Miracle-dz/UniFAR-FTUs huggingface dataset:
Social, Legal, and Ethical Implications of Cognitive Neuroscience: Neuroethics for Short

For most of its history, cognitive neuroscience has been a branch of basic science. The principal goal of cognitive neuroscience has been to understand the neural bases of mental phenomena. Its occasional forays out of the ivory-tower research laboratory, into the ‘‘real world,’’ have generally been into education or its clinical cousin, rehabilitation. Such work rarely raises social, ethical, or legal concerns. As our science has matured, its potential for broader application has grown. Better theories of mind–brain relations, coupled with increasingly powerful methods for measuring and manipulating brain function, have made possible a much wider range of applications. These applications will undoubtedly have both good and bad consequences for individuals and society. A growing number of neuroscientists and bioethicists, joined by social scientists, engineers, philosophers, and legal scholars, have begun to think about these consequences. The result is a new field, called by many of its participants neuroethics. Some neuroethical issues are already familiar, having
Influence of Weight Reduction and Enhanced Protein Intake on Biomarkers of Inflammation in Older Adults with Obesity

Abstract Both aging and obesity are associated with increased levels of pro-inflammatory metabolites, while weight reduction is associated with improvements in inflammatory status. However, few studies have explored the response of key inflammatory markers to the combined settings of weight reduction in an aging population. There are also few studies that have investigated the potential impact of diet composition on inflammatory marker responses. In the MEASUR-UP trial, we evaluated changes in baseline levels of inflammatory markers with post-study levels for a traditional weight loss control group versus a group with generous, balanced protein intake. In this 6-month randomized controlled trial (RCT), older (≥60 years) adults with obesity (BMI ≥30 kg/m2) and Short Physical Performance Battery (SPPB) score of 4–10 were randomly assigned to either a traditional weight loss regimen, (Control, n = 14) or one with higher protein intake (≥30 g) at each meal (Protein, n = 25). All participants were prescribed a hypo-caloric diet and attended weekly support and education groups and weigh-ins. Protein participants consumed ≥30 g of high-quality protein/meal, including lean and extra lean beef provided to them for two of the three meals per day. Protein intakes were 0.8 and 1.2 g/kg/day for Control and Protein, respectively. Adiponectin, leptin, C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, IL-8, serum amyloid A (SAA), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and glycated serum protein (GSP) levels were measured at 0 and 6-month time points. At the 6-month endpoint, there was significant weight loss and decrease in BMI in both the Control (−4.8 ± 8.2 kg; −2.3 ± 2.4 kg/m2; p = 0.05) and Protein (−8.7 ± 7.4 kg; −2.9 ± 2.3 kg/m2; p < 0.0001) groups. SPPB scores improved in both arms, with a superior functional response in Protein (p < 0.05). Body fat (%) at baseline was positively correlated with leptin, hs-CRP, VCAM-1, ICAM-1, and GSP. Several markers of inflammation responded to the Protein group: leptin (p < 0.001), hs-CRP (p < 0.01), and ICAM-1 (p < 0.01) were decreased and adiponectin increased (p < 0.01). There were no significant changes in any inflammatory markers in the Control arm. In the between group comparison, only adiponectin trended towards a group difference (more improvement in Protein; p < 0.07). Our findings in the MEASUR-UP trial show that a weight loss diet with enhanced protein intake is comparable to an adequate protein diet in terms of weight loss success and that it can lead to improvements in inflammatory status, specifically for adiponectin, leptin, hs-CRP, and ICAM-1. These findings are important given current recommendations for higher protein intakes in older adults and justify the additional study of the inflammatory impact of an enhanced protein diet. (ClinicalTrials.gov identifier: NCT01715753) Trial registration: ClinicalTrials.gov identifier: NCT01715753.
Axin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis in Drosophila

ABSTRACT Self-renewal of intestinal stem cells is controlled by Wingless/Wnt-β catenin signaling in both Drosophila and mammals. As Axin is a rate-limiting factor in Wingless signaling, its regulation is essential. Iduna is an evolutionarily conserved ubiquitin E3 ligase that has been identified as a crucial regulator for degradation of ADP-ribosylated Axin and, thus, of Wnt/β-catenin signaling. However, its physiological significance remains to be demonstrated. Here, we generated loss-of-function mutants of Iduna to investigate its physiological role in Drosophila. Genetic depletion of Iduna causes the accumulation of both Tankyrase and Axin. Increase of Axin protein in enterocytes non-autonomously enhanced stem cell divisions in the Drosophila midgut. Enterocytes secreted Unpaired proteins and thereby stimulated the activity of the JAK-STAT pathway in intestinal stem cells. A decrease in Axin gene expression suppressed the over-proliferation of stem cells and restored their numbers to normal levels in Iduna mutants. These findings suggest that Iduna-mediated regulation of Axin proteolysis is essential for tissue homeostasis in the Drosophila midgut. Summary: Iduna regulates stem cell proliferation and intestinal homeostasis.
Absence of Intraocular Lymphatic Vessels in Uveal Melanomas with Extrascleral Growth

The aim of this study was to investigate the presence of intraocular lymphatic vessels in patients with uveal melanomas and extrascleral extension using a panel of lymphatic markers. The following immunohistochemical markers were analyzed: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), podoplanin (D2-40), prospero-related homeobox gene-1 (Prox-1), pan-endothelial marker cluster of differentiation 31 (CD31), and blood vessel endothelium-specific CD34. Lymphatic vessels were defined as a combination of staining of the following positive markers: LYVE-1, D2-40, Prox-1, and CD31; and no staining of the negative marker CD34. In total, 456 patients were enucleated; 16 of the 46 uveal melanomas with extrascleral extension were contained in stored paraffin tissue. Two samples of the 16 uveal melanomas showed focal positive intraocular vascular staining for LYVE-1 and co-expression of CD31 and CD34. Due to the lack of Prox-1 and D2-40, and positive expression of CD34, these cannot be classified as lymphatic vessels. In one case recruitment of an extraocular, intratumoral lymphatic vascular structure was observed in the periphery of the subconjunctival extrascleral extension. Intraocular lymphatic vessels are absent in uveal melanomas with extrascleral extension; however, we provide proof for recruitment of intratumoral lymphatics by uveal melanomas with extraocular extension from subconjunctival lymphatics that may explain the rare cases of regional lymphatic spread. A panel of antibodies is necessary to detect lymphatic vessels with high specificity.
Quantifying Tubulin Concentration and Microtubule Number Throughout the Fission Yeast Cell Cycle

The fission yeast Schizosaccharomyces pombe serves as a good genetic model organism for the molecular dissection of the microtubule (MT) cytoskeleton. However, analysis of the number and distribution of individual MTs throughout the cell cycle, particularly during mitosis, in living cells is still lacking, making quantitative modelling imprecise. We use quantitative fluorescent imaging and analysis to measure the changes in tubulin concentration and MT number and distribution throughout the cell cycle at a single MT resolution in living cells. In the wild-type cell, both mother and daughter spindle pole body (SPB) nucleate a maximum of 23 ± 6 MTs at the onset of mitosis, which decreases to a minimum of 4 ± 1 MTs at spindle break down. Interphase MT bundles, astral MT bundles, and the post anaphase array (PAA) microtubules are composed primarily of 1 ± 1 individual MT along their lengths. We measure the cellular concentration of αβ-tubulin subunits to be ~5 µM throughout the cell cycle, of which one-third is in polymer form during interphase and one-quarter is in polymer form during mitosis. This analysis provides a definitive characterization of αβ-tubulin concentration and MT number and distribution in fission yeast and establishes a foundation for future quantitative comparison of mutants defective in MTs.
Antithrombotic Therapy for Stroke Prevention.

Recently published 5-year outcomes of 3847 patients with transient ischemic attack (TIA) and minor ischemic stroke managed by stroke experts are sobering.1 The rate of stroke and other cardiovascular events was high in the first year (6.4%), and equally high (6.4%) in the second through fifth years. These findings reiterate that TIA and ischemic stroke patients have pathologies, such as atherosclerosis, that behave prognostically like volcanoes; episodes of acute instability punctuate indolent, if not malignant, progression. The eventful prognosis, despite best therapy, questions the validity of the term “stable” vascular disease and reinforces the need for vigilant long-term evidence-based clinical management complemented by research into new strategies of stroke prevention. Several recent studies inform antithrombotic therapy for stroke prevention.2–5 First, the benefits of aspirin immediately after TIA and ischemic stroke appear greater, but shorter-lived, than recognized previously; aspirin reduces the rate and severity of early recurrent stroke over the first 6 to 12 weeks by more than half, but its effectiveness attenuates with longer-term use.2 Second, the benefits of adding clopidogrel to aspirin, initially reported in a Chinese population, have now been validated externally in a large international population of 4881 patients with acute, noncardioembolic TIA and mild ischemic stroke.3 Third, triple antiplatelet therapy with aspirin, clopidogrel, and dipyridamole is not more effective than clopidogrel alone or combined aspirin and dipyridamole in reducing the incidence and severity of early recurrent stroke, and significantly increases the risk of major bleeding. Fourth, for patients with stable atherosclerotic peripheral and coronary artery disease, including a subgroup with previous nonlacunar ischemic stroke, adding low-dose rivaroxaban (2.5 mg twice daily) to low-dose aspirin (100 mg daily) is more effective than aspirin alone in reducing the rate of stroke, but also causes more major bleeding.4 Fifth, for patients with recent embolic stroke of undetermined source (ESUS), rivaroxaban 15 mg daily is not more effective than aspirin in preventing recurrent stroke and is associated with more bleeding.5 These results indicate that patients with acute, noncardioembolic TIA and mild ischemic stroke should be treated immediately, within 12–24 hours, with a loading dose of clopidogrel (300–600 mg) and aspirin (at least 162 mg), followed by maintenance doses of clopidogrel (75 mg per day) and aspirin (50–325 mg per day) for about 21 days. Thereafter, clopidogrel or aspirin monotherapy or the combination of aspirin plus extended-release dipyridamole is recommended for these patients, and now for patients with ESUS also (Table). 5 However, the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) results in patients with predominantly coronary and peripheral artery atherosclerosis raise the exciting possibility that long-term dual pathway inhibition by low-dose anticoagulation (eg, rivar© 2019 American Heart Association, Inc. PERSPECTIVE
Oral immunization of mice with a probiotic Lactobacillus casei constitutively expressing the α-toxoid induces protective immunity against Clostridium perfringens α-toxin

ABSTRACT Clostridium perfringens α-toxin is one of the major virulence factors during C. perfringens infection, causing hemolysis of erythrocytes in various species. Here, genetically engineered Lactobacillus casei (pPG-α/L. casei 393) constitutively expressing the toxoid of C. perfringens α-toxin was generated and its immunogenicity in mice for induction of protective immunity against the α-toxin was evaluated via oral immunization. The α-toxoid was constitutively expressed by pPG-α/L. casei 393 without a specific inducer, as confirmed by western blotting, laser confocal microscopy, and flow cytometry. In an experiment on BALB/c mice to evaluate the oral immunogenicity of pPG-α/L. casei 393, significant levels of a specific secretory IgA (sIgA) antibody in the intestinal mucus and feces and an IgG antibody in the serum of the probiotic vaccine group were detected after booster immunization (p < 0.05) as compared with the pPG/L. casei 393 and PBS control groups. These antibodies effectively neutralized C. perfringens natural α-toxin. Moreover, significantly higher levels of cytokines IL-2, IL-4, IL-10, IL-12, IL-17, and interferon (IFN) γ in the serum and increased proliferation of spleen lymphocytes obtained from mice orally immunized with pPG-α/L. casei 393 were detected. With a commercial C. perfringens type A inactivated vaccine as a control, immune protection provided by the probiotic vaccine against C. perfringens α-toxin was evaluated, and 90% and 80% protection rates were observed, respectively. Therefore, strain pPG-α/L. casei 393 effectively elicited mucosal, humoral, and cellular immunity, suggesting that pPG-α/L. casei 393 is a promising candidate for development of a vaccine against C. perfringens α-toxin.
A prospective study evaluating the impact of implementing the ERAS protocol on patients undergoing surgery for advanced ovarian cancer

Objective Information on the benefits of enhanced recovery after surgery (ERAS) when applied to advanced ovarian cancer() is minimal. The study objectives were to prospectively evaluate whether the implementation of ERAS in AOC patients improves post-operative recovery, and reduces the length of hospital stay (LOHS), without increasing the readmission rate or surgery-related complications; and to investigate ERAS protocol compliance. Methods This was a prospective interventional study carried out at a single university teaching hospital. Patients undergoing laparotomy for advanced ovarian cancer (stages IIb–IV) from March 2017 to February 2018 were managed using an ERAS protocol. The conventional management (CM) period extended from January 2016 to December 2016. The primary outcome was reduction in LOHS. Secondary outcomes were ERAS protocol compliance, incidence of post-operative complications, and readmission rate. Results The CM and ERAS groups each comprised 45 patients. Both the groups were comparable in terms of clinicopathological and operative characteristic. Median LOHS of the full cohort, primary debulking cohort, interval debulking cohort, staging surgery cohort (all 6 vs 4 days; p<0.001), and complex cytoreductive surgery cohort (5 vs 4 days; p=0.019) were significantly reduced in the ERAS group. The overall compliance for the ERAS protocol was 90.6%. Occurrence of moderate or severe (17.8% vs 0%; p=0.003) and ≥grade 2 extended Clavein-Dindo complications (22.2% vs 0%; p=0.001); and hospital stay due to occurrence of complications (31.1% vs 2.2%; p<0.001) were also significantly reduced in the ERAS group. There was no difference in the 30-day readmission rates. Conclusion The results from our investigation suggest that the ERAS program can be successfully implemented in advanced ovarian cancer patients even in low-resource settings provided the program is modified to meet local needs so as not to increase healthcare costs.
The Effect of Pollen Limitation on the Evolution of Mating System and Seed Size in Hermaphroditic Plants

Pollen limitation, when inadequate pollen receipt results in a plant setting fewer seeds and fruits, can reduce plant reproductive success and promote the evolution of self-fertilization as a mechanism of reproductive assurance. However, the effect of pollen limitation on the joint evolution of mating system and seed size is not known. Using an evolutionarily stable strategy resource allocation model, we show that where moderate pollen limitation and strong inbreeding depression select for complete outcrossing, pollen limitation should also increase the optimal seed size. In contrast, pollen limitation should not affect the optimal seed size under complete selfing, in which case ovule fertilization is certain. Under intermediate conditions, a mixed mating system evolves if the probability of ovule fertilization declines as more ovules are produced, so that a selfed seed with inbreeding depression provides equal marginal fitness returns to a larger outcrossed seed that may result from pollen limitation. Under mixed mating, outcrossed seeds should be larger than selfed seeds, and pollen limitation should not affect the optimal size of either outcrossed or selfed seeds. Our results identify a novel pathway through which pollen limitation selects for mixed mating and provide an adaptive explanation as to why selfed seeds are often smaller than outcrossed seeds.
The Virioneuston: A Review on Viral–Bacterial Associations at Air–Water Interfaces

Vast biofilm-like habitats at air–water interfaces of marine and freshwater ecosystems harbor surface-dwelling microorganisms, which are commonly referred to as neuston. Viruses in the microlayer, i.e., the virioneuston, remain the most enigmatic biological entities in boundary surface layers due to their potential ecological impact on the microbial loop and major air–water exchange processes. To provide a broad picture of the viral–bacterial dynamics in surface microlayers, this review compiles insights on the challenges that viruses likely encounter at air–water interfaces. By considering viral abundance and morphology in surface microlayers, as well as dispersal and infection mechanisms as inferred from the relevant literature, this work highlights why studying the virioneuston in addition to the bacterioneuston is a worthwhile task. In this regard, major knowledge gaps and possible future research directions are discussed.
Self-Emulsifying Oral Lipid Drug Delivery Systems: Advances and Challenges

The attempts to oral delivery of lipids can be challenging. Self-emulsifying drug delivery system (SEDDS) plays a vital role to tackle this problem. SEDDS is composed of an oil phase, surfactants, co-surfactants, emulsifying agents, and co-solvents. SEDDS can be categorized into self-nano-emulsifying agents (SNEDDS) and self-micro-emulsifying agents (SMEDDS). The characterization of SEDDS includes size, zeta potential analysis, and surface morphology via electron microscopy and phase separation methods. SEDDS can be well characterized through different techniques for size and morphology. Supersaturation is the phenomenon applied in case of SEDDS, in which polymers and copolymers are used for SEDDS preparation. A supersaturated SEDDS formulation kinetically and thermodynamically inhibits the precipitation of drug molecules by retarding nucleation and crystal growth in the aqueous medium. Self-emulsification approach has been successful in the delivery of anti-cancer agents, anti-viral drugs, anti-bacterial, immunosuppressant, and natural products such as antioxidants as well as alkaloids. At present, more than four SEDDS drug products are available in the market. SEDDS have tremendous capabilities which are yet to be explored which would be beneficial in oral lipid delivery.
First Report of Pseudomonas syringae pv. tomato Race 1 on Tomato in California.

Symptoms of bacterial speck have occurred sporadically in California since 1993 on tomato (Lycopersicon esculentum) cultivars that possess the PTO gene for resistance to Pseudomonas syringae pv. tomato race 0. In 1998, the disease was found on numerous cultivars resistant to race 0 in fields throughout the Sacramento Valley. In several fields, it caused severe defoliation of tomato seedlings. Symptoms included dark brown to black leaf and stem lesions surrounded by yellow halos. Seven isolates were identified as P. syringae pv. tomato based on analysis of whole cell fatty acids (MIDI, Newark, DE; similarity indices of 0.746 to 0.710), carbon utilization profile (Biolog, Hayward, CA; similarity indices of 0.556 to 0.840), and LOPAT results: levan production (+), oxidase reaction (-), potato soft rot (-), arginine dihydrolase production (-), and tobacco hypersensitivity (+) (2). The isolates were identified as race 1 by inoculating greenhouse-grown tomato plants of cv. Ontario 7710, which possesses the PTO gene, and cv. H1916, which is susceptible to both known races of P. syringae pv. tomato. At least eight plants of each cultivar were inoculated with each isolate. Plants were inoculated by spraying leaves with a bacterial suspension mixed with Carborundum or puncturing leaves with needles dipped in the bacterial suspension (107 cells per ml). Controls were inoculated with water. All plants inoculated with the bacteria developed speck symptoms in 6 days. The bacteria were reisolated from all inoculated plants and confirmed as strains of P. syringae pv. tomato. This is the first documentation of P. syringae pv. tomato race 1 in California. This race was previously reported in Canada in 1986 (1). References: (1) M. B. Lawton and B. H. MacNeill. Can. J. Plant Pathol. 8:85, 1986. (2) R. A. Lelliott et al. J. Appl. Bacteriol. 29:470, 1966.
Preclinical Models of Alzheimer's Disease: Relevance and Translational Validity

The only drugs currently approved for the treatment of Alzheimer's Disease (AD) are four acetylcholinesterase inhibitors and the NMDA antagonist memantine. Apart from these drugs, which have minimal to no clinical benefit, the 40‐year search for effective therapeutics to treat AD has resulted in a clinical failure rate of 100% not only for compounds that prevent brain amyloid deposition or remove existing amyloid plaques but also those acting by a variety of other putative disease‐associated mechanisms. This indicates that the preclinical data generated from current AD targets to support the selection, optimization, and translation of new chemical entities (NCEs) and biologics to clinical trials is seriously compromised. While many of these failures reflect flawed hypotheses or a lack of adequate characterization of the preclinical pharmacodynamic and pharmacokinetic (PD/PK) properties of lead NCEs—including their bioavailability and toxicity—the conceptualization, validation, and interrogation of the current animal models of AD represent key limitations. The overwhelming majority of these AD models are transgenic, based on aspects of the amyloid hypothesis and the genetics of the familial form of the disease. As a result, these generally lack construct and predictive validity for the sporadic form of the human disease. The 170 or so transgenic models, perhaps the largest number ever focused on a single disease, use rodents, mainly mice, and in addition to amyloid also address aspects of tau causality with more complex multigene models including other presumed causative factors together with amyloid. This overview discusses the current animal models of AD in the context of both the controversies surrounding the causative role of amyloid in the disease and the need to develop validated models of cognitive function/dysfunction that more appropriately reflect the phenotype(s) of human aged‐related dementias. © 2019 by John Wiley & Sons, Inc.