Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia‐reperfusion injury in isolated mouse heart

Cytochrome P450 (CYP) epoxygenases CYP2C8 and CYP2J2 generate epoxyeicosatrienoic acids (EETs) from arachidonic acid. Mice with expression of CYP2J2 in cardiomyocytes (αMHC‐CYP2J2 Tr) or treated with synthetic EETs have increased functional recovery after ischemia/reperfusion (I/R); however, no studies have examined the role of cardiomyocyte‐ vs. endothelial‐derived EETs or compared the effects of different CYP epoxygenase isoforms in the ischemic heart. We generated transgenic mice with increased endothelial EET biosynthesis (Tie2‐CYP2C8 Tr and Tie2‐CYP2J2 Tr) or EET hydrolysis (Tie2‐sEH Tr). Compared to wild‐type (WT), αMHC‐CYP2J2 Tr hearts showed increased recovery of left ventricular developed pressure (LVDP) and decreased infarct size after I/R. In contrast, LVDP recovery and infarct size were unchanged in Tie2‐CYP2J2 Tr and Tie2‐sEH Tr hearts. Surprisingly, compared to WT, Tie2‐CYP2C8 Tr hearts had significantly reduced LVDP recovery (from 21 to 14%) and increased infarct size after I/R (from 51 to 61%). Tie2‐CYP2C8 Tr hearts also exhibited increased reactive oxygen species (ROS) generation, dihydroxyoctadecenoic acid (DiHOME) formation, and coronary resistance after I/R. ROS scavengers and CYP2C8 inhibition reversed the detrimental effects of CYP2C8 expression in Tie2‐CYP2C8 Tr hearts. Treatment of WT hearts with 250 nM 9,10‐DiHOME decreased LVDP recovery compared to vehicle (16 vs. 31%, respectively) and increased coronary resistance after I/R. These data demonstrate that increased ROS generation and enhanced DiHOME synthesis by endothelial CYP2C8 impair functional recovery and mask the beneficial effects of increased EET production following I/R. —Edin, M. L. , Wang, Z. J., Bradbury, J. A. , Graves, J. P., Lih, F. B. , DeGraff, L. M. , Foley, J. F. , Torphy, R. , Ronnekleiv, O. K. , Tomer, K. B. , Lee, C. R. , Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia‐reperfusion injury in isolated mouse heart. FASEB J. 25, 3436–3447 (2011). www.fasebj. org
Treating childhood traumatic grief: a pilot study.

OBJECTIVE To examine the potential efficacy and specific timing of treatment response of individual child and parent trauma-focused cognitive-behavioral therapy for childhood traumatic grief (CTG), a condition in which trauma symptoms impinge on the child's ability to successfully address the normal tasks of grieving. METHOD Twenty-two children and their primary caretakers received a manual-based 16-week treatment with sequential trauma- and grief-focused interventions. RESULTS Children experienced significant improvements in CTG, posttraumatic stress disorder (PTSD), depressive, anxiety, and behavioral problems, with PTSD symptoms improving only during the trauma-focused treatment components and CTG improving during both trauma- and grief-focused components. Participating parents also experienced significant improvement in PTSD and depressive symptoms. CONCLUSIONS The timing of improvements in CTG and PTSD symptoms lends support to providing sequential trauma- and grief-focused interventions and to the concept that CTG is related to but distinct from PTSD. The results also suggest the benefit of individual treatment for CTG and for including parents in the treatment of CTG. Randomized, controlled trials are needed to further test the efficacy of this treatment model.
Failure of high-dose acyclovir to prevent cytomegalovirus disease after autologous marrow transplantation.

In a retrospective study, the strategy of giving high-dose acyclovir (500 mg/m2 every 8 h intravenously) from day 5 before transplantation to day 30 after transplantation was evaluated in 266 cytomegalovirus (CMV)-seropositive autograft recipients. the incidence of CMV pneumonia was compared with that in 85 control patients who did not receive high-dose acyclovir. There was no significant difference in the incidence of CMV pneumonia between groups at day 100 (Kaplan-Meier estimates, 6.3% [acyclovir] vs. 7.7% [controls], P = .63) and day 200 after transplantation (7.6% vs. 13.1%, P = .32). The overall rate of patients who presented with CMV disease without preceding excretion from blood, urine, or throat was 77%. CMV pneumonia was fatal in 9 (56%) of 16 acyclovir recipients compared with 5 (63%) of 8 controls (P = 1.0). Survival after transplantation was not different between groups (P = .68). Thus, high-dose acyclovir does not appear to be effective for prevention of CMV disease after autologous transplantation.
A one-tube method of reverse transcription-PCR to efficiently amplify a 3-kilobase region from the RNA polymerase gene to the poly(A) tail of small round-structured viruses (Norwalk-like viruses)

Amplification of a 3-kb genome region from the RNA polymerase gene to the 3' poly(A) tail of small round-structured virus (SRSV) by reverse transcription-PCR (RT-PCR) has been difficult to achieve because of a stable secondary structure in a region between the RNA polymerase gene and the 5' end of the second open reading frame. We have developed a one-tube RT-PCR method to efficiently amplify this region. The method comprises three procedures: purification of poly(A)+ RNA from a starting RNA solution by oligo(dT)30 covalently linked to latex particles, buffer exchange, and continuous RT and PCR in a single tube containing all reaction components. The key elements of this method are (i) first-strand cDNA synthesis with the Superscript II version of RNase H- Moloney murine leukemia virus reverse transcriptase at 50 degrees C for 10 min by using the RNA-oligo(dT)30 hybrid on the latex particles as the template and primer, and (ii) PCR by Taq and Pwo DNA polymerases mixed together with a mixture of 12 phased oligo(dT)25 antisense primers. The detection threshold of the one-tube RT-PCR method was as little as 0.2 ng of the crude RNA used as the source of the template. Using this method, we obtained 3-kb products from 24 SRSV strains previously characterized into four genetic groups. These included 5 P1-A, 4 P1-B, 5 P2-A, and 10 P2-B strains. Because SRSVs have not yet been cultivated in vitro, this novel method should facilitate molecular characterization of SRSVs to provide a firm scientific foundation for improvements and refinements of SRSV diagnostics.
Horizontal cells of the turtle retina. II. Analysis of interconnections between photoreceptor cells and horizontal cells by light microscopy

Criteria were established whereby the chief and accessory members of double cones, red‐, green‐, and blue‐sensitive single cones, and rods could be distringuished form one another in 1‐μm sections through the retinas of Pseudemys scripta elegans and Chelydra serpentina. Criteria included the presence or absence of an oil droplet, the size, color, and radial position of the oil droplet, the size and shape of the inner and outer segments, and the shape and orientation of the connection between the perikaryon and synaptic terminal of each receptor cell.
Hepatitis C Virus Infection Promotes Hepatic Gluconeogenesis through an NS5A-Mediated, FoxO1-Dependent Pathway

ABSTRACT Chronic hepatitis C virus (HCV) infection is often associated with type 2 diabetes. However, the precise mechanism underlying this association is still unclear. Here, using Huh-7.5 cells either harboring HCV-1b RNA replicons or infected with HCV-2a, we showed that HCV transcriptionally upregulated the genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), the rate-limiting enzymes for hepatic gluconeogenesis. In this way, HCV enhanced the cellular production of glucose 6-phosphate (G6P) and glucose. PEPCK and G6Pase gene expressions are controlled by the transcription factor forkhead box O1 (FoxO1). We observed that although neither the mRNA levels nor the protein levels of FoxO1 expression were affected by HCV, the level of phosphorylation of FoxO1 at Ser319 was markedly diminished in HCV-infected cells compared to the control cells, resulting in an increased nuclear accumulation of FoxO1, which is essential for sustaining its transcriptional activity. It was unlikely that the decreased level of FoxO1 phosphorylation was mediated through Akt inactivation, as we observed an increased phosphorylation of Akt at Ser473 in HCV-infected cells compared to control cells. By using specific inhibitors of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS), we demonstrated that HCV infection induced JNK activation via increased mitochondrial ROS production, resulting in decreased FoxO1 phosphorylation, FoxO1 nuclear accumulation, and, eventually, increased glucose production. We also found that HCV NS5A mediated increased ROS production and JNK activation, which is directly linked with the FoxO1-dependent increased gluconeogenesis. Taken together, these observations suggest that HCV promotes hepatic gluconeogenesis through an NS5A-mediated, FoxO1-dependent pathway.
Does Public Scientific Research Complement Private Investment in Research and Development in the Pharmaceutical Industry?

This paper analyzes how pharmaceutical research and development (R&D) investment responds to publicly supported biomedical research performed mainly at universities and nonprofit institutions. New microlevel data on investment, by the U.S. National Institutes of Health, allow measures of public basic and clinical research in seven medical classes to be included in a distributed lag model explaining pharmaceutical R&D investment. Using a panel of medical classes observed over 18 years, the analysis found strong evidence that public basic and clinical research are complementary to pharmaceutical R&D investment and thereby stimulate private‐industry investment. However, differences in the relevance and degree of scientific and market uncertainty between basic and clinical research lead to differences in the magnitude and timing of the pharmaceutical investment response.
Phytoplankton of a mountain lake (L’adové pleso, the Tatra Mountains, Slovakia): Seasonal development and first indications of a response to decreased acid deposition

A one-year study of the phytoplankton of remote mountain lake L’adové pleso (2057 m. a.s.l.), situated in the High Tatra Mountains, was carried out in 2000–2001. Seasonal development of the species structure and depth distribution of biomass, as well as chlorophyll-a concentrations, and chemical characteristics of the lake water were examined. The phytoplankton was made up of a low number of nanoplanktonic unicellular species, mainly flagellates from Cryptophyceae and Chrysophyceae. Plagioselmis lacustris, Cryptomonas cf. erosa and Ochromonas spp. were the most important with regards to both abundance and biomass. The phytoplankton showed a marked seasonal development. During most of the ice-covered period, abundances of phytoplankton remained very low. In regard to the vertical distribution, both species composition and total biomass were clearly stratified during most sampling dates. The amount of chlorophyll-a per unit biovolume varied considerably, and significantly higher values were found on sampling dates with complete or partial ice cover. Our data on pH and phytoplankton were compared with a previous study in 1990–1991 in order to evaluate possible changes associated with the decrease of acid deposition. The extent of episodic acidification of the lake water has diminished both in time and space, and lake water pH has slightly increased. We observed a shift in species composition, and an important increase of total phytoplankton abundance. This could be considered as a first sign of biological response to changing chemical conditions.
The lexicon of the Conductor's gaze

This work presents two studies investigating the existence of a lexicon of gaze in conducting, and its possible different mastery in musicians and laypeople. An observational qualitative study singled out 17 items of gaze used by Conductors in music rehearsal and concert, conveying interactional, affective and musical meanings to musicians in the ensemble, and exploiting four semiotic devices: the Conductor may use the same gaze types as laypeople and with the same meaning (generic codified), or with meaning more specific of musical performance (specific codified), and directly or indirectly iconic gaze items. In a subsequent perceptual study, 8 of the gaze items singled out were submitted to 177 between musicians and naïf subjects asking them to interpret their meanings through open and closed questions. Results show that some gaze items, especially those conveying intensity (piano, forte) and other technical indications (high note, attack) are fairly recognized; yet, no significant differences result between expert and naïf subjects. Gaze constitutes a lexicon also in music performance and exploits the same semiotic devices as gaze in everyday life.2
Editorial 2018

Molecular Ecology continues to perform well. It was the second largest evolutionary biology journal (392 articles) in 2016 according to ISI Web of Knowledge, and had the sixth highest citation impact factor (6.1). In terms of overall impact, Molecular Ecology ranks second among ecology or evolution journals according to Google Scholar’s h5-index, which rates journals by cumulative hindex over the past five years. Our push to streamline the review process over the past year has begun to pay off, and the time to decision on original manuscript submissions averaged 30 days in 2017. We continue in our efforts to enhance the experience of our authors. Wiley has introduced a new page design for Molecular Ecology, which has been optimized for the online environment. Our website has been updated and reformatted to increase usability, and our Author Guidelines have been updated in a format intended to be less “text dense” for our authors. In addition, the scope statement for the journal now appears in both English and Chinese, as we strive to be more welcoming to our Chinese authors. In October 2017, we were most pleased to welcome a dedicated Editorial Assistant, David Crespo, to the Molecular Ecology staff. Many of you may have heard from him already as he manages the molecol email box and patrols our Scholar One Manuscript Central site. Thus, we expect that the editorial office will be able to respond more quickly to author questions and concerns in 2018.
The role of constructors in the context of refactoring object-oriented systems

Constructors play an essential role in object-oriented (OO) languages as a means of object creation. Yet, very little empirical evidence exists on constructors, trends in their composition and how they impact comprehension and encapsulation of OO classes. In this paper, we empirically investigate the opportunities, benefits and problems of refactoring class constructors across a sample of classes from five Java systems. The refactoring used, namely, replacing multiple constructors with creation methods, was applied to each of a set of classes containing three or more constructors. Empirical results showed benefits in terms of removed (duplicated) lines of code across the majority of systems. They also showed the potential for improved class comprehension by the creation of non-constructor methods (as a replacement for constructors) and improved encapsulation of class elements through use of a private catch-all constructor. We also provide evidence from five C++ systems which suggests similar trends in constructors to those found for Java. In terms of problems encountered, frequent and inconsistent use of the super construct made refactoring prohibitively difficult in some cases; the existence of Java interfaces also means a lack of scope for constructor refactoring. The results indicate clear and tangible benefits to be gained from investigation and implementation of refactoring techniques in Java, but with caution being exercised in certain cases; refactoring in practice is not as straightforward as the theory suggests.
Studies on Trypanosoma (nannomonas) congolense: III. Antigenic variation in three cyclically transmitted stocks

Summary Cyclical transmission of different variable antigen types of Trypanosoma congolense STIB 228 resulted in the development of metacyclic trypanosome populations which were similar in their variable antigen composition as judged by immunofluorescence and neutralization assays. The variable antigen types present in the ingested bloodstream populations were not found in the metacyclic populations. The bloodstream populations which were obtained from cyclically infected, irradiated (900 rad.) mice contained variable antigen types which were not present in the corresponding metacyclic populations. When derivatives of 2 other stocks of T. congolense, isolated in a different area of Tanzania, underwent cyclical development in the tsetse fly, the metacyclic populations of each stock also had a characteristic variable antigen composition. The metacyclic populations of the 3 stocks were, however, completely dissimilar in variable antigen composition. Simultaneous infection of tsetse flies with a mixture of different stocks resulted in the concurrent production of metacyclic trypanosomes which contained the characteristic variable antigen types of each stock. The effect of cyclical transmission on the process of antigenic variation in T. congolense infections is therefore similar to that in T. brucei infections.
Isolation and Characterization of Two Parasitic Protozoa from a Pacific Harbor Seal (Phoca Vitulina Richardsi) With Meningoencephalomyelitis

Two species of protozoans were isolated from a harbor seal with fatal meninogoencephalitis. Serologic reactivity was detected to both Sarcocystis neurona and Toxoplasma gondii. Parasites associated with brain inflammation and necrosis reacted only with immunohistochemical stains utilizing polyclonal antisera raised against Sarcocystis neurona. However, 2 distinct parasites were observed in cell cultures derived from the seal's brain tissue. These parasites were separated by mouse passage and limiting dilution. Purified zoites from 1 isolate (HS1) reacted strongly with polyclonal antiserum to S. neurona and with the harbor seal's own serum (1:2,560 for each) on indirect immunofluorescent antibody tests (IFAT), but weakly to antisera to T. gondii and Neospora caninum (1:40). Zoites from the second isolate (HS2) reacted positively with T. gondii polyclonal antiserum (1:81,920) and with the harbor seal's own serum (1:640), but weakly to S. neurona and N. caninum antisera (1:80 or less). Amplification and sequence analysis of protozoal DNA encoding portions of the 18s ribosomal RNA (18s rDNA) and the adjacent first internal transcribed spacer (ITS1) were performed for both isolates, and resulting sequences were compared to those from similar protozoans. Based on molecular characterization, parasite morphology, serologic reactivity, histology, and immunohistochemistry, HS1 was indistinguishable from S. neurona, and HS2 was indistinguishable from T. gondii.
Interplay between virus and host cells by

Heidi Berghäll Measles virus infection – Interplay between virus and host cells Department of Virology, University of Turku, Turku, Finland Annales Universitatis Turkuensis Measles, caused by measles virus (MV), is a highly contagious viral disease causing severe respiratory infection and a typical rash. Despite the availability of a protective vaccine, measles is still the leading vaccine-preventable cause of childhood mortality worldwide. The high mortality associated with the disease is mainly due to an increased susceptibility to secondary infections during the period of immunosuppression that continues for several weeks after recovery. The present study was undertaken to elucidate the role of cytoskeletal components in the regulation of MV infection. The most interesting finding was that MV replication was activated in unstimulated peripheral blood mononuclear cells (PBMC) when globular actin was converted into the filamentous form with jasplakinolide. This provides a new aspect in our understanding of MV infection in PBMC. In the second part of the thesis we investigated MV-induced structural changes of cellular nuclear matrix, which is a proteinaceous framework of the nucleus similar to the cytoskeleton in the cytoplasm. We showed that cleavage of nuclear markers was virusspecific and a general caspase inhibitor rescued MV-infected cells from cell death. Furthermore, we studied MV-induced innate immune mechanisms in lung epithelial and endothelial cells. Our results showed that MV infection resulted in activation of the double stranded RNA (dsRNA) binding molecules melanoma differentiation-associated gene 5 (mda-5), retinoic acid inducible gene I (RIG-I), and toll-like receptor 3 (TLR3) gene expression, followed by high expression of antiviral cytokine mRNA.
Sub-Micrometric Liposomes as Drug Delivery Systems in the Treatment and Periodontitis

Periodontitis is a complex disease and bacterial infection is one of the most common factors involved in this disease. Current strategies for the local delivery of antibiotics do not allow a complete clearance of bacteria filling dentinal tubules and this limits their therapeutic efficacy. Therefore, there is a strong need for the development of new delivery strategies aimed at improving the efficacy of antibiotic therapy for periodontitis with special reference to their ability to penetrate into the tubules. The aim of the present study is to develop liposome-based delivery systems of sub-micron dimension, able to diffuse into the dentinal tubules. A further aim of the research is to develop a protocol for enhanced diffusion based on the use of magnetic liposomes and magnetic fields. Liposomes were produced by hydration of a pre-liposomal formulation. The vesicles were stabilised with PEG and their re-sizing was achieved by extrusion. Magnetite nanoparticles were synthesized inside the vesicles, i.e., the chemical reaction involving FeCl2, FeCl3 and NH3 occurred within the core of the newly formed liposomes. Dynamic Light Scattering analysis was performed for size characterization. A mathematical model was implemented to predict the diffusion of the liposomes in dentinal tubules. Ex-vivo validation was performed on extracted human teeth. We produced PEG-ylated liposomes (average size 204.3 nm) and PEG-ylated magnetic liposomes (average size 286 nm) and an iron content of 4. 2μg/ml. Through mathematical modelling, we deduced that sub-micrometer vesicles are able to penetrate into dentinal tubules. This penetration is considerably more effective when the vesicles are magnetized and subjected to an external magnetic field which accelerates their movement within the tubules. The liposome-based delivery systems developed by the present study are able to penetrate deeply into the tubules, sometimes reaching their terminal ends.