123 research outputs found
Dietary ω-3 fatty acid supplementation improves murine sickle cell bone disease and reprograms adipogenesis
Sickle cell disease (SCD) is a genetic disorder of hemoglobin, leading to chronic hemolytic anemia and multiple organ damage. Among chronic organ complications, sickle cell bone disease (SBD) has a very high prevalence, resulting in long-term disability, chronic pain and fractures. Here, we evaluated the effects of ω-3 (fish oil-based, FD)-enriched diet vs. ω-6 (soybean oil-based, SD)-supplementation on murine SBD. We exposed SCD mice to recurrent hypoxia/reoxygenation (rec H/R), a consolidated model for SBD. In rec H/R SS mice, FD improves osteoblastogenesis/osteogenic activity by downregulating osteoclast activity via miR205 down-modulation and reduces both systemic and local inflammation. We also evaluated adipogenesis in both AA and SS mice fed with either SD or FD and exposed to rec H/R. FD reduced and reprogramed adipogenesis from white to brown adipocyte tissue (BAT) in bone compartments. This was supported by increased expression of uncoupling protein 1(UCP1), a BAT marker, and up-regulation of miR455, which promotes browning of white adipose tissue. Our findings provide new insights on the mechanism of action of ω-3 fatty acid supplementation on the pathogenesis of SBD and strengthen the rationale for ω-3 fatty acid dietary supplementation in SCD as a complementary therapeutic intervention
Development and evaluation of a web-based breast cancer cultural competency course for primary healthcare providers
<p>Abstract</p> <p>Background</p> <p>To develop and evaluate a continuing medical education (CME) course aimed at improving healthcare provider knowledge about breast cancer health disparities and the importance of cross-cultural communication in provider-patient interactions about breast cancer screening.</p> <p>Methods</p> <p>An interactive web-based CME course was developed and contained information about breast cancer disparities, the role of culture in healthcare decision making, and demonstrated a model of cross-cultural communication. A single group pre-/post-test design was used to assess knowledge changes. Data on user satisfaction was also collected.</p> <p>Results</p> <p>In all, 132 participants registered for the CME with 103 completing both assessments. Differences between pre-/post-test show a significant increase in knowledge (70% vs. 94%; p < .001). Ninety-five percent of participants agreed that the web based training was an appropriate tool to train healthcare providers about cultural competency and health disparities.</p> <p>Conclusion</p> <p>There was an overall high level of satisfaction among all users. Users felt that learning objectives were met and the web-based format was appropriate and easy to use and suggests that web-based CME formats are an appropriate tool to teach cultural competency skills. However, more information is needed to understand how the CME impacted practice behaviors.</p
Search for a new gauge boson in the Experiment (APEX)
We present a search at Jefferson Laboratory for new forces mediated by
sub-GeV vector bosons with weak coupling to electrons. Such a
particle can be produced in electron-nucleus fixed-target scattering and
then decay to an pair, producing a narrow resonance in the QED trident
spectrum. Using APEX test run data, we searched in the mass range 175--250 MeV,
found no evidence for an reaction, and set an upper limit of
. Our findings demonstrate that fixed-target
searches can explore a new, wide, and important range of masses and couplings
for sub-GeV forces.Comment: 5 pages, 5 figures, references adde
Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis
OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts.
METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured.
RESULTS: In participants with heterozygous SOD1
INTERPRETATION: These results highlight the ability of stable isotope labeling approaches and peptide deamidation to discern the influence of disease mutations on protein kinetics and stability and support implementation of this method to optimize clinical trial design of gene and molecular therapies for neurological disorders.
TRIAL REGISTRATION: Clinicaltrials.gov: NCT03449212
Trypanosoma (Herpetosoma) rangeli Tejera, 1920: intracellular amastigote stages of reproduction in white mice
Electroexcitation of the at low momentum transfer
We report on new p measurements at the
resonance at the low momentum transfer region. The mesonic
cloud dynamics is predicted to be dominant and rapidly changing in this
kinematic region offering a test bed for chiral effective field theory
calculations. The new data explore the low dependence of the resonant
quadrupole amplitudes while extending the measurements of the Coulomb
quadrupole amplitude to the lowest momentum transfer ever reached. The results
disagree with predictions of constituent quark models and are in reasonable
agreement with dynamical calculations that include pion cloud effects, chiral
effective field theory and lattice calculations. The reported measurements
suggest that improvement is required to the theoretical calculations and
provide valuable input that will allow their refinements
Genetic diversity and phylogenetic relationships of coevolving symbiont-harboring insect trypanosomatids, and their neotropical dispersal by invader African blowflies (Calliphoridae)
This study is about the inter- and intra-specific genetic diversity of trypanosomatids of
the genus Angomonas, and their association with Calliphoridae (blowflies) in Neotropical
and Afrotropical regions. Microscopic examination of 3,900 flies of various families,
mostly Calliphoridae, revealed that 31% of them harbored trypanosomatids. Small
subunit rRNA (SSU rRNA) barcoding showed that Angomonas predominated (46%)
over the other common trypanosomatids of blowflies of genera Herpetomonas and
Wallacemonas. Among Angomonas spp., A. deanei was much more common than
the two-other species, A. desouzai and A. ambiguus. Phylogenetic analyses based
on SSU rRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH)
and internal transcribed spacer rDNA (ITS rDNA) sequences revealed a marked
genetic diversity within A. deanei, which comprised four infraspecific genotypes (Dea1–
Dea4), and four corresponding symbiont genotypes (Kcr1–Kcr4). Host and symbiont
phylogenies were highly congruent corroborating their co-divergence, consistent with
host-symbiont interdependent metabolism and symbiont reduced genomes shaped by
a long coevolutionary history. We compared the diversity of Angomonas/symbionts from
three genera of blowflies, Lucilia, Chrysomya and Cochliomyia. A. deanei, A. desouzai,
and A. ambiguus were found in the three genera of blowflies in South America. In Africa,
A. deanei and A. ambiguus were identified in Chrysomya. The absence of A. desouzai
in Africa and its presence in Neotropical Cochliomyia and Lucilia suggests parasite
spillback of A. desouzai into Chrysomya, which was most likely introduced four decades
ago from Africa into the Neotropic. The absence of correlation between parasite diversity
and geographic and genetic distances, with identical genotypes of A. deanei found in the Neotropic and Afrotropic, is consistent with disjunct distribution due to the recent
human-mediated transoceanic dispersal of Angomonas by Chrysomya. This study
provides the most comprehensive data gathered so far on the genetic repertoires of
a genus of trypanosomatids found in flies from a wide geographical range.The PROAFRICA, INCT-EPIAMO,
and PROSUL programs of CNPq, PNIPB of Capes, and FAPESP
(Process 2016/07487-0). CAPEs (PNPD) granted a postdoctoral
scholarship to TB.http://www.frontiersin.org/Microbiologyam2018Veterinary Tropical Disease
Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli
Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts. Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins. Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets
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Multiphase phenomena in Diesel fuel injection systems
Fuel Injection Equipment (FIE) are an integral component of modern Internal Combustion Engines (ICE), since they play a crucial role in the fuel atomization process and in the formation of a fuel/air combustible mixture, consequently affecting efficiency and pollutant formation. Advancements and improvements of FIE systems are determined by the complexity of the physical mechanisms taking place; the spatial scales are in the order of millimetres, flow may become locally highly supersonic, leading to very small temporal scales of microseconds or less. The operation of these devices is highly unsteady, involving moving geometries such as needle valves. Additionally, extreme pressure changes imply that many assumptions of traditional fluid mechanics, such as incompressibility, are no longer valid. Furthermore, the description of the fuel properties becomes an issue, since fuel databases are scarce or limited to pure components, whereas actual fuels are commonly hydrocarbon mixtures. Last but not least, complicated phenomena such as phase change or transition from subcritical to transcritical/supercritical state of matter further pose complications in the understanding of the operation of these devices
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