RNA-dependent RNA polymerases (RdRp) are very ancient enzymes and are essential for all viruses with RNA genomes. We reconstruct the origin and evolution of this polymerase since the initial stages ...of the origin of life. The origin of the RdRp was traced back from tRNA ancestors. At the origin of the RdRp the most ancient part of the protein is the cofactor-binding site that had the capacity of binding to simple molecules as magnesium, calcium, and ribonucleotides. Our results suggest that RdRp originated from junctions of proto-tRNAs that worked as the first genes at the emergence of the primitive translation system, where the RNA was the informational molecule. The initial domain, worked as a building block for the emergence of the fingers and thumb domains. From the ancestral RdRp, we could establish the evolutionary stages of viral evolution from a rooted ancestor to modern viruses. It was observed that the selective pressure under the RdRp was the organization and functioning of the genome, where RNA double-stranded and RNA single-stranded virus formed a separate group. We propose an evolutionary route to the polymerases and the results suggest an ancient scenario for the origin of RNA viruses.
Systematic review of pelvic floor interventions during pregnancy Schreiner, Lucas; Crivelatti, Isabel; Oliveira, Julia M. ...
International journal of gynecology and obstetrics,
October 2018, 2018-Oct, 2018-10-00, 20181001, Letnik:
143, Številka:
1
Journal Article
Recenzirano
Background
Pelvic floor interventions during pregnancy could reduce the impact of pregnancy and delivery on the pelvic floor.
Objective
To determine the effects of pelvic floor interventions during ...pregnancy on childbirth‐related and pelvic floor parameters.
Search strategy
PubMed, Embase, and LILACS were searched for reports published during between 1990 and 2016 in English, Spanish, or Portuguese. The search terms were “pregnancy,” “pelvic floor muscle training,” and related terms.
Selection criteria
Randomized controlled trials with healthy pregnant women were included.
Data collection and analysis
Baseline and outcome data (childbirth‐related parameters, pelvic floor symptoms) were compared for three interventions: EPI‐NO (Tecsana, Munich, Germany) perineal dilator, pelvic floor muscle training, and perineal massage.
Main results
A total of 22 trials were included. Two of three papers assessing EPI‐NO showed no benefit. The largest study investigating pelvic floor muscle training reported a significant reduction in the duration of the second stage of labor (P<0.01), and this intervention also reduced the incidence of urinary incontinence (evaluated in 10 trials). Two of six trials investigating perineal massage reported that a lower rate of perineal pain was associated with this intervention.
Conclusion
Pelvic floor muscle training and perineal massage improved childbirth‐related parameters and pelvic floor symptoms, whereas EPI‐NO showed no benefit.
Pelvic floor muscle training during pregnancy shortens the second stage of labor and reduces urinary incontinence, whereas perineal massage reduces perineal pain.
This article includes a Portuguese translation of the , available in the Supporting Information section.
► Atrazine effects were assessed in fish using biochemical and genetic biomarkers. ► Atrazine promoted a decreasing trend on biotransformation and antioxidant enzymes. ► DNA damage was observed in ...different cell types of fish exposed to atrazine. ► Atrazine did not increase ROS generation and LPO in the liver. ► Atrazine did not promote changes in muscle or brain AChE.
The effects of Atrazine, an herbicide used worldwide and considered as a potential contaminant in aquatic environments, were assessed on the Neotropical fish Prochilodus lineatus acutely (24 and 48h) exposed to 2 or 10μgL−1 of atrazine by using a set of biochemical and genetic biomarkers. The following parameters were measured in the liver: activity of the biotransformation enzymes ethoxyresorufin-O-deethylase (EROD) and glutathione S transferase (GST), antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), content of reduced glutathione (GSH), generation of reactive oxygen species (ROS) and occurrence of lipid peroxidation (LPO); in brain and muscle the activity of acetylcholinesterase (AChE) and DNA damage (comet assay) on erythrocytes, gills and liver cells. A general decreasing trend on the biotransformation and antioxidant enzymes was observed in the liver of P. lineatus exposed to atrazine; except for GR, all the other antioxidant enzymes (SOD, CAT and GPx) and biotransformation enzymes (EROD and GST) showed inhibited activity. Changes in muscle or brain AChE were not detected. DNA damage was observed in the different cell types of fish exposed to the herbicide, and it was probably not from oxidative origin, since no increase in ROS generation and LPO was detected in the liver. These results show that atrazine behaves as enzyme inhibitor, impairing hepatic metabolism, and produces genotoxic damage to different cell types of P. lineatus.
Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of the fetus' full growth potential and occurs in a natural and severe manner in pigs as a result of ...placental insufficiency. Reduced skeletal muscle mass in the fetus with IUGR persists into adulthood and may contribute to increased metabolic disease risk. To investigate skeletal muscle postnatal development, histomorphometrical patterns of the semitendinosus muscle, myosin heavy chain (MyHC; embryonic I, IIA, IIB and IIX isoforms) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100 days old), hypertrophy (100–150 days old), and postnatal development (newborn to 150 days old) were evaluated in female pigs with IUGR and normal birth weight (NW) female littermates. NW females presented higher body weights compared to their IUGR counterparts at all ages evaluated (P < 0.05). Moreover, growth restriction in utero affected the semitendinosus muscle weight, muscle fiber diameter, and muscle cross‐sectional area, which were smaller in IUGR pigs at birth (P < 0.05). Notwithstanding the effects on muscle morphology, IUGR also affected muscle fiber composition, as the percentage of MyHC‐I myofibers was higher at birth (P < 0.05), and, in 150‐day‐old gilts, a lower percentage of MyHC‐IIX isoform (P < 0.05) and the presence of embryonic MyHC isoform were also observed. Regarding the pattern of gene expression in both the postnatal myogenesis and postnatal development periods, IUGR led to the downregulation of myogenic factors, which delayed skeletal muscle myogenesis (PAX7, MYOD, MYOG, MYF5 and DES). Altogether, growth restriction in utero affects muscle fiber number and size at birth and muscle fiber composition through the downregulation of myogenic factors, which determines the individual´s postnatal growth rate. This fact, associated with delayed myofiber development in growth‐restricted animals, may affect meat quality characteristics in animal production. Hence, knowledge of the morphofunctional phenotype of the skeletal muscle throughout postnatal development in individuals with IUGR, and the mechanism that governs it, may provide a better understanding of the mechanisms that limit postnatal muscle growth, and help the establishment of potential strategies to improve muscle development and prevent the onset of later‐life metabolic diseases.
In the present study, the morphofunctional aspects of skeletal muscle were evaluated during postnatal development in pigs with intrauterine growth restriction. The presence of embryonic myosin heavy chain protein isoform in adulthood and the downregulation of myogenic genes in the skeletal muscle were described for the first time.
Abstract
Background Although there are several ways to assess pain in dementia, there is still a need for tools with better items to assess the presence of pain intensity in these individuals.
...Objective To validate to Brazilian version of the “Pain Intensity Measure for Persons with Dementia – PIMD-p.
Methods Older adults, all demented with impaired verbal communication and exposed to potentially painful situations, were selected from an outpatient clinic and long-term care facility (LTCF). The PIMD-p was applied independently by 2 researchers (E1 and E2) on the same day. Within 14 days, the instrument was reapplied by one of the 2 researchers (E3). The pain intensity reported by participants' caregivers and LTCF nurses were recorded on a verbal numeric pain scale. For the statistical analysis, Cronbach's Alpha, Spearman's Coefficient and intraclass correlation Index were calculated.
Results A total of 50 older individuals were selected (mean age 86 years), majority with musculoskeletal pain. The PIMD-p demonstrated good internal consistency according to Cronbach's α (0.838), excellent intra and interobserver reproducibility (0.927 and 0.970, respectively; p < 0.001), and convergent validity (strong significant correlations between reported pain intensities and pain indicators on the PIMD-p (except for expressive eyes; corr = 0.106 and p = 0.462). A ROC curve was plotted to determine the best cut-off for the PIMD-P, and a score of 7.5 predicted moderate-to-severe pain, with 77.8% sensitivity and 95.7% specificity (p < 0.001).
Conclusion The PIMD-p showed satisfactory psychometric properties for measuring intensity of pain in demented older adults with impaired verbal communication.
The survival of several fish species in captivity depends on their adaptation to the environmental conditions and the biological characteristics. The objective of the study was to evaluate the ...influence of different light intensity levels in growth, behavior and skin pigmentation in juvenile of Lophiosilurus alexandri. Fishes were exposed to the following luminosities: 0, 218, 278, and 459 lux. The experiment was conducted for 75 days, in a water recirculation system with controlled temperatures and aeration. Catfish juvenile were distributed in 35 L aquariums, at the density of 0.28 ind L.sup.-1. In order to evaluate fish growth, weight, standardtotal length, weight gain, food consumption, food conversion, biomass, specific growth rate and survival were measured twice times a month. Also, swimming behavior, skin pigmentation and plasma cortisol levels were evaluated. Light influences L. alexandri feed consumption, food conversion, behavior and plasma cortisol levels. Environments with low light are recommended for the L. alexandri growth.
•Juveniles of P. lineatus were exposed to caffeine (CAF) for 24 h or 168 h.•After 168 h of CAF exposure EROD activity increased in liver and decreased in brain.•CAF did not promote lipoperoxidation ...in liver and brain.•CAF did not promote DNA damage in blood cells.•CAF interfered on biotransformation but did not cause a state of oxidative stress.
Caffeine is often found in aquatic environments, leading to concerns regarding its adverse consequences for aquatic biota. Biochemical and genotoxic biomarkers were analysed in juveniles of Prochilodus lineatus to evaluate the effects of caffeine. Fish were exposed to caffeine (0.3, 3 and 30 μg L−1) for either 24 h or 168 h. Longer exposure to caffeine resulted in a significant reduction in the activity of the phase I biotransformation enzyme ethoxyresorufin-O-deethylase (EROD) in the brain but a significant increase in the liver. Changes in glutathione content (GSH), glutathione S-transferase (GST) activity, and lipid peroxidation were not found in the liver and brain of fish exposed to caffeine. DNA damage in erythrocytes were also not found. These results show that caffeine may interfere with the biotransformation mechanism of P. lineatus after 168 h exposure, but it does not generate sufficient changes to trigger a state of oxidative stress.
A novel series of furoxan (1,2,5-oxadiazole 2-oxide) (compounds 3, 4a and -b, 13a and -b, and 14a to -f) and benzofuroxan (benzoc1,2,5oxadiazole 1-oxide) (compounds 7 and 8a to -c) derivatives were ...synthesized, characterized, and evaluated for in vitro activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. The furoxan derivatives exhibited the ability to generate nitric oxide at different levels (7.8% to 27.4%). The benzofuroxan derivative 8a was able to increase nitrite production in medium supernatant from murine macrophages infected with L. amazonensis at 0.75 mM after 48 h. Furoxan and benzofuroxan derivatives showed remarkable leishmanicidal activity against both promastigote and intracellular amastigote forms. Compounds 8a, 14a and -b, and 14d exerted selective leishmanicidal activities superior to those of amphotericin B and pentamidine. In vitro studies at pH 5.4 reveal that compound 8a is stable until 8 h and that compound 14a behaves as a prodrug, releasing the active aldehyde 13a. These compounds have emerged as promising novel drug candidates for the treatment of leishmaniasis.
Zika virus (ZIKV) is a mosquito-borne virus that is phylogenetically close to other medically important flaviviruses with high global public health significance, such as dengue (DENV) and yellow ...fever (YFV) viruses. Correct diagnosis of a flavivirus infection can be challenging, particularly in world regions where more than one flavivirus co-circulates and YFV vaccination is mandatory. Acid nucleic aptamers are oligonucleotides that bind to a specific target molecule with high affinity and specificity. Because of their unique characteristics, aptamers are promising tools for biosensor development. Aptamers are usually obtained through a procedure called “systematic evolution of ligands by exponential enrichment” (SELEX). In this study, we select an aptamer (termed ZIKV60) by capillary electrophoresis SELEX (CE-SELEX) to the Zika virus non-structural protein 1 (NS1) and counterselection against the NS1 proteins of DENV (serotypes 1, 2, 3, and 4) and YFV. The ZIKV60 dissociation constant (
K
d
) is determined by enzyme-linked oligonucleotide assay (ELONA) and the aptamer specificity is evaluated by quantitative real-time polymerase chain reaction. ZIKV60 shows a high binding affinity to the ZIKV NS1 protein with a
K
d
value of 2.28 ± 0.28 nM. The aptamer presents high specificity for ZIKV NS1 compared to NS1 of DENV and YFV. Furthermore, graphene field-effect transistor devices functionalized with ZIKV60 exhibit an evident identification of NS1 protein diluted in human serum. These results point to the applicability of biosensors based on the ZIKV60 aptamer for the differential diagnosis of the Zika virus.
Display omitted
The enzyme glycerol-3-phosphate dehydrogenase (G3PDH) from Leishmania species is considered as an attractive target to design new antileishmanial drugs and a previous in silico study ...reported on the importance of chalcones to achieve its inhibition. Here, we report the identification of a synthetic chalcone in our in vitro assays with promastigote cells from Leishmania amazonensis, its biological activity in animal models, and docking followed by molecular dynamics simulation to investigate the molecular interactions and structural patterns that are crucial to achieve the inhibition complex between this compound and G3PDH. A molecular fragment of this natural product derivative can provide new inhibitors with increased potency and selectivity.
PDF
