The giant extracellular hemoglobin (erythrocruorin) from the earth worm (Lumbricus terrestris) has shown promise as a potential hemoglobin-based oxygen carrier (HBOC) in in vivo animal studies. An ...important beneficial characteristic of this hemoglobin (LtHb) is the large number of heme-based oxygen transport sites that helps overcome issues of osmotic stress when attempting to provide enough material for efficient oxygen delivery. A potentially important additional property is the capacity of the HBOC either to generate nitric oxide (NO) or to preserve NO bioactivity to compensate for decreased levels of NO in the circulation. The present study compares the NO-generating and NO bioactivity-preserving capability of LtHb with that of human adult hemoglobin (HbA) through several reactions including the nitrite reductase, reductive nitrosylation, and still controversial nitrite anhydrase reactions. An assignment of a heme-bound dinitrogen trioxide as the stable intermediate associated with the nitrite anhydrase reaction in both LtHb and HbA is supported based on functional and EPR spectroscopic studies. The role of the redox potential as a factor contributing to the NO-generating activity of these two proteins is evaluated. The results show that LtHb undergoes the same reactions as HbA and that the reduced efficacy for these reactions for LtHb relative to HbA is consistent with the much higher redox potential of LtHb. Evidence of functional heterogeneity in LtHb is explained in terms of the large difference in the redox potential of the isolated subunits.
The objective of this study was to determine whether vertebrate-type oestrogens have ecotoxicological effects on a crustacean species. The effects of 17β-oestradiol (E2), diethylstilbestrol (DES), ...bisphenol A (BPA) and 4-nonylphenol (4-NP) on the freshwater invertebrate
Daphnia magna were assessed over first and second generations. The acute EC
50 48
h, based on immobilisation, for E2, DES, BPA and 4-NP were 2.87
mg/l, 1.55
mg/l, 7.75
mg/l and 0.13
mg/l, respectively. The impact of the test chemicals on moulting frequency was also assessed. The EC
50 48
h, based on the inhibition of moult number for E2, DES and 4-NP were 2.04
mg/l, 1.87
mg/l and 0.14
mg/l, respectively. BPA was not observed to impact the moulting frequency of
D. magna at concentrations tested. In a series of separate studies, the effects of the four selected test compounds on the survival, moulting frequency and reproduction of first and second generational
D. magna were assessed over a period of 21
d. Exposure of
D. magna to 4-NP decreased the number of offspring produced in both first and second generation testing. DES proved to have no significant (
p
⩽
0.05) inhibition of fecundity in first generation but when second generation daphnids were exposed to DES, a significant (
p
⩽
0.05) reduction in the number of offspring was recorded. When
D. magna were exposed to E2 or BPA, no statistically significant (
p
⩽
0.05) inhibition in the number of moults or offspring produced was observed.
As the United States population grows more culturally diverse, it is increasingly likely that psychologists will treat patients from dissimilar cultural backgrounds. Psychologists are often undecided ...about whether it is therapeutically appropriate to address cultural differences. Ten clinical considerations regarding the appropriateness of discussing cultural differences with patients are described. Examples are provided of how these suggested guidelines may apply to clinical practice. The literature that has supported addressing differences, including selected theoretical models, is cited in the context of these recommendations. All psychotherapy cases are distinct; therefore, these general guidelines should be adapted to the requirements of the individual patient.
Apelin (APLN) is a recently discovered adipokine involved in the regulation of various metabolic functions. Its receptor, APLNR, is expressed in reproductive tissues, however, its role in human ...ovarian cells is unknown. In this study, we identified APLN and APLNR in human ovarian follicles and analyzed their expression in granulosa cells and follicular fluid obtained from obese and nonobese patients, with or without polycystic ovary syndrome (PCOS). We also investigated the effect of APLN on steroidogenesis in cultured human luteinized granulosa cells (hGCs) from nonobese patients without PCOS. Using RT-PCR and immunoblotting, we found that APLN and APLNR were expressed in hGCs and cumulus and theca cells. We confirmed these data immunohistochemically and observed that APLNR and APLN are present in human oocytes at different stages of follicular development. In patients with PCOS, we observed that follicular fluid APLN concentration and granulosa cell APLN and APLNR mRNA expression was higher than that observed in control patients. In cultured hGCs from nonobese patients without PCOS, insulin-like growth factor 1 (IGF1) increased APLNR expression, and recombinant human APLN (APLN-13 and APLN-17) increased both basal and IGF1-induced steroid secretion. These effects on steroid production were reversed when cultured in the presence of ML221, an APLNR antagonist, which was associated with an increased 3beta-hydrosteroid dehydrogenase (HSD3B) protein concentration. We showed that these effects were dependent on the activation of the AKT and MAPK3/1 pathways using pharmacological inhibitors. Our results show that APLN and APLNR are present in human ovarian cells and APLN increases IGF1-induced steroidogenesis in granulosa cells through an increase in HSD3B protein expression and activation of the MAPK3/1 and Akt pathways. Therefore, APLN and APLNR may play a role in human follicular development and the pathogenesis of PCOS.
It was hypothesized that a reduction in the dietary cation-anion difference (DCAD) before calving, combined with an increase in Ca intake after calving, would reduce the incidence of periparturient ...hypocalcaemia and increase milk production in pasture-based dairy cows. Cows (n = 40) were assigned to one of two DCAD levels before calving (i.e., +7 and +50 mEq/100g). Each group was then assigned to one of two dietary Ca concentrations after calving (i.e., 1.0 and 0.7%) in a 2×2 factorial design. The lower DCAD resulted in a nonrespiratory reduction in systemic pH as indicated by a lower urine pH. This acidosis resulted in an increased concentration of Ca in urine before calving. The lower precalving DCAD helped prevent the decline in blood Ca caused by the onset of lactation, even though blood Ca concentration was lower before calving compared with cows receiving a high DCAD. Supplementation of cows with Ca after calving increased plasma Ca concentration on the day of calving and during the subsequent 14 d. Milk production was not affected by pre- or postcalving treatments.
Context. In 2015, Barman et al. (ApJ, 804, 61) presented detections of absorption from water, carbon monoxide, and methane in the atmosphere of the directly imaged exoplanet HR8799b using integral ...field spectroscopy (IFS) with OSIRIS on the Keck II telescope. We recently devised a new method to analyse IFU data, called molecule mapping, searching for high-frequency signatures of particular molecules in an IFU data cube. Aims. The aim of this paper is to use the molecule mapping technique to search for the previously detected spectral signatures in HR8799b using the same data, allowing a comparison of molecule mapping with previous methods. Methods. The medium-resolution H- and K-band pipeline-reduced archival data were retrieved from the Keck archive facility. Telluric and stellar lines were removed from each spectrum in the data cube, after which the residuals were cross-correlated with model spectra of carbon monoxide, water, and methane. Results. Both carbon monoxide and water are clearly detected at high signal-to-noise, however, methane is not retrieved. Conclusions. Molecule mapping works very well on the OSIRIS data of exoplanet HR8799b. However, it is not evident why methane is detected in the original analysis, but not with the molecule mapping technique. Possible causes could be the presence of telluric residuals, different spectral filtering techniques, or the use of different methane models. We do note that in the original analysis methane was only detected in the K-band, while the H-band methane signal could be expected to be comparably strong. More sensitive observations with the JWST will be capable of confirming or disproving the presence of methane in this planet at high confidence.
The flexible-price two-country monetary model is extended to include a consumption externality with habit persistence. Two methodologies are employed to explore this model's ability to generate ...volatile and persistent exchange rates. In the first, actual data is used for the exogenous driving processes. In the second, the model is simulated using estimated forcing processes. The theory, in both cases, is capable of explaining the high volatility and persistence of real and nominal exchange rates as well as the high correlation between real and nominal rates.
Background: There is evidence that family support can benefit carers of stroke patients, but not the patients themselves. Objective: To extend the follow up of a single blind randomised controlled ...trial of family support for stroke patients and carers to one year to ascertain whether there were any late effects of the intervention. Methods: The study was a randomised controlled trial. Patients admitted to hospital with acute stroke who had a close carer were assigned to receive family support or normal care. Families were visited at home by a researcher 12 months after the stroke, and a series of questionnaires was administered to patient and carer. Results: The benefits to carers mostly persisted, though they were no longer statistically significant because some patients were lost to follow up. There was no evidence of any effects on patients. Conclusion: Family support is effective for carers, but different approaches need to be considered to alleviate the psychosocial problems of stroke patients.
agn43 encodes a major phase-variable outer-membrane protein, antigen 43 (Ag43), involved in autoaggregation of Escherichia coli cells. The gene is present in single copy on the chromosome of E. coli ...K-12. In contrast, Southern hybridization and gene inactivation studies demonstrate that control producer strain E. coli ML308-225 possesses duplicate copies of agn43 (agn43A and agn43B). Construction and analyses of single and double knockout mutants clearly show that both alleles are capable of expressing antigen in a phase-variable manner, with observed differences in the ON<-->OFF switch frequencies appearing to favour expression of Ag43B under conditions of normal laboratory growth. Comparative analysis of agn43A and agn43B gene sequences revealed 98% identity at the nucleotide and predicted protein levels, with differences in the protein sequence of the surface-expressed alpha(43) subunit altering the surface probability of one of the predicted epitopes. Analysis of a panel of enteropathogenic E. coli strains by Southern hybridization using agn43-specific gene probes provided strong evidence for the presence of varying numbers of agn43 alleles within clinical isolates. Taken together, the results indicate the presence of a family of distinct Ag43 proteins encoded by multiple chromosomal alleles.
Panic disorder is a debilitating psychiatric disorder that often co-occurs with substance use disorders. Given the current opioid epidemic, the high reported rates of comorbid panic disorder and ...opioid use disorder are particularly concerning. In this narrative review, we describe the literature on panic disorder and opioid use disorder co-occurrence.
86 studies, 26 reviews, 2 commentaries, and 5 guidelines pertaining to opioid use disorder, panic disorder, and their comorbidity were identified using all EBSCO databases, PubMed, and Google Scholar.
First, we review epidemiological literature on the prevalence of the comorbid condition above and beyond each disorder on its own. Additionally, we discuss the challenges that complicate the differential diagnosis of panic disorder and opioid use disorder and contribute to difficulties establishing rates of comorbidity. Second, we review three theoretical models that have been proposed to explain high rates of co-occurring panic disorder and opioid use disorder: the precipitation hypothesis, the self-medication hypothesis, and the shared vulnerability hypothesis. Third, we outline how co-occurring panic and opioid use disorder may impact treatment for each condition.
Based on findings in the field, we provide recommendations for future research as well as treatment considerations for co-occurring panic and opioid use disorders.