Cortisol is a major osmoregulatory hormone in fishes. Cortisol acts upon the gills, the primary site of ionoregulation, through modifications to specialized ion-transporting cells called ionocytes. ...We tested the hypothesis that cortisol also acts as a major regulator of skin ionocyte remodelling in the amphibious mangrove rivulus (
) when gill function ceases during the water-to-land transition. When out of water,
demonstrated a robust cortisol response, which was linked with the remodelling of skin ionocytes to increase cell cross-sectional area and Na
-K
-ATPase (NKA) content, but not when cortisol synthesis was chemically inhibited by metyrapone. Additionally, we discovered a novel morphology of skin-specific ionocyte that are spikey with multiple cell processes. Spikey ionocytes increased in density, cell cross-sectional area and NKA content during air exposure, but not in metyrapone-treated fish. Our findings demonstrate that skin ionocyte remodelling during the water-to-land transition in amphibious fish is regulated by cortisol, the same hormone that regulates gill ionocyte remodelling in salinity-challenged teleosts, suggesting conserved hormonal function across diverse environmental disturbances and organs in fishes.
Environmental stressors, such as warm temperatures and hypoxia, can interact and pose a threat to aquatic species. Cross talk between the hypoxia and heat stress cellular pathways can lead to ...enhanced cross tolerance between these environmental stressors. In this study, we questioned whether elevated temperatures (from 27° to 32°C) during rearing would enhance the hypoxia-inducible transcription factor-1 (HIF-1)-mediated transcriptional response to hypoxia (5% dissolved O2) in early stages of zebrafish development and whether these differences would be associated with enhanced larval tolerance and survival to hypoxia. We found that embryos reared at 32°C had an enhanced cellular HIF-1 response (elevated hif-1ab and insulin-like growth factor binding-protein mRNA level) and that acute hypoxia (4 h) activated the heat-shock response (elevated hsp70a and hsp90aa mRNA levels). Elevated rearing temperatures and hypoxia exposure also induced precocious hatching, but neither environmental stressor had an effect on the hypoxia tolerance (critical O2 tension) of 4-d-old larvae and did not protect larvae against the lethal effects of a second acute hypoxia exposure. Overall, during early zebrafish development, cross talk between the hypoxia and heat stress cellular pathways at the gene expression level did not confer cross tolerance at the whole-animal level with respect to hypoxia stress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neurovascular alignment is a common anatomical feature of organs, but the mechanisms leading to this arrangement are incompletely understood. Here, we show that vascular endothelial growth factor ...(VEGF) signaling profoundly affects both vascularization and innervation of the pancreatic islet. In mature islets, nerves are closely associated with capillaries, but the islet vascularization process during embryonic organogenesis significantly precedes islet innervation. Although a simple neuronal meshwork interconnects the developing islet clusters as they begin to form at E14.5, the substantial ingrowth of nerve fibers into islets occurs postnatally, when islet vascularization is already complete. Using genetic mouse models, we demonstrate that VEGF regulates islet innervation indirectly through its effects on intra-islet endothelial cells. Our data indicate that formation of a VEGF-directed, intra-islet vascular plexus is required for development of islet innervation, and that VEGF-induced islet hypervascularization leads to increased nerve fiber ingrowth. Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the islet-derived endothelial cell population. We propose a mechanism for coordinated neurovascular development within pancreatic islets, in which endocrine cell-derived VEGF directs the patterning of intra-islet capillaries during embryogenesis, forming a scaffold for the postnatal ingrowth of essential autonomic nerve fibers.
The aim of this study was to assess the prognostic value of a noninvasive measure of left ventricular diastolic pressure (LVDP) early after acute myocardial infarction (MI).
The early diastolic ...velocity of the mitral valve annulus (e′) reflects the rate of myocardial relaxation. When combined with measurement of the early transmitral flow velocity (E), the resultant ratio (E/e′) correlates well with mean LVDP. In particular, an E/e′ ratio >15 is an excellent predictor of an elevated mean LVDP. We hypothesized that an E/e′ ratio >15 would predict poorer survival after acute MI.
Echocardiograms were obtained in 250 unselected patients 1.6 days after admission for MI. Patients were followed for a median of 13 months. The end point was all-cause mortality.
Seventy-three patients (29%) had an E/e′ >15. This was associated with excess mortality (log-rank statistic 21.3, p < 0.0001) and was the most powerful independent predictor of survival (risk ratio 4.8, 95% confidence interval 2.1 to 10.8, p = 0.0002). The addition of E/e′ >15 improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes of left ventricular systolic and diastolic function (p = 0.001).
E/e′ is a powerful predictor of survival after acute MI. An E/e′ ratio >15 is superior, in this respect, to other clinical or echocardiographic features. Furthermore, it provides prognostic information incremental to these parameters.
In fish, vision may be impaired when eye tissue is in direct contact with environmental conditions that limit aerobic ATP production. We hypothesized that the visual acuity of fishes exposed to ...hydrogen sulfide (H
2
S)-rich water would be altered owing to changes in cytochrome c oxidase (COX) activity. Using the H
2
S-tolerant mangrove rivulus (
Kryptolebias marmoratus
), we showed that a 10 min exposure to greater than or equal to 200 µM of H
2
S impaired visual acuity and COX activity in the eye. Visual acuity and COX activity were restored in fish allowed to recover in H
2
S-free water for up to 1 h. Since
K. marmoratus
are found in mangrove pools with H
2
S concentrations exceeding 1000 µM, visual impairment may impact predator avoidance, navigation and foraging behaviour in the wild.
Terrestrial animals must support their bodies against gravity, while aquatic animals are effectively weightless because of buoyant support from water. Given this evolutionary history of minimal ...gravitational loading of fishes in water, it has been hypothesized that weight-responsive musculoskeletal systems evolved during the tetrapod invasion of land and are thus absent in fishes. Amphibious fishes, however, experience increased effective weight when out of water - are these fishes responsive to gravitational loading? Contrary to the tetrapod-origin hypothesis, we found that terrestrial acclimation reversibly increased gill arch stiffness (∼60% increase) in the amphibious fish
when loaded normally by gravity, but not under simulated microgravity. Quantitative proteomics analysis revealed that this change in mechanical properties occurred via increased abundance of proteins responsible for bone mineralization in other fishes as well as in tetrapods. Type X collagen, associated with endochondral bone growth, increased in abundance almost ninefold after terrestrial acclimation. Collagen isoforms known to promote extracellular matrix cross-linking and cause tissue stiffening, such as types IX and XII collagen, also increased in abundance. Finally, more densely packed collagen fibrils in both gill arches and filaments were observed microscopically in terrestrially acclimated fish. Our results demonstrate that the mechanical properties of the fish musculoskeletal system can be fine-tuned in response to changes in effective body weight using biochemical pathways similar to those in mammals, suggesting that weight sensing is an ancestral vertebrate trait rather than a tetrapod innovation.
Effective symptom management is a critical component of cancer treatment. Computational tools that predict the course and severity of these symptoms have the potential to assist oncology clinicians ...to personalize the patient's treatment regimen more efficiently and provide more aggressive and timely interventions. Three common and inter-related symptoms in cancer patients are depression, anxiety, and sleep disturbance. In this paper, we elaborate on the efficiency of Support Vector Regression (SVR) and Non-linear Canonical Correlation Analysis by Neural Networks (n-CCA) to predict the severity of the aforementioned symptoms between two different time points during a cycle of chemotherapy (CTX). Our results demonstrate that these two methods produced equivalent results for all three symptoms. These types of predictive models can be used to identify high risk patients, educate patients about their symptom experience, and improve the timing of pre-emptive and personalized symptom management interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Batterer intervention programs (BIPs) constitute the primary treatment for perpetrators of intimate partner violence (IPV). Systematic evaluations of BIPs, however, have yielded modest results in ...terms of these programs’ ability to reduce perpetration. Descriptive studies, which can provide information on the contexts and process associated with BIPs, can provide insights into the underlying mechanisms that might promote change among BIP clients, and as such are important to improving efficacy measures for BIPs. To date, however, limited research exists on what challenges BIPs encounter in working with clients, and how those challenges present barriers to behavioral change among perpetrators at the intervention level. As part of a 2-year ethnographic study, we conducted 36 individual semistructured interviews with professionals working with BIPs. We identified six themes related to challenges to promoting behavioral change among men who perpetrate violence: (a) social acceptance of IPV, (b) hypermasculine attitudes, (c) emotional problems, (d) childhood exposure to violence, (e) co-morbid mental health issues, and (f) denial, minimization, and blame. Our results have implications for thinking about some of the contextual factors that may impede BIPs ability to produce desired outcomes and for identifying areas in which programs can be tailored to improve the overall client experience. Our results also point to the need for a more coordinated community response to IPV, and in particular to helping provide resources that support BIPs sustained, safe, and as effective as possible work.
Teleost fish have oxygen-sensitive neuroepithelial cells (NECs) in the gills that appear to mediate physiological responses to hypoxia, but little is known about oxygen sensing in amphibious fish. ...The mangrove rivulus, Kryptolebias marmoratus, is an amphibious fish that respires via the gills and/or the skin. First, we hypothesized that both the skin and gills are sites of oxygen sensing in K. marmoratus. Serotonin-positive NECs were abundant in both gills and skin, as determined by immunohistochemical labelling and fluorescence microscopy. NECs retained synaptic vesicles and were found near nerve fibres labelled with the neuronal marker zn-12. Skin NECs were 42% larger than those of the gill, as estimated by measurement of projection area, and 45% greater in number. Moreover, for both skin and gill NECs, NEC area increased significantly (30-60%) following 7 days of exposure to hypoxia (1.5 mg l(-1) dissolved oxygen). Another population of cells containing vesicular acetylcholine transporter (VAChT) proteins were also observed in the skin and gills. The second hypothesis we tested was that K. marmoratus emerse in order to breathe air cutaneously when challenged with severe aquatic hypoxia, and this response will be modulated by neurochemicals associated chemoreceptor activity. Acute exposure to hypoxia induced fish to emerse at 0.2 mg l(-1). When K. marmoratus were pre-exposed to serotonin or acetylcholine, they emersed at a significantly higher concentration of oxygen than untreated fish. Pre-exposure to receptor antagonists (ketanserin and hexamethonium) predictably resulted in fish emersing at a lower concentration of oxygen. Taken together, these results suggest that oxygen sensing occurs at the branchial and/or cutaneous surfaces in K. marmoratus and that serotonin and acetylcholine mediate, in part, the emersion response.
Rhesus (Rh) glycoproteins are ammonia gas (NH(3)) channels known to be involved in ammonia transport in animals. Because of the different osmoregulatory and ionoregulatory challenges faced by teleost ...fishes in marine and freshwater (FW) environments, we hypothesized that ammonia excretion strategies would differ between environments. Also, we hypothesized that cutaneous NH(3) volatilization in air-acclimated fish is facilitated by base secretion. To test these hypotheses, we used the skin of the euryhaline amphibious mangrove rivulus (Kryptolebias marmoratus). The skin excretes ammonia and expresses Rh glycoproteins. Serosal-to-mucosal cutaneous ammonia flux was saturable (0-16 mmol/l ammonia, K(m) of 6.42 mmol/l). In FW, ammonia excretion increased in response to low mucosal pH but decreased with pharmacological inhibition of Na(+)/H(+) exchangers (NHE) and H(+) ATPase. Conversely, in brackish water (BW), lowering the mucosal pH significantly decreased ammonia excretion. Inhibitors of NHE also decreased ammonia excretion in BW fish. Immunofluorescence microscopy demonstrated that both the Rh isoform, Rhcg1, and NHE3 proteins colocalized in Na(+)/K(+) ATPase expressing mitochondrion-rich cells in the gills, kidney, and skin. We propose that the mechanisms of cutaneous ammonia excretion in FW K. marmoratus are consistent with the model for branchial ammonia excretion in FW teleost fish. NH(4)(+) excretion appeared to play a stronger role in BW. NH(4)(+) excretion in BW may be facilitated by apical NHE and/or diffuse through paracellular pathways. In aerially acclimated fish, inhibition of NHE and H(+) ATPase, but not the Cl(-)/HCO(3)(-) exchanger, significantly affected cutaneous surface pH, suggesting that direct base excretion is not critical for NH(3) volatilization. Overall, K. marmoratus use different strategies for excreting ammonia in three different environments, FW, BW, and air, and Rh glycoproteins and NHE are integral to all.
PDF
