Miracle-dz/UniFAR-FTUs huggingface dataset:
Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate

Epidemiological evidence links consumption of lycopene, the red carotenoid of tomato, to reduced prostate cancer risk. We investigated the effect of lycopene in normal prostate tissue to gain insight into the mechanisms, by which lycopene can contribute to primary prostate cancer prevention. We supplemented young rats with 200 ppm lycopene for up to 8 wk, measured the uptake into individual prostate lobes, and analyzed lycopene‐induced gene regulations in dorsal and lateral lobes after 8 wk of supplementation. Lycopene accumulated in all four prostate lobes over time, with all‐trans lycopene being the predominant isoform. The lateral lobe showed a significantly higher total lycopene content than the other prostate lobes. Transcriptomics analysis revealed that lycopene treatment mildly but significantly reduced gene expression of androgen‐metabolizing enzymes and androgen targets. Moreover, local expression of IGF‐I was decreased in the lateral lobe. Lycopene also consistently reduced transcript levels of proinflammatory cytokines, immunoglobulins, and immunoglobulin receptors in the lateral lobe. This indicates that lycopene reduced inflammatory signals in the lateral prostate lobe. In summary, we show for the first time that lycopene reduced local prostatic androgen signaling, IGF‐I expression, and basal inflammatory signals in normal prostate tissue. All of these mechanisms can contribute to the epidemiologically observed prostate cancer risk reduction by lycopene.
Ankle biomechanics during four landing techniques.

PURPOSE An understanding of landing techniques is important for the prevention of injuries in a number of athletic events. There is a risk of injury to the ankle during landings, and the kinematics and forces involved in different landing strategies may be related to the occurrence of trauma. METHODS In the current study, four drop conditions from a 30.48-cm (12-inch) height were tested. The conditions were a) BN: Bent knee (self-selected), Natural (self-selected) plantar flexor contraction; b) SN: Stiff-knee, Natural plantar flexors; c) SP: Stiff-knee, Plantar flexors absorbing the impact; and d) SH: Stiff-knee, absorbing most of the impact in the Heels. Peak vertical forces and accelerations were measured, and Achilles tendon forces and stiffnesses were calculated. RESULTS Peak vertical forces and peak tibial accelerations were highest for the SH condition (2418 N and 20.7 G), whereas peak Achilles tendon force was highest for SP drops. The overall average AT stiffness was 166,345 N x m(-1). CONCLUSIONS The results from the study were used in an extensive cadaver study to investigate ankle injuries. The data from the current study indicate that athletes may not use their full energy absorbing potential in landings during sporting activities.
Uric acid and transforming growth factor in fructose-induced production of reactive oxygen species in skeletal muscle.

The consumption of fructose, a major constituent of the modern diet, has raised increasing concern about the effects of fructose on health. Research suggests that excessive intake of fructose (>50 g/d) causes hyperuricemia, insulin resistance, mitochondrial dysfunction, de novo lipogenesis by the liver, and increased production of reactive oxygen species (ROS) in muscle. In a number of tissues, uric acid has been shown to stimulate the production of ROS via activation of transforming growth factor β1 and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4. The role of uric acid in fructose-induced production of ROS in skeletal muscle, however, has not been investigated. This review examines the evidence for fructose-induced production of ROS in skeletal muscle, highlights proposed mechanisms, and identifies gaps in current knowledge.
The Eurasian Economic Union- approaching the economic integration in the post-Soviet space by EU-emulated elements

Le processus d’integration economique regionale dans l’espace post-sovietique a ete initiepresque dans le meme temps avec la dissolution de l’URSS. Il a commence avec la creation de la Communaute des Etats independants (CEI), suivi par les initiatives regionales menees par les republiques d’Asie centrale et les projets sous-regionaux de la CEI entraines par la Russie. Toutefois, avant la creation de la Communaute economique eurasiatique (CEEA), ces projets d’integration economique ont montre lacunes importantes concernant la conception institutionnelle. La creation de la CEEA indique la nouvelle approche de la Russie sur l’integration economique regionale dans l’espace post-sovietique, qui sera desormais effectuee par un haut degre d’institutionnalisation et de legalisation et par l’emulation du projet europeen dans l’architecture institutionnelle des nouvelles institutions. Par la suite, l’emulation de l’UE s’est manifestee dans la creation de l’Union douaniere eurasiatique (UDA), et notamment dans la creation de l’Union economique eurasiatique (UEEA). Ces organisations etablissent des regimes juridiques institutionnalises avec des effets contraignants, renforces par des mecanismes de reglement des differends, par le transfert des competences et la creation d’une bureaucratie supranationale. D’avantage, l’emulation de l’UE se manifeste plus largement dans la conception institutionnelle de l’UEEA que dans celle de l’UDA, car elle a inspire non seulement l’introduction des restrictions et des regles d’ethique regissant l’activite de la bureaucratie supranationale, mais egalement la creation des politiques «convenus» et «coordonnees», et la future mise en place des marches communs et d’un espace economique commun.
Cell Entry of Hepatitis C Virus Requires a Set of Co-receptors That Include the CD81 Tetraspanin and the SR-B1 Scavenger Receptor*

Several cell surface molecules have been proposed as receptor candidates, mediating cell entry of hepatitis C virus (HCV) on the basis of their physical association with virions or with soluble HCV E2 glycoproteins. However, due to the lack of infectious HCV particles, evidence that these receptor candidates support infection was missing. Using our recently described infectious HCV pseudotype particles (HCVpp) that display functional E1E2 glycoprotein complexes, here we show that HCV is a pH-dependent virus, implying that its receptor component(s) mediate virion internalization by endocytosis. Expression of the CD81 tetraspanin in non-permissive CD81-negative hepato-carcinoma cells was sufficient to restore susceptibility to HCVpp infection, confirming its critical role as a cell attachment factor. As a cell surface molecule likely to mediate endosomal trafficking, we demonstrate that the human scavenger receptor class B type 1 (SR-B1), a high-density lipoprotein-internalization molecule that we previously proposed as a novel HCV receptor candidate due to its affinity with E2 glycoproteins, is required for infection of CD81-expressing hepatic cells. By receptor competition assays, we found that SR-B1 antibodies that blocked binding of soluble E2 could prevent HCVpp infectivity. Furthermore, we establish that the hyper-variable region 1 of the HCV E2 glycoprotein is a critical determinant mediating entry in SR-B1-positive cells. Finally, by correlating expression of HCV receptors and infectivity, we suggest that, besides CD81 and SR-B1, additional hepatocyte-specific co-factor(s) are necessary for HCV entry.
Lectins selectively label cartilage condensations and the otic neuroepithelium within the embryonic chicken head

Cartilage morphogenesis during endochondral ossification follows a progression of conserved developmental events. Cells are specified towards a prechondrogenic fate and subsequently undergo condensation followed by overt differentiation. Currently available molecular markers of prechondrogenic and condensing mesenchyme rely on common regulators of the chondrogenic program that are not specific to the tissue type or location. Therefore tissue‐specific condensations cannot be distinguished based on known molecular markers. Here, using the chick embryo model, we utilized lectin labeling on serial sections, demonstrating that differential labeling by peanut agglutinin (PNA) and Sambucus nigra agglutinin (SNA) successfully separates adjacently located condensations in the proximal second pharyngeal arch. PNA selectively labels chick middle ear columella and basal plate condensation, whereas SNA specifically marks extracolumella and the ventro‐lateral part of the otic capsule. We further extended our study to examine lectin‐binding properties of the different parts of the inner ear epithelium, neural tube and notochord. Our results show that SNA labels the auditory and vestibular hair cells of the inner ear, whereas PNA specifically recognizes the statoacoustic ganglion. PNA is also highly specific for the floor plate of the neural tube. Additionally, wheat germ agglutinin (WGA) labels the basement membrane of the notochord and is a marker of the apical‐basal polarity of the cochlear duct. Overall, this study indicates that selective lectin labeling is a promising approach to differentiate between contiguously located mesenchymal condensations and subregions of epithelia globally during development.
Light-Evoked Excitatory and Inhibitory Synaptic Inputs to ON and OFF α Ganglion Cells in the Mouse Retina

Bipolar cell and amacrine cell synaptic inputs to α ganglion cells (αGCs) in dark-adapted mouse retinas were studied by recording the light-evoked excitatory cation current (ΔIC) and inhibitory chloride current (ΔICl) under voltage-clamp conditions, and the cell morphology was revealed by Lucifer yellow fluorescence with a confocal microscope. Three types of αGCs were identified. (1) ONαGCs exhibits no spike activity in darkness, increased spikes in light, sustained inward ΔIC, sustained outward ΔICl of varying amplitude, and large soma (20–25 μm in diameter) withα-cell-like dendritic field ∼180–350 μm stratifying near 70% of the inner plexiform layer (IPL) depth. (2) Transient OFFαGCs (tOFFαGCs) exhibit no spike activity in darkness, transient increased spikes at light offset, small sustained outward ΔIC in light, a large transient inward ΔIC at light offset, a sustained outward ΔICl, and a morphology similar to the ONαGCs except for that their dendrites stratified near 30% of the IPL depth. (3) Sustained OFFαGCs exhibit maintained spike activity of 5–10 Hz in darkness, sustained decrease of spikes in light, sustained outward ΔIC, sustained outward ΔICl, and a morphology similar to the tOFFαGCs. By comparing the response thresholds and dynamic ranges of αGCs with those of the preganglion cells, our data suggest that the light responses of each type of αGCs are mediated by different sets of bipolar cells and amacrine cells. This detailed physiological analysis complements the existing anatomical results and provides new insights on the functional roles of individual synapses in the inner mammalian retina.
Development of clinical‐quality registries in Australia: the way forward

Australia is developing a national performance framework aimed at measuring health outcomes across the health system. Clinical registries provide a clinically credible means of monitoring health care processes and outcomes, yet only five Australian registries currently have national coverage. At a national level, clinical registry development should be prioritised to target conditions or procedures that are suspected of being associated with large variations in processes or outcomes of care and that impact significantly on health care costs and patient morbidity. Registries should also aim to capture information across care interfaces and to monitor the medium and long‐term safety and effectiveness of specific devices, procedures and drugs.
Immuno-PET of Cancer: A Revival of Antibody Imaging

With the identification of tumorassociated antigens more than 30 y ago and the development of hybridoma technology in 1975, investigators realized that Paul Ehrlich’s vision to effectively target drugs to diseased tissues could be tested. It was shown that monoclonal antibodies could specifically target tumors (1,2), and it was hypothesized that cancer could be treated with naked antibodies by inducing antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, or apoptosis or with antibodies tagged with cytotoxic drugs or radionuclides. Indeed, in the early
The Cellular RNA Export Receptor TAP/NXF1 Is Required for ICP27-Mediated Export of Herpes Simplex Virus 1 RNA, but the TREX Complex Adaptor Protein Aly/REF Appears To Be Dispensable

ABSTRACT Herpes simplex virus 1 (HSV-1) protein ICP27 has been shown to shuttle between the nucleus and cytoplasm and to bind viral RNA during infection. ICP27 was found to interact with the cellular RNA export adaptor protein Aly/REF, which is part of the TREX complex, and to relocalize Aly/REF to viral replication sites. ICP27 is exported to the cytoplasm through the export receptor TAP/NXF1, and ICP27 must be able to interact with TAP/NXF1 for efficient export of HSV-1 early and late transcripts. We examined the dynamics of ICP27 movement and its localization with respect to Aly/REF and TAP/NXF1 in living cells during viral infection. Recombinant viruses with a yellow fluorescent protein (YFP) tag on the N or C terminus of ICP27 were constructed. While the N-terminally tagged ICP27 virus behaved like wild-type HSV-1, the C-terminally tagged virus was defective in viral replication and gene expression, and ICP27 was confined to the nucleus, suggesting that the C-terminal YFP tag interfered with ICP27's C-terminal interactions, including the interaction with TAP/NXF1. To assess the role of Aly/REF and TAP/NXF1 in viral RNA export, these factors were knocked down using small interfering RNA. Knockdown of Aly/REF had little effect on the export of ICP27 or poly(A)+ RNA during infection. In contrast, a decrease in TAP/NXF1 levels severely impaired export of ICP27 and poly(A)+ RNA. We conclude that TAP/NXF1 is essential for ICP27-mediated export of RNA during HSV-1 infection, whereas Aly/REF may be dispensable.
Basal Anthropoids from Egypt and the Antiquity of Africa's Higher Primate Radiation

Early anthropoid evolution in Afro-Arabia is poorly documented, with only a few isolated teeth known from before ∼35 million years ago. Here we describe craniodental remains of the primitive anthropoid Biretia from ∼37-million-year-old rocks in Egypt. Biretia is unique among early anthropoids in exhibiting evidence for nocturnality, but derived dental features shared with younger parapithecids draw this genus, and possibly >45-million-year-old Algeripithecus, into a morphologically and behaviorally diverse parapithecoid clade of great antiquity.
FRI0280 Cd4+cd25highfoxp3+ t regulatory cells as a biomarker of disease activity in systemic lupus erythematosus: a prospective study

Background Low numbers of T regulatory cells (Tregs) in active systemic lupus erythematosus (SLE) are believed to reflect the breakdown of immune tolerance in disease pathogenesis. However, it is not clear if these cells may be utilized as a biomarker in assessing disease activity. Objectives of the present study was the prospective evaluation of Tregs as possible biomarkers in assessing SLE activity. Methods Tregs (phenotype CD4+CD25highFOXP3+) were assessed by flow cytometry in 285 separate blood samples from 100 white Caucasian SLE patients and 20 healthy controls. Patients were divided, according to disease activity (as measured by Systemic Lupus Erythematosus Disease Activity Index, SLEDAI) into groups A (n=39, samples=94, SLEDAI=0), B (n=33, samples=92, SLEDAI=1-5), C (n=10, samples=53, SLEDAI=6-10) and D (n=18, samples=46, SLEDAI>10). Longitudinal measurements were performed in 131 cases (37 relapses, 44 remissions and 50 cases without alteration in disease activity). Statistics were performed by Student’s t-test or one-way ANOVA, post hoc analysis with Bonferroni multiple comparisons test and correlations with Pearson co-efficient; while p<0.05 was considered significant. Results Tregs were found significantly lower in severely active disease (group D), compared to healthy controls, inactive disease, mild and moderate disease activity (0.57±0.16% vs. 1.49±0.19%, 1.19±0.34% and 1.05±0.36%, 0.72±0.21%, p<0.05, respectively). There was a strongly inverse correlation between Tregs and SLEDAI (r=-0.644, p<0.001). Alterations in disease activity were characterized by inverse alterations in Tregs: relapse (from 1.23±0.44% to 0.64±0.19%, p<0.001, mean change 0.59±0.41%), remission (from 0.65±0.27% to 1.17±0.30%, p<0.001, mean change 0.52±0.35%). In cases with unaltered disease activity, Tregs numbers remained stable (from 0.98±0.35% to 1.03±0.34%, p=0.245). Tregs were practically halved during relapse (mean reduction 42.6±22.2%), and doubled during remission (mean increment 113±120.9%). Mean change of Tregs in cases with unaltered activity was significantly lower (7.3±20.6%, p<0.001). A clinically significant change in SLEDAI (sum of cases with relapse and remission, n=81) was followed by a significant (>20%) inverse change in Tregs in 71/81 cases (sensitivity 87.7%). In the 50 cases of unchanged SLEDAI, Tregs were significantly changed (>20%) in 13 cases (specificity 74%). Positive predictive value (PPV) was 84.5% and negative predictive value (NPV) was 78.7%. Conclusions CD4+CD25highFOXP3+ T regulatory cells displayed a strongly inverse correlation to disease activity, while their alterations reflected the changes in SLEDAI with high sensitivity. These cells may be a promising biomarker for the assessment of disease activity in SLE by longitudinal measurements. Disclosure of Interest: None Declared
Diagnostic parameters for monitoring peri-implant conditions.

PURPOSE To review the literature on clinical, radiographic, and biochemical parameters used for monitoring peri-implant conditions. MATERIALS AND METHODS A MEDLINE search was conducted that included articles published in English until the end of August 2003. Results from human and experimental animal studies are presented. RESULTS The parameters that may be used to assess the presence of peri-implant health and the severity of peri-implant disease include plaque assessment, mucosal conditions, peri-implant probing depth, width of the peri-implant keratinized mucosa, periimplant sulcus fluid analysis, suppuration, implant mobility and discomfort, resonance frequency analysis, and radiographic evaluation. DISCUSSION Based on the analysis of the available evidence, it appears reasonable to use a number of clinical and radiographic parameters to discriminate between peri-implant health and disease. CONCLUSIONS Systematic and continuous monitoring of peri-implant tissues during maintenance care is recommended for the early diagnosis of peri-implant disease.
Chronotropic effects of nitric oxide in the denervated human heart

Nitric oxide synthase is expressed in the sino‐atrial node and animal data suggests a direct role for nitric oxide on pacemaker activity. Study of this mechanism in intact humans is complicated by both reflex and direct effects of nitric oxide on cardiac autonomic control. Thus, we have studied the direct effects of nitric oxide on heart rate in human cardiac transplant recipients who possess a denervated donor heart. In nine patients, the chronotropic effects of systemic injection of the nitric oxide synthase inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA) (3 mg kg−1) or increasing bolus doses of the nitric oxide donor, sodium nitroprusside (SNP), were studied. Injection of l‐NMMA increased mean arterial pressure by 17 ± 2 mmHg (mean ±s.e.m.; P < 0.001) and also had a significant negative chronotropic effect, lengthening the R‐R interval by 54 ± 8 ms (P < 0.001). This bradycardia was not reflex in origin since injection of the non‐NO‐dependent vasoconstrictor, phenylephrine (100 μg) achieved a similar rise in mean arterial pressure (18 ± 3 mmHg; P < 0.001) but failed to change R‐R interval duration (ΔR‐R =−3 ± 4 ms). Furthermore, no change in levels of circulating adrenaline was observed with l‐NMMA. Conversely, injection of sodium nitroprusside resulted in a positive chronotropic effect with a dose‐dependent shortening of R‐R interval duration, peak ΔR‐R =−25 ± 8 ms with 130 μg (P < 0.01). These findings indicate that nitric oxide exerts a tonic, direct, positive chronotropic influence on the denervated human heart. This is consistent with the results of animal experiments showing that nitric oxide exerts a facilitatory influence on pacemaking currents in the sino‐atrial node.
Recovery of Midlife Women From Myocardial Infarction

We conducted this qualitative study to elicit the experiences of midlife women who survived myocardial infarctions (MIs) and returned home to recover. We selected a phenomenological research method based on the philosophy of Merleau-Ponty. The researcher interviewed eight women ranging in age from 45 to 65. The interviews were transcribed and analyzed using the approach of Thomas and Pollio. For the women in this study, figural themes of the experience of the MI and recovery must be understood within the existential grounds of the body and others. Themes included the following: (a) interference, (b) freedom/unfreedom, (c) knowing/not knowing, and (d) living in fear. Based on the findings of this study, we suggest that women need to be better educated before leaving the hospital. Returning home post MI was a difficult time, and the women in this study felt a support group for female MI survivors was needed.
Nuclear Accumulation of Cyclin B1 in Mouse Two-Cell Embryos Is Controlled by the Activation of Cdc21

Abstract In the present study, the sequential expression and cellular localization of cyclin B1 was examined in two-cell mouse embryos to elucidate the mechanism of the two-cell block. One-cell embryos derived from in vitro fertilization were cultured with oviductal tissue (nonblocking condition) or without oviductal tissue (blocking condition) to establish the experimental conditions in which the embryos either overcome the two-cell block or do not. The amount of cyclin B1 gradually increased through the second cell cycle (through S to G2 phase). However, the difference was not observed between culture conditions. This showed that even embryos exhibiting the two-cell block normally synthesize cyclin B1 through the cell cycle. Cyclin B1 in embryos cultured under nonblocking condition accumulates in the nucleus during the transition from the G2 to the M phase, whereas that in embryos cultured in blocking condition localizes in the cytoplasm throughout the cell cycle. These data indicate that two-cell embryos cultured in blocking condition are able to normally synthesize cyclin B1 but have defects in nuclear accumulation of the protein. However, when two-cell blocked embryos were treated with okadaic acid, an activator of Cdc2 kinase, part of cyclin B1 in the embryos translocated into the nucleus. Moreover, treatment with butyrolactone I, a specific inhibitor of Cdc2 kinase, inhibits nuclear translocation of cyclin B1 in those embryos. These results suggest that Cdc2 kinase regulates the nuclear accumulation of cyclin B1 in mouse two-cell embryos.