cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 2715: Hepatotoxicity and oxidative stress biomarker study of peg-coated and non-coated gold nanoparticles in Sprague-Dawley rats

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Nanoparticles (NPs) offer a great possibility for biomedical application, not only to deliver pharmaceutics, but also to be used as novel diagnostic and therapeutic approaches. Currently, there are no data available regarding to what extent the degree of the toxicity and the accumulation of gold nanoparticles (GNPs) are present in in vivo model. The aim of this study was to assess the effects, after oral administration, of poly-ethylene-glycol (PEG) coated and non-coated GNPs on various hepatotoxicity and oxidative stress markers such as alanine (ALT), aspartate aminotransferases and alkaline phosphatase, lipid hydro peroxide (LHP) in the mouse model. Sprague -Dawley rats were exposed to four different concentrations of PEG-coated and non-coated GNPs (12.5, 25, 50 and 100 mg/kg BW) and a control. Samples were collected 24 hours after the last treatment following standard protocols. Exposure to PEG-coated and non-coated GNPs enhanced the activities of serum amino-transferases (ALT/AST), alkaline phosphatases (ALP) and concentration of lipid hydro peroxide compared to control. However, PEG-coated GNPs demonstrated enhanced hepatotoxic effect than non-coated GNPs. The scientific findings reported here suggest that both GNPs have the potential to induce hepatotoxicity in Sprague-Dawley rats through activation of the mechanisms of oxidative stress at a higher level of exposure. However, more studies to clarify the role of encapsulation in the in vivo toxicity of GNPs, are required and parallel comparison is preferred. Keywords: gold nanoparticle (GNP), poly-ethylene-glycol, lipid hydroperoxide, serum aminotransferases, alkaline phosphatases, Sprague-Dawley rats, hepatotoxicity. Citation Format: Anita K. Patlolla, Myeisha Fountain, Paul Tchounwou. Hepatotoxicity and oxidative stress biomarker study of peg-coated and non-coated gold nanoparticles in Sprague-Dawley rats. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2715. doi:10.1158/1538-7445.AM2015-2715
Assessment of effects of atomoxetine in adult patients with ADHD: consistency among three geographic regions in a response maintenance study

A previous study (Upadhyaya et al. in Eur J Psychiatry 2013b; 27:185–205) reported that adults with attention-deficit/hyperactivity disorder (ADHD) demonstrated maintenance of response for up to 25 weeks after initially responding to atomoxetine treatment. In the present report, the consistency of treatment effect across three geographic regions (Europe, United States/Canada [US/Can], and Latin America [Latin Am]) was explored. Data were analyzed from a phase 3, multicenter, randomized, double-blind, maintenance-of-response (randomized withdrawal) trial of atomoxetine versus placebo in adults with ADHD. Patients were randomized to atomoxetine (N = 266) or placebo (N = 258) for 25 weeks. Consistency assessments included the interaction test, pairwise t tests, noninferiority, and the criteria from Basic Principles on Global Clinical Trials (Ministry of Health, Labour and Welfare of Japan 2007). Atomoxetine-treated patients maintained the improved ADHD symptoms relative to placebo-treated patients on the Conners’ Adult ADHD Rating Scale Investigator-Rated: Screening Version 18-Item (CAARS-Inv:SV) total score in all three regions (atomoxetine–placebo mean difference = −4.55, −3.18, and −0.07 for Europe, US/Can, and Latin Am, respectively). For the Latin Am region, the mean change in total score (0.41) was notably smaller for the placebo group than for Europe (5.87) and US/Can (4.39). Similar results were observed for the CAARS-Inv:SV hyperactivity/impulsivity and inattention subscale scores. Overall, patients maintained the response with atomoxetine treatment compared to placebo; however, the magnitude of treatment effect differed among the regions studied, being numerically higher in the EU and US/Can than Latin Am. Trial registration http://www.clinicaltrials.gov/(NCT00700427 ).
Anti-adipogenic Effects and Mechanisms of Ginsenoside Rg3 in Pre-adipocytes and Obese Mice

Red or black ginseng has been reported more powerful than white/fresh ginseng in dealing with various diseases/conditions including obesity. The major reason is that heating/steaming, the process of making red or black ginseng, produces large amount of bioactive compounds including ginsenoside Rg3 (Rg3), which are trace in fresh or white ginseng. In the present study, Rg3 was applied both in pre-adipocytes and obese mice to investigate the anti-adipogenic effects and relevant mechanisms. Our results show that Rg3 dose-dependently inhibited cell differentiation both in 3T3-L1 cells (30, 50 and 100 μM) and human primary pre-adipocytes (HPAs) (10, 20 and 30 μM). This inhibitory effect is accompanied by the attenuation of the expressions of adipogenic markers including peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein alpha (C/EBP-α), fatty acid synthase (FAS), fatty acid binding protein 4 (FABP4) and perilipin. Although dietary intake of Rg3 (0.1mg Rg3/kg diet, 8 weeks) did not significantly affect body weight gain, fat pads and food intake as well as of PPAR-γ expression in fat tissues, we found that hepatic PPAR-γ and C/EBP-α protein expressions and hepatic glutathione reductase and glutathione S-transferase, two major antioxidants molecules were significantly reduced by Rg3. These results suggest that ginsenoside Rg3 may be a potential agent in reducing/preventing obesity.
Influence of Patient-Level Factors on Mode of Delivery among Operative Vaginal Delivery Candidates in Modern Practice.

Objective We aimed to evaluate which patient-level factors influence mode of delivery among candidates for operative vaginal delivery. Study Design Cross-sectional study of candidates for operative vaginal delivery from 18 hospitals over 8 years. Probabilities of mode of delivery were estimated using hierarchical logistic modeling adjusting for clustering within physician and hospital. Results Total 3,771 (64%) women delivered with forceps, 1,474 (25%) vacuums, and 665 (11%) cesareans. Odds of forceps versus vacuum were higher with induction (OR = 2.16, 95% CI: 1.76–2.65), nulliparity (OR = 2.06, 95% CI: 1.59–2.66), epidural (OR = 2.05, 95% CI: 1.19–3.56), maternal indication (OR = 1.53, 95% CI 1.16–2.02), older maternal age (OR 1.18, 95% CI 1.06–1.31 per 5 years), and longer second stage (OR = 1.10, 95% CI: 1.01–1.20 per hour). Odds of cesarean versus operative vaginal delivery were higher with maternal indication (OR = 9.0, 95% CI: 7.23–11.20), a perinatologist (OR = 2.51, 95% CI: 1.09–5.78), longer second stage (OR = 1.79, 95% CI: 1.65–1.93 per hour), older gestational age (OR = 1.10, 95% CI: 1.01–1.20 per week), and longer labor (OR = 1.02, 95% CI: 1.01–1.04 per hour). Conclusion Patient-level factors influence the decision to proceed with an operative vaginal delivery and the choice of instrument, thereby emphasizing the importance of maintaining availability of both forceps and vacuums.
Ethics, Refugees, and the President's Executive Order.

There are different political philosophies about the responsibilities of states regarding whether to accept refugees. While there is a political philosophy that might be called Nationalist in persp...
Old habits die hard: retrospective analysis of outcomes with use of corticosteroids and antibiotics before embryo transfer.

Objective To evaluate clinical pregnancy rates in embryo transfer (ET) cycles with and without peri-implantation corticosteroid and oral antibiotic administration. Design Retrospective cohort study. Setting University-affiliated in vitro fertilization (IVF) clinic. Patient(s) Eight hundred and seventy-six ETs with or without the routine use of methylprednisolone and doxycycline. Intervention(s) Embryo transfer procedures. Main Outcome Measure(s) Clinical pregnancy rates (CPR). Result(s) The CPR with the routine use of methylprednisolone and doxycycline was 56.1% compared with 61.5% after discontinuation of these medications. Ongoing pregnancy rates were 49.5% with medications versus 53.2% without medications. Of the cleavage-stage embryos, 79% underwent assisted hatching; among these, the CPR was 28.7% when treated with corticosteroids and antibiotics compared with 47.4% without medications. Conclusion(s) No statistically significant difference in overall IVF outcomes was noted after the discontinuation of routine peri-implantation corticosteroids and antibiotics. The use of these medications varies across the country and may be a result of habit rather than evidence-based medicine.
Quasar microlensing models with constraints on the Quasar light curves

Quasar microlensing analyses implicitly generate a model of the variability of the source quasar. The implied source variability may be unrealistic yet its likelihood is generally not evaluated. We used the damped random walk (DRW) model for quasar variability to evaluate the likelihood of the source variability and applied the revised algorithm to a microlensing analysis of the lensed quasar RX J1131-1231. We compared the estimates of the source quasar disk and average lens galaxy stellar mass with and without applying the DRW likelihoods for the source variability model and found no significant effect on the estimated physical parameters. The most likely explanation is that unreliastic source light curve models are generally associated with poor microlensing fits that already make a negligible contribution to the probability distributions of the derived parameters.
Potential of a Northern Population of Aedes vexans (Diptera: Culicidae) to Transmit Zika Virus.

Zika virus is an emerging arbovirus of humans in the western hemisphere. With its potential spread into new geographical areas, it is important to define the vector competence of native mosquito species. We tested the vector competency of Aedes vexans (Meigen) from the Lake Agassiz Plain of northwestern Minnesota and northeastern North Dakota. Aedes aegypti (L.) was used as a positive control for comparison. Mosquitoes were fed blood containing Zika virus and 2 wk later were tested for viral infection and dissemination. Aedes vexans (n = 60) were susceptible to midgut infection (28% infection rate) but displayed a fairly restrictive midgut escape barrier (3% dissemination rate). Cofed Ae. aegypti (n = 22) displayed significantly higher rates of midgut infection (61%) and dissemination (22%). To test virus transmission, mosquitoes were inoculated with virus and 16-17 d later, tested for their ability to transmit virus into fluid-filled capillary tubes. Unexpectedly, the transmission rate was significantly higher for Ae. vexans (34%, n = 47) than for Ae. aegypti (5%, n = 22). The overall transmission potential for Ae. vexans to transmit Zika virus was 1%. Because of its wide geographic distribution, often extreme abundance, and aggressive human biting activity, Ae. vexans could serve as a potential vector for Zika virus in northern latitudes where the conventional vectors, Ae. aegypti and Ae. albopictus Skuse, cannot survive. However, Zika virus is a primate virus and humans are the only amplifying host species in northern latitudes. To serve as a vector of Zika virus, Ae. vexans must feed repeatedly on humans. Defining the propensity of Ae. vexans to feed repeatedly on humans will be key to understanding its role as a potential vector of Zika virus.
Unraveling the Role of Structural Order in the Transformation of Electrical Conductivity in Ca2FeCoO6−δ, CaSrFeCoO6−δ, and Sr2FeCoO6−δ

The ability to control the electrical conductivity of solid-state oxides using structural parameters has been demonstrated. A correlation has been established between the electrical conductivity and structural order in a series of oxygen-deficient perovskites using X-ray and neutron diffraction, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and electrical conductivity studies at a wide temperature range, 25–800 °C. The crystal structure of CaSrFeCoO6−δ has been determined, and its stark contrast to Ca2FeCoO6−δ and Sr2FeCoO6−δ has been demonstrated. The Fe/Co distribution over tetrahedral and octahedral sites has been determined using neutron diffraction. There is a systematic increase in the structural order in progression from Sr2FeCoO6−δ (δ = 0.5) to CaSrFeCoO6−δ (δ = 0.8) and Ca2FeCoO6−δ (δ = 0.9) . The oxygen contents of these materials were determined using iodometric titration and TGA. At room temperature, there is an inverse correlatio...
Exploiting Charge-Transfer States for Maximizing Intersystem Crossing Yields in Organic Photoredox Catalysts.

A key feature of prominent transition-metal-containing photoredox catalysts (PCs) is high quantum yield access to long-lived excited states characterized by a change in spin multiplicity. For organic PCs, challenges emerge for promoting excited-state intersystem crossing (ISC), particularly when potent excited-state reductants are desired. Herein, we report a design exploiting orthogonal π-systems and an intermediate-energy charge-transfer excited state to maximize ISC yields (ΦISC) in a highly reducing (E0* = −1.7 V vs SCE), visible-light-absorbing phenoxazine-based PC. Simple substitution of N-phenyl for N-naphthyl is shown to dramatically increase ΦISC from 0.11 to 0.91 without altering catalytically important properties, such as E0*.
Structure of Frequency-Interacting RNA Helicase from Neurospora crassa Reveals High Flexibility in a Domain Critical for Circadian Rhythm and RNA Surveillance

The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH results in an ATP binding site that is undisturbed by crystal contacts and adopts a conformation consistent with nucleotide binding and hydrolysis. Strikingly, this new FRH structure adopts an arch domain conformation that is dramatically altered from previous structures. Comparison of the existing FRH structures reveals conserved hinge points that appear to facilitate arch motion. Regions in the arch have been previously shown to mediate a variety of protein-protein interactions critical for RNA surveillance and circadian clock functions. The conformational changes highlighted in the FRH structures provide a platform for investigating the relationship between arch dynamics and Mtr4/FRH function.
Use of Immunofluorescence Tests for TdT in Human Hematologic Malignancy

Terminal deoxynucleotidyl transferase (TdT) has been established as a valuable clinical tool in the differential diagnosis of acute leukemia. In pediatric disease, TdT is almost uniformly elevated in tumor cells for “T” cell and “Common” acute lymphoblastic leukemia (ALL) and in selected patients with “Pre B” ALL. In adult leukemias TdT is highly elevated in chronic myelogenous leukemia (CML in blast crisis)(30% of cases) and in undifferentiated leukemia (AUL) in acute phase (50% of cases). Patients with acute myeloid leukemia (AML) will occasionally exhibit high levels of TdT activity (10% of cases).1 Detection of TdT in leukemic cells is important clinically because it is indicative of responsiveness of the disease to chemotherapeutic protocols containing vincristine and prednisone.
Causal Inference and the Construction of Predictive Network Models in Biology

With the digital universe now having surpassed the zetabyte threshold, the push is on to expand advanced high-performance computing infrastructures to manage and store this vast digital universe in ways that facilitate mining of the data, and then developing and applying more sophisticated mathematical algorithms to extract knowledge from it. The promise of effectively mining big data is nothing less than achieving a higher level of understanding in nearly every facet of life, from climate change to the complex patterns in financial markets, to the complexity of living systems. The life sciences stand poised to lead in both the generation of big data and the realization of dramatic benefit from it, whether predicting and preventing the next big outbreak or uncovering the best ways to treat, prevent, and cure common human diseases. We can now score variations in DNA across whole genomes; RNA levels and alternative isoforms, metabolite levels, protein levels and protein state information across the transcriptome, metabolome and proteome; methylation status across the methylome; and construct extensive protein–protein and protein–DNA interaction maps, all in a comprehensive fashion and at the scale of populations of individuals. Interactions among these molecular entities define the complex web of biological processes that give rise to all higher-order phenotypes, including disease. The development of analytical approaches that simultaneously integrate different dimensions of data is essential if we are to extract meaning from these large-scale data to elucidate the complexity of living systems. In this chapter I describe a number of analytical approaches aimed at inferring causal relationships among variables in very large-scale datasets by leveraging DNA variation as a systematic perturbation source. The causal inference procedures are also demonstrated to enhance the ability to reconstruct truly predictive, probabilistic causal gene networks that reflect the biological processes underlying complex phenotypes such as disease. By integrating many different dimensions of data simultaneously to construct these networks, I detail examples of how to construct and then apply network models to uncover causal relationships among molecular phenotypes like gene expression and between molecular and high-order traits such as disease.
Consent for Deep Brain Stimulation in Depression: A Perspective From Investigators

Lawrence and colleagues (2019) take a thoughtful approach to an important ethical question and make a meaningful contribution to ongoing studies related to deep brain stimulation (DBS) for treatmen...
The Role of Poly(ADP-Ribose) Polymerase-1 in Cutaneous Wound Healing.

Critical Issue: Chronic nonhealing wounds of the lower extremities resulting in major amputations are a major health problem worldwide. Significance: Diabetes and ischemia are two major etiologies ...
Treatment of Chronobiologic Sleep and Mood Disorders with Light: Theory and Practice

Melatonin is produced by the pineal gland only at night during the dark in both diurnal and nocturnal animals [1,2]. Exposure to light during the night acutely suppresses melatonin production [3,4]. Most animals are exquisitely sensitive to light and will completely suppress their melatonin production when exposed to 10 — 500 lux light.
Nicosulfuron tolerance and population dynamics of woolly cupgrass (Eriochloa villosa)

Woolly cupgrass has a strong tillering ability. In 30 days it produced seven primary tillers, fourteen secondary tillers, and many tertiary tillers when grown in the greenhouse. Tiller bud initiation was much earlier than tiller emergence. Microscopic studies showed that an 11 -day-old woolly cupgrass seedling with the first tiller emerged had aheady initiated nine tiller buds including five primary tiller buds and four secondary tiller buds. Secondary tiller buds were initiated fi-om the primary tiller even before the primary tiller had emerged. Vascular connection between the main stem and the tillers was examined under a light microscope. No evidence was observed suggesting that there was a physical barrier preventing the translocation of herbicides from the main stem. Autoradiographic studies showed that '' C-nicosulfuron was translocated to every tiller bud regardless of herbicide placement on the plant. The mechanism(s) responsible for woolly ciq>grass tiller emergence following nicosulfijron application was not likely due to the herbicide restricting the tiller buds. The strong tillering ability which caused the initiation of numerous tiller buds at the time of nicosulfuron application may contribute to tiller regrowth and new tiller initiation. 17 However, other mechanisms may be important and further research is required. Nomenclature: Nicosulfuron, 2-[[[[(4,6-dimethoxy-2-pyrinudinyl)amino]carbonyl] amino]sulfonyl]-MiV-dimethyl-3-pyridicarboxamide; woolly cupgrass, Eriochloa villosa (Thunb.) Kunth. # ERBVI. Additional index words: Herbicide translocation, paraffin sectioning, tiller initiation, vascular connection, ERBV
An effect of Sm vacancies on the hybridization gap in topological Kondo insulator candidate SmB6

Abstract A necessary element for the predicted topological state in Kondo insulator SmB6 is the hybridization gap which opens in this compound at low temperatures. In this work, we present a comparative study of the in-gap density of states due to Sm vacancies by Raman scattering spectroscopy and heat capacity for samples where the number of Sm vacancies is equal to or below 1%. We demonstrate that hybridization gap is very sensitive to the presence of Sm vacancies. At the amount of vacancies above 1% the gap fills in with impurity states and low temperature heat capacity is enhanced.
Taurine Enhances the Protective Actions of Fish Oil Against D-Galactosamine-Induced Metabolic Changes and Hepatic Lipid Accumulation and Injury in the Rat.

This study has evaluated the effects of a supplementation with taurine (TAU) on the actions of fish oil (FO) against the hypoglycemia, hypoproteinemia, and hepatic accumulation of lipids and liver damage caused by D-galactosamine (GAL) in the rat. To this end, male Sprague-Dawley rats (200–225 g), in groups of 6, were orally treated with physiological saline (2.5 mL, control group), FO (60 mg/kg), TAU (2.4 mmol/kg) or FO-TAU for three consecutive days and before a single oral dose of GAL (400 mg/kg) given on day 3. In parallel, rats receiving only GAL on day 3 or N-acetylcysteine (NAC, 2.4 mmol/kg) for 3 days before GAL served as controls. On day 4 blood samples were collected by cardiac puncture and used to either measure glucose (GLC) or to obtain plasma fractions. Immediately thereafter, the livers were excised, made into a homogenate in phosphate buffered saline pH 7.4, and centrifuged to obtain clear supernatant. Plasma samples were assayed for their total protein (TP), triglycerides (TG), cholesterol (CHOL), phospholipids (PLP), free fatty acids (FFA) and total bilirubin (TB) and direct bilirubin (DB) contents, and for the activities of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP). The liver homogenates were used to measure TG, CHOL, PLP and total lipids (TL) contents. Without exceptions, GAL was found to markedly affect (p < 0.001) all of the experimental parameters examined, with increases occurring in all instances except for the values of the plasma GLC, TP and PLP which were decreased. A pretreatment with either FO or TAU led to significant attenuation of the effects of GAL and which, in most cases, were of similar magnitude. On the other hand, a combined pretreatment with FO plus TAU usually resulted in a greater protection than with either agent alone (p ≤ 0.05). NAC, serving as a reference treatment, was, in most instances, equipotent with FO alone and. in addition, was the only agent that significantly attenuated the increases in both liver weight and liver weight to body weight ratio caused by GAL.
Three-Phase Circuits

The sinusoidal waveform, at a given frequency, is characterized by its amplitude and phase. In a single-phase source we studied so far, it is assumed that a sinusoidal wave is the input. However, keeping the amplitude the same, a source with three sinusoidal waveforms differing in equal amount of phase turns out to be better for electric-power generation, transmission and distribution systems, and in various other practical applications. The resulting circuits exhibit symmetry both with respect to geometrical structure and element values. Circuits with three sources differing in phase by 120∘ and of the same amplitude, called three-phase circuits, are mostly used in electrical power systems.
How Political Contestation Over Judicial Nominations Polarizes Americans’ Attitudes Toward the Supreme Court

Contemporary US Supreme Court nominations are unavoidably and inevitably political. Although observers worry that political contestation over nominations undermines support for qualified nominees and threatens the Court's legitimacy, there is little empirical evidence to support these claims. The authors argue that political contestation over judicial nominations provides cues that shape the public's impressions about nominees and the Court and polarizes public opinion across partisan lines. Data from a conjoint experiment administered in the first days of the Trump presidency support this argument. Political rhetoric attributed to President Trump and Senate Democrats substantially polarized partisans’ views of nominees and evaluations of the Court's legitimacy, with Republicans (Democrats) expressing significantly more (less) favorable attitudes. Additional analyses suggest that contestation generates divergent partisan responses by affecting views about the nominee's impartiality. These findings challenge existing perspectives that depict attitudes toward the judiciary as resistant to partisan considerations and have important implications for the Court's legitimacy in a polarized era.
Altered Resting-State Functional Connectivity in Adolescents is Associated with PTSD Symptoms and Trauma Exposure

Abstract Alterations in resting-state functional connectivity (rsFC) have been demonstrated in Posttraumatic Stress Disorder (PTSD). However, such reports have primarily focused on adult participants, whereas findings in adolescents with PTSD are mixed and not entirely consistent with the adult literature. Here, we examined rsFC in a non-treatment seeking adolescent sample with posttraumatic stress symptoms (PTSS; n = 59) relative to asymptomatic controls (n = 226). We also examined differences between trauma-exposed and non-exposed control subgroups (TEC n = 73 and Non-TEC n = 153) to examine alterations associated with more general trauma exposure. Finally, we compared the PTSS and TEC groups, to confirm that the reported alterations in PTSS were not driven by trauma exposure. Using a seed-based approach, we examined connectivity of default-mode (DMN) and salience (SN) networks, where alterations have been previously reported. Results suggest that PTSS are associated with less within-DMN connectivity and greater SN-DMN connectivity, as well as altered connectivity with attention regions. Trauma exposure is associated with greater within-SN connectivity. Additionally, we report findings from exploratory connectome-based analysis, which demonstrate a number of topological alterations within DMN in the PTSS group. Overall, our findings replicate prior reports of altered rsFC in PTSD and extend them to non-treatment seeking, trauma-exposed adolescents, who did or did not report PTSS. They specifically highlight SN-DMN desegregation, lower within-DMN and greater within-SN connectivity, as well as altered connectivity with attention regions, in trauma-exposed adolescents. Future research is required to confirm that adolescents with diagnosed PTSD have similar/exacerbated connectivity patterns.
Biochemistry and Molecular Biology of Fungal Sterols

Sterols are produced via the ubiquitous isoprenoid pathway which also gives rise to an array of products such as the dolichols and ubiquinone, or components of important molecules such as isopentenyl adenine, heme A, and farnesylated proteins (Ras). Although there are major groups of organisms that cannot produce sterols including insects, parasitic nematodes, and pythiaceous fungi, sterols are widely distributed in nature, where they are required for the growth and/or reproduction of essentially all eukaryotic organisms. With few exceptions, prokaryotes cannot synthesize sterols and, except for some mycoplasmas, they are not required for growth or reproduction. Specific sterols tend to be produced as end products and accumulate in the major groups of organisms, e.g., cholesterol in mammals, and sitosterol in many plants along with cholesterol, stigmasterol, and campesterol. Families of algae tend to accumulate specific sterols such as cholesterol in the red algae (Rhodophyceae) and fucosterol in the brown algae (Phaeophyceae), and others have several predominant sterols which may include 24-methyl and 24-ethylcholesterol and cholesterol (Patterson 1991).
Making smart drugs smarter: The importance of linker chemistry in targeted drug delivery

Smart drugs, such as antibody-drug conjugates, for targeted therapy rely on the ability to deliver a warhead to the desired location and to achieve activation at the same site. Thus, designing a smart drug often requires proper linker chemistry for tethering the warhead with a vehicle in such a way that either allows the active drug to retain its potency while being tethered or ensures release and thus activation at the desired location. Recent years have seen much progress in the design of new linker activation strategies. Herein, we review the recent development of chemical strategies used to link the warhead with a delivery vehicle for preferential cleavage at the desired sites.
Hi-def memories of lo-def scenes.

The study of visual memory is typically concerned with an image’s content: How well, and with what precision, we can recall which objects, people, or features we have seen in the past. But images also vary in their quality: The same object or scene may appear in an image that is sharp and highly resolved, or it may appear in an image that is blurry and faded. How do we remember those properties? Here six experiments demonstrate a new phenomenon of “vividness extension”: a tendency to (mis)remember images as though they are “enhanced” versions of themselves — that is, sharper and higher quality than they actually appeared at the time of encoding. Subjects briefly saw images of scenes that varied in how blurry they were, and then adjusted a new image to be as blurry as the original. Unlike an old photograph that fades and blurs, subjects misremembered scenes as more vivid (i.e., less blurry) than those scenes had actually appeared moments earlier. Follow-up experiments extended this phenomenon to saturation and pixelation – with subjects recalling scenes as more colorful and resolved – and ruled out various forms of response bias. We suggest that memory misrepresents the quality of what we have seen, such that the world is remembered as more vivid than it is.
Phosphorylation of BIK1 is critical for interaction with downstream signaling components.

Botrytis-induced Kinase 1 (BIK1) is a receptor-like cytoplasmic kinase (RLCK) involved in the defense, growth, and development of higher plants. It interacts with various receptor-like kinases (RLKs) such as Brassinosteroid Insensitive 1 (BRI1), Flagellin Sensitive 2 (FLS2), and Perception of the Arabidopsis Danger Signal Peptide 1 (PEPR1), but little is known about signaling downstream of BIK1. In this study, we aimed to identify Arabidopsis thaliana BIK1 (AtBIK1) and Brassica rapa BIK1 (BrBIK1) interacting proteins, which is downstream signaling components in Arabidopsis. In addition, the effect of BIK1 phosphorylation on their interaction were examined. For yeast two hybrid (Y2H) screening, a B. rapa cDNA activation domain (AD) library and an A. thaliana cDNA library were used. Reverse reaction (LR) recombinations of appropriate open reading frames (AtBIK1, BrBIK1, AtRGP2, AtPATL2, AtPP7) in either pDONR207 or pDONR/zeo were performed with the split-YFP destination vectors pDEST-GWVYNE and pDEST-GWVYCE to generate N- or C-terminal fusions with the N- and C-terminal yellow fluorescent protein (YFP) moieties, respectively. Recombined vectors were transformed into Agrobacterium strain GV3101. The described GST-AtBIK1, Flag-AtBIK1, and Flag-BrBIK1 constructs were used as templates for site-directed mutagenesis with a QuikChange XL Site-Directed Mutagenesis Kit (Stratagene). In results, A. thaliana BIK1 (AtBIK1) displays strong autophosphorylation kinase activity on tyrosine and threonine residues, whereas B. rapa BIK1 (BrBIK1) does not exhibit autophosphorylation kinase activity in vitro. Herein, we demonstrated that four proteins (RGP2, PATL2, PP7, and SULTR4.1) interact with BrBIK1 but not AtBIK1 in a Y2H system. To confirm interactions between BIK1 and protein candidates in Nicotiana benthamiana, BiFC analysis was performed and it was found that only BrBIK1 bound the three proteins tested. Three phosphosites, T90, T362, and T368, based on amino acid sequence alignment between AtBIK1 and BrBIK1, and performed site-directed mutagenesis (SDM) on AtBIK1 and BrBIK. S90T, P362T, and A369T mutations in BrBIK1 restored autophosphorylation kinase activity on threonine residues comparable to AtBIK1. However, T90A, T362P, and T368A mutations in AtBIK1 did not alter autophosphorylation kinase activity on threonine residues compared with wild-type AtBIK1. BiFC results showed that BIK1 mutations restored kinase activity led to the loss of the binding activity to RGP2, PATL2, or PP7 proteins. Phospho-BIK1 might be involved in plant innate immunity, while non-phospho BIK1 may regulate plant growth and development through interactions with RGP2, PATL2, and PP7.
Abstract P170: The Association of Serum Potassium with Mortality in Older Community-Dwelling Individuals: The Cardiovascular Health Study (CHS)

Background: High serum potassium (K) is associated with death in chronic kidney disease (CKD) patients, and in acute illness. Associations in other settings are uncertain. We determined associations between K concentrations and total mortality, coronary heart disease (CHD) death, and sudden cardiac death (SCD) in an older, community-dwelling population. Methods: Among 5137 CHS participants aged ≥ 65 years at baseline, we evaluated associations between serum K categories [< 4.0, 4.0-4.5, 4.5-5.0, & ≥ 5.0 mMol/dL] with CHD death, SCD, and all-cause mortality using Cox proportional hazards models. We also evaluated whether associations differed by angiotensin converting enzyme (ACE) inhibitor / angiotensin II receptor blocker (ARB) use, diuretic use, and CKD status [eGFR < 60 vs. higher]. All CHD and SCD events were adjudicated by committee. Results: Mean age was 72 years, 39% were male, and 17% were Black. Individuals in the ≥ 5.0 mMol/dL category were older, more frequently men, diabetic, to have CKD, and to use ACE/ARBs. They were also less likely to use diuretics. Mean follow-up was 14 ± 6 years during which there were 4122 total deaths including 971 CHD deaths. Follow-up for SCD was 12 ± 5 years during which there were 162 SCD events. In models adjusted for demographics, CVD risk factors, eGFR, and use of ACE/ARBs, diuretics and K supplements, those with K ≥ 5.0 mMol/dL had 32% higher risk of all-cause mortality (HR 1.32; 95% CI: 1.07-1.63) than the 4.0-4.5mMol/dL reference category. The association was similar irrespective of diuretic or ACE/ARB use or by CKD status (pinteraction all > 0.18). Those with K < 4.0 mMol/dL had 14% higher risk of all-cause mortality (HR 1.14; 95% CI: 1.05-1.23) than the reference category; and this association was limited to those with K < 4.0 mMol/dL and were not on diuretics and did not have CKD (pinteraction both < 0.02). No association of K < 4.0 mMol/dL with mortality was observed in those on diuretics or with CKD. There was no significant association of either high or low K with either CHD death (HR 1.08; 95% CI: 0.71-1.65; and HR 0.96; 95% CI: 0.81-1.13, respectively) or SCD (HR 1.13; 95% CI: 0.41-3.11; and HR 1.01; 95% CI: 0.68-1.50, respectively) in adjusted models. Conclusions: Higher and lower serum K are independently associated with all-cause mortality but not CHD death or SCD in older community-dwelling individuals. Mechanisms linking high and low K with mortality from diseases other than CHD and SCD require future study.
Physiology and Culture of Pollen

Publisher Summary The most widely used method for the culture of pollen in vitro has been the hanging drop technique. Pollen grains are placed in a drop of liquid or agar medium on a cover glass which is then inverted over the well of a cavity slide, and its edges are sealed with lanolin or mineral oil. This method allows microscopic examination and the cultures are easy to handle and store. Pollen grains can also be cultured on the surface of media spread evenly on microscopic slides; such open-face cultures require storage in humid chambers. Large quantities of pollen can be collected by obtaining mature anthers and allowing these to dehisce in desiccators. Several mechanical devices, using mild air suction, are used for collecting pollen from plants in the field. Appreciable amounts of pollen grains can also be collected with the help of bees. Pollen grains cultured in dense and large populations germinate better and form longer pollen tubes than pollen germinated in small and evenly distributed populations in the same medium. Pollen grains of many species are known to contain relatively large amounts of plant growth substances, particularly auxins and gibberellins. Therefore, the additional amounts of plant growth substances supplied exogenously to pollen fail to produce any marked improvement in pollen germination and pollen tube growth.
Peramivir: an intravenous neuraminidase inhibitor.

Introduction: Peramivir (BCX-1812, RWJ-270201) is a highly selective inhibitor of influenza A and B neuraminidase that has recently been approved in the USA by the FDA to treat acute, uncomplicated influenza in adults.Areas covered: This review examines the discovery and development of peramavir as well as its role in the treatment of influenza. Peramivir is currently the only FDA-approved anti-influenza agent that can be given as an intravenous injection, granting it a unique role in therapy with the potential to improve adherence and outcomes in patients who are unable to tolerate oral agents. In vitro, animal, human and safety data are presented as well as information regarding special populations, resistance and drug approval.Expert opinion: Clinical trial data support the use of peramivir to relieve influenza symptoms in acute, uncomplicated influenza, with improvements over placebo similar to those of other approved anti-influenza treatments. The ability to give a one-time injectable dose offers imp...
One-step neural network inversion with PDF learning and emulation

We present two new types of neural networks (both of which can be trained with ordinary error backpropagation) and we present a new algorithm for learning a probability density function (pdf) from example vectors. It is normally difficult to invert a neural network, but for the new bijective neural network, it is efficient to find an input producing any desired output, and such an input is guaranteed to exist and to be unique. Furthermore, it can be used as one component in building a pdf neural network, which is a neural network with a nonnegative output, and for which it is guaranteed that the integral of the output is exactly 1.0 (as in a pdf function). Both of these can be used for supervised learning using standard error backpropagation. Finally, the new pdf learning algorithm is capable of using those networks to learn a pdf given i.i.d. samples drawn from that pdf, and to then generate new vectors from the learned pdf. This, in turn, allows inversion of a function with non-unique inverses, where each inverse is generated with just a single evaluation of the network.
The acquisition of expertise in software engineering education

The authors' goal in this paper is to examine the nature of expertise in software development and then to analyze the components of process education necessary to promote its development. This analysis includes three aspects of expertise: (a) declarative knowledge ("knowledge that"); (b) procedural knowledge ("how to knowledge"); and (c) metacognitive knowledge (self-monitoring, agency, reflection). These "flavors" of knowing play an integral role in software development. Traditional education, with its emphasis on textbooks and lectures as its primary pedagogical tools, can teach declarative knowledge, but that knowledge is not automatically connected with doing. The major impact of process education has been to provide a more effective learning environment that focuses on the development of procedural knowledge. It has become clear that procedural and declarative knowledge alone are not sufficient for the development of expertise. Students need to learn how to reflect on both the problem at hand and on the ways they are solving the problem if they are to become agents for their own improvement. Although process educators are often aware and desirous of facilitating metacognitive knowledge, it is rarely addressed explicitly. In this paper, the authors connect issues of metacognitive knowledge to the evolution of software development skill. Their analysis leads to recommendations for structuring software engineering education activities throughout the students' program of study to maximize the development of all three components of expertise. They include examples from their work on integrating process activities in undergraduate computer science instruction.
Organic and conventional agriculture: Materializing discourse and agro-ecological managerialism

This introduction situates key themesfound in papers given at a recent workshop on thechanging material practices, meanings, and regulationof US organic food production. The context is theemergence of an international bio-politics ofagriculture and food and, more particularly in the US,the contradictions of sustainable agriculturemovements catalyzed by the rapid scaling up of organicagriculture from a niche activity to nascentindustry.
Common Stock Put Options: Gambling Without A Penalty

Companies have recently begun to speculate in their own stock by selling common stock put options. The subsequent exercise of these options often creates a loss of shareholder wealth that is not currently recognized due to antiquated accounting rules. This paper argues that it is clearly time for a change in the accounting treatment of these transactions.
Diagnosing Biliary Malignancy

The most common malignant causes of biliary strictures are pancreatic cancer and cholangiocarcinoma. Differentiating between malignant and benign causes of biliary strictures has remained a clinical challenge. Endoscopic retrograde cholangiopancreatography (ERCP) remains the mainstay and first-line method of tissue diagnosis but has a poor diagnostic yield. This article reviews the causes of biliary strictures, the initial clinical evaluation of biliary obstruction, the diagnostic yield of ERCP-based sampling methods, the role of newer tools in the armamentarium for evaluating strictures, and ways to address the ongoing challenge of stricture evaluation in patients with primary sclerosing cholangitis.
Amplitude of PcP, PcS, ScS, and ScP in deep-focus earthquakes

A systematic study has been made of the ratios of (displacement/period) of PcP, PcS, ScS, and ScP to that of the corresponding incident wave {e.g., (displacement/period)_PcP/(displacement/period)_P}, using intermediate and deep-focus earthquake seismograms. The results indicate that the observed ratios of the horizontal components of the waves that are reflected as P waves (i.e., PcP/P and ScP/S) and that of the vertical component of the waves that are reflected as S waves (i.e., ScS/S and PcS/P) at the mantle-core boundary are considerably larger than the theoretical ones, whereas the observed ratios of the vertical component of the first group and that of the horizontal component of the second group are in fairly good agreement with the theoretical values. Theoretical computations were based on the assumption that in the case of a longitudinal wave the vibration is in the direction of propagation and in the case of a transverse wave the vibration is perpendicular to the direction of propagation. It is further found that the behavior of the direct P and S waves is in accord with the theory, but the vibration of the ground is not in the direction of propagation for PcP and ScP and is not perpendicular to the direction of propagation for PcS and ScS.
Imaging of Rheumatoid Arthritis

Increased awareness of the need for early diagnosis of rheumatoid arthritis and advances in the ability to effectively treat rheumatoid arthritis have made disease remission and maintenance of function a reality for many patients. However, identification of patients who are at risk for erosive disease remains a challenge. As more is learnt about risk factors for disease severity and the role of imaging techniques such as ultrasound and magnetic resonance imaging, the ability to prevent disease progression in the form of joint damage and its attendant deformity and functional limitation will further improve.
GI fellows training time comparison in endoscopic ultrasonography (EUS) alone and EUS with FNA in a teaching hospital

GI fellows training time comparison in endoscopic ultrasonography (EUS) alone and EUS with FNA in a teaching hospital
Management of Plastic Bronchitis With Topical Tissue-type Plasminogen Activator

Plastic bronchitis or cast bronchitis is a rare disease of unclear etiology characterized by formation of airway casts that can lead to life-threatening airway obstruction. There is currently limited data regarding optimal treatment of plastic bronchitis. Several therapies have been suggested, but recurrences are common and mortality remains high. We report the case of a 6-year-old boy with refractory eosinophilic bronchial casts, unresponsive to low-dose systemic corticosteroids, inhaled corticosteroids, azithromycin, and dornase alfa, who was treated successfully and safely with direct instillation of tissue-type plasminogen activator (tPA) to the obstructing casts during flexible bronchoscopy and inhaled tPA. Our case illustrates that the current therapy for plastic bronchitis remains inadequate. To our knowledge, this case is the first to show that direct instillation of tPA can be used safely for treatment of this disease. The use of tPA via direct administration into the airways during bronchoscopy and via a nebulizer appeared to be a safe and effective therapy for plastic bronchitis and should be considered early in the course of the disease to prevent complications of severe airway obstruction.
Possible heart failure exacerbation associated with pregabalin: case discussion and literature review

Pregabalin is an analog of the neurotransmitter gamma-aminobutyric acid that exhibits analgesic, anticonvulsant, and anxiolytic properties. Owing to its pharmacologic properties, the drug has been used worldwide in the management of diabetic peripheral neuropathy, postherpetic neuralgia, generalized anxiety disorder, and social anxiety disorder. Although central nervous system disturbances account for the majority of pregabalin's side effects, dose-dependent peripheral edema and weight gain have also been reported. Recently, three case reports have been published documenting a possible association between pregabalin administration and chronic heart failure decompensation. We present three additional cases of possible heart failure exacerbation in patients with clinically stable heart failure who received pregabalin for neuropathic pain. Additionally, we review the literature addressing the nature and possible etiology for this adverse effect.