore all corners of configuration space. Experimental verification of this random, dynamic behavior is difficult as random fluctuations of IDPs cannot be synchronized across an ensemble. Single molecule fluorescence (or Förster) resonance energy transfer (smFRET) is one of the few approaches that are sensitive to transient populations of sub-states within molecular ensembles. In some implementations, smFRET has sufficient time resolution to resolve transitions in IDP behaviors. Here we present experimental issues to consider when applying smFRET to study IDP configuration. We illustrate the power of applying smFRET to IDPs by discussing two cases in the literature of protein systems for which smFRET has successfully reported phosphorylation-induced modification (but not elimination) of the disordered properties that have been connected to impacts on the related biological function. The examples we discuss, PAGE4 and a disordered segment of the GluN2B subunit of the NMDA receptor, illustrate the great potential of smFRET to inform how IDP function can be regulated by controlling the detailed ensemble of disordered states within biological networks.
Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity

Beyond anticoagulation, the therapeutic potential of heparin derivatives and heparan sulfate (HS) mimetics (functionally defined HS mimetics) in oncology is related to their ability to bind and modulate the function of a vast array of HS-binding proteins with pivotal roles in cancer growth and progression. The definition of structural/functional determinants and the introduction of chemical modifications enabled heparin derivatives to be identified with greatly reduced or absent anticoagulant activity, but conserved/enhanced anticancer activity. These studies paved the way for the disclosure of structural requirements for the inhibitory effects of HS mimetics on heparanase, selectins, and growth factor receptor signaling, as well as for the limitation of side effects. Actually, HS mimetics affect the tumor biological behavior via a multi-target mechanism of action based on their effects on tumor cells and various components of the tumor microenvironment. Emerging evidence indicates that immunomodulation can participate in the antitumor activity of these agents. Significant ability to enhance the antitumor effects of combination treatments with standard therapies was shown in several tumor models. While the first HS mimetics are undergoing early clinical evaluation, an improved understanding of the molecular contexts favoring the antitumor action in certain malignancies or subgroups is needed to fully exploit their potential.
Exergaming for Children and Adolescents: Strengths, Weaknesses, Opportunities and Threats

Exergaming, or active video gaming, has become an emerging trend in fitness, education and health sectors. It is defined as digital games that require bodily movements to play, stimulating an active gaming experience to function as a form of physical activity (PA). Since exergaming is becoming more popular, claims have been made on the usefulness of exergaming. It has, for example, been entitled as being “the future of fitness” by the American College of Sports Medicine, promoting PA and health in children and adolescents. However, research also suggests that long-term engagement in exergaming is difficult to achieve, and there is a noticeable reservation towards exergaming by parents, teachers and caregivers. To provide an overview and to outline the future directions of exergaming, the aim of this review was to critically illustrate the strengths, weaknesses, opportunities and threats of exergaming to promote PA and health in children and youth. The available evidence indicates that exergaming has the potential to improve health via an increase in PA. However, it seems that this potential is frequently underexploited, and further developments such as customized exergames are needed.
Bioactive Natural Spirolactone-Type 6,7-seco-ent-Kaurane Diterpenoids and Synthetic Derivatives

Diterpenoids are widely distributed natural products and have caused considerable interest because of their unique skeletons and antibacterial and antitumor activities and so on. In light of recent discoveries, ent-kaurane diterpenoids, which exhibit a wide variety of biological activities, such as anticancer and anti-inflammatory activities, pose enormous potential to serve as a promising candidate for drug development. Among them, spirolactone-type 6,7-seco-ent-kaurane diterpenoids, with interesting molecular skeleton, complex oxidation patterns, and bond formation, exhibit attractive activities. Furthermore, spirolactone-type diterpenoids have many modifiable sites, which allows for linking to various substituents, suitable for further medicinal study. Hence, some structurally modified derivatives with improved cytotoxicity activities are also achieved. In this review, natural bioactive spirolactone-type diterpenoids and their synthetic derivatives were summarized.
Residual vision activation and the brain-eye-vascular triad: Dysregulation, plasticity and restoration in low vision and blindness – a review

Vision loss due to ocular diseases such as glaucoma, optic neuropathy, macular degeneration, or diabetic retinopathy, are generally considered an exclusive affair of the retina and/or optic nerve. However, the brain, through multiple indirect influences, has also a major impact on functional visual impairment. Such indirect influences include intracerebral pressure, eye movements, top-down modulation (attention, cognition), and emotionally triggered stress hormone release affecting blood vessel dysregulation. Therefore, vision loss should be viewed as the result of multiple interactions within a “brain-eye-vascular triad”, and several eye diseases may also be considered as brain diseases in disguise. While the brain is part of the problem, it can also be part of the solution. Neuronal networks of the brain can “amplify” residual vision through neuroplasticity changes of local and global functional connectivity by activating, modulating and strengthening residual visual signals. The activation of residual vision can be achieved by different means such as vision restoration training, non-invasive brain stimulation, or blood flow enhancing medications. Modulating brain functional networks and improving vascular regulation may offer new opportunities to recover or restore low vision by increasing visual field size, visual acuity and overall functional vision. Hence, neuroscience offers new insights to better understand vision loss, and modulating brain and vascular function is a promising source for new opportunities to activate residual vision to achieve restoration and recovery to improve quality of live in patients suffering from low vision.
The role of time in information processing: a survey

Numerous researchers in a handful of disciplines have been concerned, in recent years, with the special role (or roles) that time seems to play in information processing. Designers of computerized information systems have had to deal with the fact that when an information item becomes outdated, it need not be forgotten. Researchers in artificial intelligence have pointed to the need for a realistic world model to include representations not only for snapshot descriptions of the real world, but also for histories, or the evolution of such descriptions over time. Many logicians have regarded classical logic as an awkward tool for capturing the relationships and the meaning of statements involving temporal reference, and have proposed special "temporal logics" for this purpose. Finally, the analysis of tensed statements in natural language is a principal concern of researchers in linguistics.
Streaming MASSIF: Cascading Reasoning for Efficient Processing of IoT Data Streams

In the Internet of Things (IoT), multiple sensors and devices are generating heterogeneous streams of data. To perform meaningful analysis over multiple of these streams, stream processing needs to support expressive reasoning capabilities to infer implicit facts and temporal reasoning to capture temporal dependencies. However, current approaches cannot perform the required reasoning expressivity while detecting time dependencies over high frequency data streams. There is still a mismatch between the complexity of processing and the rate data is produced in volatile domains. Therefore, we introduce Streaming MASSIF, a Cascading Reasoning approach performing expressive reasoning and complex event processing over high velocity streams. Cascading Reasoning is a vision that solves the problem of expressive reasoning over high frequency streams by introducing a hierarchical approach consisting of multiple layers. Each layer minimizes the processed data and increases the complexity of the data processing. Cascading Reasoning is a vision that has not been fully realized. Streaming MASSIF is a layered approach allowing IoT service to subscribe to high-level and temporal dependent concepts in volatile data streams. We show that Streaming MASSIF is able to handle high velocity streams up to hundreds of events per second, in combination with expressive reasoning and complex event processing. Streaming MASSIF realizes the Cascading Reasoning vision and is able to combine high expressive reasoning with high throughput of processing. Furthermore, we formalize semantically how the different layers in our Cascading Reasoning Approach collaborate.
Rapid improvement of reading performance in children with dyslexia by altering the reading strategy: A novel approach to diagnoses and therapy of reading deficiencies

Background: Reading disability is termed “dyslexia” if it is much lower than other cognitive abilities according to the intelligence quotient (IQ). This means that dyslexia is caused by an impairment of abilities other than those which the IQ requires. Therefore, reading performance should improve immediately if these impairments are either eliminated or compensated. Objective: The experiments explore conditions under which these impairments are compensated and dyslexic children's poor reading ability immediately improve. Methods: Experiment 1 examined if reducing the number of letters in pseudowords, prolonging the time interval during which the gaze is directed to pseudowords, reducing the amplitude of saccades and prolonging the time interval that elapsed between the beginning of the presentation of a pseudoword and the beginning of the pronunciation of that word influences childrens’ reading performance. A group of 100 German children (71 boys and 29 girls) aged 8 to 13 years, who suffered from dyslexia according to the Zuerich Reading Test, were divided into a training group (n = 50) and an age-matched control group (n = 50) and tested. Both groups participated in experiment 1. Only the children in the training group participated in experiment 2, in which the children learned a compensatory reading strategy. The age - matched control group did not learn the compensatory reading strategy. In the training group, reading performance was tested before and after having learned the new reading strategy. Results: Conditions were found under which all children were able to read 95% of the pseudowords correctly. After having learned a compensatory reading strategy, a mean 58.9% decrease in words read incorrectly was found after a single training session. The difference between the number of reading mistakes before and after the training session was highly significant (Wicoxon Test: p < 0.00001). The effect size showed that the compensatory reading strategy was highly effective (Hedges g = 1.7). The reading ability of an age-matched dyslexic control group showed no improvement. Conclusions: Dyslexic subjects’ reading performance improves significantly when they learn a new reading strategy.
Minimum cost adaptive synchronization: experiments with the ParaSol system

We present a novel adaptive synchronization algorithm, called the minimum average cost (MAC) algorithm, in the context of the parasol parallel simulation system. ParaSol is a multithreaded system for parallel simulation on shared- and distributed-memory environments, designed to support domain-specific Simulation Object Libraries. The proposed MAC algorithm is based on minimizing the cost of synchronization delay and rollback at a process, whenever its simulation driver must decide whether to either proceed optimistically or to delay processing. In the former case the risk is rollback cost, in the event of a straggler's arrival. In the latter case the risk is unnecessary delay, in the event a latecomer is not a straggler. In addition to the MAC algorithm and an optimal delay computation model, we report on some early experiments comparing the performance of MAC-based adaptive synchronization to optimistic synchronization.