Hearing Aid Amplification Improves Postural Control for Older Adults With Hearing Loss When Other Sensory Cues Are Impoverished.

Recent studies suggest that sound amplification via hearing aids can improve postural control in adults with hearing impairments. Unfortunately, only a few studies used well-defined posturography measures to assess balance in adults with hearing loss with and without their hearing aids. Of these, only two examined postural control specifically in the elderly with hearing loss. The present study examined the impact of hearing aid use on postural control during various sensory perturbations in older adults with age-related hearing loss. Thirty individuals with age-related hearing impairments and using hearing aids bilaterally were tested. Participants were asked to perform a modified clinical sensory integration in balance test on a force platform with and without hearing aids. The experiment was conducted in the presence of a broadband noise ranging from 0.1 to 4 kHz presented through a loudspeaker. As expected, hearing aid use had a beneficial impact on postural control, but only when visual and somatosensory inputs were both reduced. Data also suggest that hearing aid use decreases the dependence on somatosensory input for maintaining postural control. This finding can be of particular importance in older adults considering the reduction of tactile and proprioceptive sensitivity and acuity often associated with aging. These results provide an additional argument for encouraging early hearing aid fitting for people with hearing loss.

Exposure to Contaminated River Water is Associated with Early Hatching and Dysregulation of Gene Expression in Early Life Stages of the Endangered Copper Redhorse (Moxostoma hubbsi).

The copper redhorse (Moxostoma hubbsi) is an endangered fish that spawns exclusively in the Richelieu River (Quebec, Canada). Tributaries of the Richelieu are contaminated with high levels of current-use pesticides, which may impact early-life stage (ELS) copper redhorse and other native fishes. We assessed the effects of exposure to contaminated river water on ELS copper redhorse and river redhorse (Moxostoma carinatum), a related fish that shares the copper redhorse's spawning grounds and nursery habitat. A riverside flow-through system was used to expose copper and river redhorse embryos (1000 each) to Richelieu River water or laboratory water as a control. Fish were maintained until 14 days posthatch, and water samples were taken daily for chemical analysis. Following a heavy rain event, concentrations of two neonicotinoid pesticides, clothianidin and thiamethoxam, exceeded water quality guidelines for aquatic life (20 ng/L). Using nontargeted screening, we tentatively identified an additional 24 pharmaceutical and personal care products and 23 pesticides in river water. Effects of river water on ELS fish were observed in both species, but the copper redhorse appeared to be more sensitive. Fish exposed to river water hatched 10.7 (copper redhorse) and 2.4 (river redhorse) cumulative degree days earlier than controls. Copper redhorse survival was significantly lower in river water (73 ± 16%) compared to laboratory water (93 ± 3%), whereas river redhorse survival was similar between treatments (84 ± 6% and 89 ± 4%, respectively). Sequencing of copper redhorse larvae RNA revealed 18 differentially expressed genes (DEGs) following 14 days of exposure to river water. Eight up-regulated DEGs were linked to immune function and injury response, and seven down-regulated DEGs were involved with digestion and nutrient absorption. The present study provided valuable data on the effects of ELS exposure to a real-world mixture of contaminants in two fish species of concern. Environ Toxicol Chem 2022;41:1950-1966. © 2022 SETAC.

Biological markers to establish a relationship between the health status of the St. Lawrence River yellow perch (Perca flavescens) with a gradient of anthropogenic disturbances.

Since the mid-1990s, the decline of the yellow perch population of Lake Saint-Pierre (hereinafter LSP) in Quebec, Canada has been the subject of several research programs. The combined effect of habitat deterioration, the presence of invasive species, and poor water quality negatively affected the yellow perch population in this lake. In 2013, we sampled yellow perch (larvae, juveniles and adults) at six sites along the St. Lawrence River representing a gradient of increasing human influences from upstream to downstream and measured several biomarkers including retinoid compounds (vitamin A). In the most contaminated sites (LSP, north and south shores), we found that retinoid stores were decreased in all three stages of development. To corroborate these results and to test other biomarkers, we once again sampled yellow perch (adults only) from the same sites. Results from our 2014 and 2015 samplings confirmed that LSP yellow perch appeared to be at a disadvantage compared to fish from upstream populations. Individuals from LSP have lower acetylcholinesterase (AChE) activity as well as lower retinoid levels in liver and plasma. These fish were also marked by lower levels of antioxidants such as lycopene and vitamin E. A discriminant analysis of this set of results confirmed that the yellow perch of the LSP could be easily discriminated from those of the other sites (2014 and 2015) on the basis of liver retinoid and, to a lesser extent, of the liver tocopherol and protein concentration of the muscle, as well as AChE activity and DROH (all-trans-3,4-dehydroretinol) measured in plasma.

A major release of urban untreated wastewaters in the St. Lawrence River (Quebec, Canada) altered growth, reproduction, and redox status in experimentally exposed Daphnia magna.

In 2015, five billion liters of untreated urban wastewater (UWW) were released into the St. Lawrence River (Quebec, Canada) over the course of four days in order to repair the Montreal's sewer interceptor network related to the city's primary wastewater treatment plant. The UWW discharge originated mainly from household, industrial, and hospital sources. The objective of this study was to investigate the toxicological effects of this unprecedented punctual UWW release on aquatic invertebrates to gather information that could help understand the potential impacts to the receiving environment of overflow episodes occurring during heavy rain events. Water samples were collected at four impacted and non-impacted sites during and four weeks after the release. The freshwater crustacean Daphnia magna were experimentally exposed to surface water collected from UWW-impacted sites for 13 days and analyzed for life-history endpoints and suitable biomarkers related to oxidative stress (i.e., catalase, superoxide dismutase, lipid peroxidation, and glutathione-s-transferase) and reproduction (chitinase). Results indicated that D. magna growth and reproduction were significantly increased by exposure to UWWs. These effects were correlated with an increase in chitinase activity, which is primarily controlled by reproductive hormones and involved in growth, suggesting potential impacts on these processes. Results also indicated that some UWW samples might have caused oxidative stress during the release but that it was overcome by antioxidant defenses and did not lead to cellular damage. Overall, current results contribute to a better understanding of the biological impacts of UWW to aquatic invertebrates for a better stormwater management.

Vestibular Function Modulates the Benefit of Hearing Aids in People With Hearing Loss During Static Postural Control.

OBJECTIVES: To evaluate the influence of auditory cues on postural sway in normal-hearing (NH) individuals, hearing-impaired individuals with vestibular impairment (HIVL), or hearing-impaired (HI) individuals without vestibular impairment. DESIGN: Thirty-two participants received a hearing and a vestibular evaluation (vHIT, oVEMP, cVEMP) and then were separated in to three groups (NH, HI, HIVL). All participants had to stand on a force platform in four postural conditions (A: EO/firm, B: EC/firm, C: EO/Foam, D: EC/Foam) under two auditory conditions, with or without auditory cues. RESULTS: Results revealed that first, there was a significant difference between HIVL and both HI and NH groups in conditions C and D without auditory cues. Second, greater improvement for HIVL compared to NH and HI groups in condition C and D was observed with auditory cues. Finally, somatosensory reliance significantly decreased for the HIVL participants using hearing aids compared to NH and HI. CONCLUSIONS: Our results suggest that hearing aids benefit for postural control may be modulated by vestibular function.

Trends of persistent organic pollutants in ringed seals (Phoca hispida) from the Canadian Arctic.

Ringed seals (Phoca hispida) have been used as bioindicator species of environmental contamination in Canada since the 1970s. In the present study, seals were harvested during subsistence hunts in four regions of the Canadian Arctic: Beaufort Sea, Arctic Archipelago, Hudson Bay, and coastal Labrador. An extensive suite of persistent organic pollutants (POPs) was determined in seal blubber collected for multiple years between 1972 and 2016. Results from this long-term study indicate geographical differences in the contaminant concentrations in seals and the significant general decrease of most POPs, including polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and related compounds, chlordanes (CHL), and hexachlorocyclohexanes (HCH) over time in ringed seals. The highest decrease rates (up to -9.1%/year for α-HCH) were found in seals from the Hudson Bay region where all chemicals investigated have significantly decreased since 1986. Significant increases in concentrations of hexachlorobenzene (HCB) in seals from Labrador and ß-HCH in Sachs Harbour, NT and Arctic Archipelago were observed. Site-specific and contaminant-specific associations between climate pattern (i.e., Arctic Oscillation, North Atlantic Oscillation, and Pacific/North American pattern) and mean ice-coverage (total, first-year ice, and old-ice) were found at sites with the longest time trend data (i.e., Arviat, Sachs Harbour/Ulukhaktok and Resolute Bay). Overall, results suggest that North American and international regulations have led to the long-term reduction of most POPs in Canadian Arctic ringed seals by reducing emissions from primary sources. However, other sources of legacy compounds (e.g., environmental reservoirs) as well changes in food web composition and structure in relation to climate changes could also be influencing the very slow rates of decline, or stable levels, of contaminants found in seals at some sites. Further work is warranted to discern between co-variation of climate changes and contaminant concentrations and cause-and-effect relationships.

Improved tactile frequency discrimination in musicians.

Music practice is a multisensory training that is of great interest to neuroscientists because of its implications for neural plasticity. Music-related modulation of sensory systems has been observed in neuroimaging data, and has been supported by results in behavioral tasks. Some studies have shown that musicians react faster than non-musicians to visual, tactile and auditory stimuli. Behavioral enhancement in more complex tasks has received considerably less attention in musicians. This study aims to investigate unisensory and multisensory discrimination capabilities in musicians. More specifically, the goal of this study is to examine auditory, tactile and auditory-tactile discrimination in musicians. The literature suggesting better auditory and auditory-tactile discrimination in musicians is scarce, and no study to date has examined pure tactile discrimination capabilities in musicians. A two-alternative forced-choice frequency discrimination task was used in this experiment. The task was inspired by musical production, and participants were asked to identify whether a frequency was the same as or different than a standard stimulus of 160 Hz in three conditions: auditory only, auditory-tactile only and tactile only. Three waveforms were used to replicate the variability of pitch that can be found in music. Stimuli were presented through headphones for auditory stimulation and a glove with haptic audio exciters for tactile stimulation. Results suggest that musicians have lower discrimination thresholds than non-musicians for auditory-only and auditory-tactile conditions for all waveforms. The results also revealed that musicians have lower discrimination thresholds than non-musicians in the tactile condition for sine and square waveforms. Taken together, these results support the hypothesis that musical training can lead to better unisensory tactile discrimination which is in itself a new and major finding.

Determination of the bioavailability of selected pharmaceutical residues in fish plasma using liquid chromatography coupled to tandem mass spectrometry.

Aquatic systems near major urban centers are constantly contaminated with effluent from wastewater treatment plants. Pharmaceuticals are part of the contamination and several classes of drugs have been detected in surface waters in the last decade. To better understand the impact of those pharmaceuticals in ecosystems, the exposure to aquatic species needs to be investigated. This study presents a new simple and rugged quantitative method for the determination of several classes of drugs using 100µL of plasma from fish environmentally exposed to a major but highly diluted urban effluent. Six common drugs (i.e., diclofenac, ibuprofen, naproxen, salbutamol, sulfamethoxazole and trimethoprim) and one major metabolite (2-hydroxy-ibuprofen), present in significant amount in impacted waterways have been selected for the development and validation of the method. First, all drugs were extracted using cation exchange solid phase extraction (SPE) and eluted with two solvent mixtures. Then, the extracts were analyzed using a reverse-phase analytical column Waters® CORTECS C18+ (150×2.1mm, 2.7µm) within 14min. MS/MS was performed with an electrospray (ESI) interface in positive ion mode, with multiple reaction monitoring (MRM) experiment acquiring two product ions per drugs. Quantification has been made with standard curves for each analyte using isotopically labeled internal standards. This method has high sensitivity with limits of quantification of 1ngmL-1 for each drug, except for ibuprofen and its metabolite 2-hydroxy-ibuprofen at 2ngmL-1. The precision of the method was below 11%, the accuracy between 94 and 105% and overall recovery between 94 and 111% for all drugs, with high selectivity. Application of the method to plasma samples from wild northern pike inhabiting the St. Lawrence River collected over a three-year period showed the presence of naproxen, diclofenac, trimethoprim and salbutamol at very low concentrations (around 1ngmL-1).

Inhibition of platelet aggregation ex vivo is repressed in apolipoprotein E deficient mice.

In the present study, we assessed whether the endogenous platelet inhibitory mechanisms are altered in the early to moderate stages of the atherosclerotic process. Apolipoprotein E deficient mice (ApoE-/-), a mouse model of atherosclerosis, and their wild-type (WT) counterparts were used to assess agonist-stimulated synthesis of prostacyclin (PGI2), inhibition of platelet aggregation ex vivo, and intra-platelet cAMP levels. Basal U46619 and ADP -induced platelet aggregation in vitro were increased in ApoE-/- mice at 18-20 weeks in comparison with 8-10 weeks of age. Systemically administered endothelin-1 (ET-1) or bradykinin (BK) inhibited platelet aggregation in a similar fashion in 8- to 10-week-old ApoE-/- and WT mice, but not in the ApoE-/- mice at 18-20 weeks of age, although both peptides maintained their capacity to increase plasma levels of the PGI2. Intravenous infusion of PGI2 also failed to inhibit platelet aggregation ex vivo in 18- to 20-week-old ApoE-/- mice. Interestingly, both BK and PGI2 retained their ability to increase intraplatelet cAMP in WT and ApoE-/- mice. Our results suggest that a loss of activity of endogenous inhibitorymechanisms could contribute to the increased platelet reactivity in ApoE-/- mice, and that this phenomenon occurs early in the intermediate stage of the atherosclerotic process.

Spatial and temporal trends of alternative flame retardants and polybrominated diphenyl ethers in ringed seals (Phoca hispida) across the Canadian Arctic.

Concentrations of alternative flame retardants and polybrominated diphenyl ethers (PBDEs) were analyzed in ringed seal (Phoca hispida) blubber collected across the Canadian Arctic during subsistence hunts between 1998 and 2013. More than 80% of sampled animals were females and juvenile males. The highest mean ΣPBDE concentrations (sum of 13 congeners) were found in seals from Nain (Nunatsiavut) as well as Inukjuaq and Arviat (Hudson Bay) and the lowest mean levels were found in seals from Lancaster Sound. BDE-47 and -99 were the predominant PBDE congeners quantified in ringed seals. The most frequently detected non-PBDE flame retardants were polybrominated biphenyl 101 (BB-101, 57% of samples analyzed for this chemical), hexabromocyclododecane (HBCDD; 38%), hexabromobenzene (HBB, 30%), and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTeBB, 23%). The relative trophic position of seals, estimated using stable isotopes, did not vary over time and did not influence flame retardant blubber concentrations. The relative carbon source increased over time at Arviat and Resolute Bay and weak relationships were observed with ΣPBDEs in blubber of seals. ΣPBDEs increased significantly from 1998 to 2008 in ringed seals from East Baffin and subsequently decreased in recent years. PBDE levels at other sites fluctuated slightly over time. HBCDD concentrations increased at several sites over the past decade. The presence of flame retardants in ringed seals suggests their persistence and their continuous inputs in the Canadian Arctic environment. Monitoring and research on the effects of these contaminants in seals are warranted given the importance of this species in Arctic marine food webs and for local communities.

Endothelin-1: Biosynthesis, Signaling and Vasoreactivity.

Endothelin-1 (ET-1) is an extremely potent vasoconstrictor peptide originally isolated from endothelial cells. Its synthesis, mainly regulated at the gene transcription level, involves processing of a precursor by a furin-type proprotein convertase to an inactive intermediate, big ET-1. The latter peptide can then be cleaved directly by an endothelin-converting enzyme (ECE) into ET-1 or reach the active metabolite through a two-step process involving chymase hydrolyzing big ET-1 to ET-1 (1-31), itself needing conversion to ET-1 by neprilysin (NEP) to exert physiological activity. ET-1 signals through two G protein-coupled receptors, endothelin receptor A (ETA) and endothelin receptor B (ETB). Both receptors induce an increase in intracellular Ca(2+), mainly from the extracellular space through voltage-independent mechanisms, the receptor-operated channels and store-operated channels. ET-1 also induces signaling through epidermal growth factor receptor transactivation, oxidative stress induction, rho-kinase, and the activation (ETA) or inhibition (ETB) of the adenylate cyclase/cyclic adenosine monophosphate pathway. Arterial vasoconstriction is mediated mainly by the ETA receptor. ET-1, via endothelium-located ETB, relaxes arteries or constricts vessels following activation of the same receptor type on the smooth muscle, where it can interact with ETA. In addition, ETB-dependent vasoconstriction seems more prominent in the venous vasculature. A better understanding of how ET-1 is synthesized and how ETA and ETB receptors interact could help design better pharmacological agents in the treatment of cardiovascular diseases where targeting the ET-1 system is indicated.

Body Perception and Action Following Deafness.

The effect of deafness on sensory abilities has been the topic of extensive investigation over the past decades. These investigations have mostly focused on visual capacities. We are only now starting to investigate how the deaf experience their own bodies and body-related abilities. Indeed, a growing corpus of research suggests that auditory input could play an important role in body-related processing. Deafness could therefore disturb such processes. It has also been suggested that many unexplained daily difficulties experienced by the deaf could be related to deficits in this underexplored field. In the present review, we propose an overview of the current state of knowledge on the effects of deafness on body-related processing.

Production of morphologically derived words in the semantic variant of primary progressive aphasia: preserved decomposition and composition but impaired validation.

Although there is growing interest in inflectional morphology in semantic variant primary progressive aphasia (svPPA), derivational morphology has rarely been studied in this population. This study reports the performance of N.G., a 72-year-old-woman with svPPA in a verb production task designed to entail morphological processing (composition, decomposition) and self-appraisal of her productions. N.G. demonstrated an over-reliance on morphological processing and failures in her appraisal of root/affix combinations that resulted in the production of morphological paraphasias and neologisms. Her performance in lexical decision of verbs and pseudo-verbs points to the involvement of semantic impairment in these difficulties.

Improving verb anomia in the semantic variant of primary progressive aphasia: the effectiveness of a semantic-phonological cueing treatment.

The semantic variant of primary progressive aphasia (svPPA) is known to affect the comprehension and production of all content words, including verbs. However, studies of the treatment of anomia in this disorder focused on relearning object names only. This study reports treatment of verb anomia in an individual with svPPA. The semantic-phonological cueing therapy resulted in significant improvement in naming abilities, for treated verbs only. This case study demonstrates that improvement in verb-naming abilities may be possible in svPPA. The almost complete maintenance of the treatment's effects in the patient 4 weeks after the end of the therapy also suggests improvements may be durable, at least in the short term, for some individuals with svPPA.

High salt-induced hypertension in B2 knockout mice is corrected by the ETA antagonist, A127722.

BACKGROUND AND PURPOSE: The contribution of endothelin-1 (ET-1) in a B2KO mouse model of a high salt-induced arterial hypertension was investigated. EXPERIMENTAL APPROACH: Wild-type (WT) or B2KO mice receiving a normal diet (ND) or a high-salt diet (HSD) were monitored by radiotelemetry up to a maximum of 18 weeks. At the 12th week of diet, subgroups under ND or HSD received by gavage the ETA antagonist A127722 during 5 days. In addition, blood samples were collected and, following euthanasia, the lungs, heart and kidneys were extracted, homogenized and assayed for ET-1 by RIA. In a separate series of experiments, the ETA antagonist, BQ123 was tested against the pressor responses to a NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) in anaesthetized WT and B2KO mice. KEY RESULTS: In B2KO, but not WT mice, 12 weeks of HSD triggered a maximal increase of the mean arterial pressure (MAP) of 19.1 ± 2.8 mmHg, which was corrected by A127722 to MAP levels found in B2KO mice under ND. Significant increases in immunoreactive ET-1 were detected only in the lungs of B2KO mice under HSD. On the other hand, metabolic studies showed that sodium urinary excretion was markedly reduced in B2KO compared with WT mice under ND. Finally, BQ123 (2 mg·kg(-1)) reduced by 50% the pressor response to L-NAME (2 mg·kg(-1)) in B2KO, but not WT mice under anaesthesia. CONCLUSIONS AND IMPLICATIONS: Our results support the concept that functional B2 receptors oppose high salt-induced increments in MAP, which are corrected by an ETA receptor antagonist in this mouse model of experimental hypertension.

PCB concentrations in lake trout (Salvelinus namaycush) are correlated to habitat use and lake characteristics.

This study considers the importance of lake trout habitat as a factor determining persistent organochlorine (OC) concentration. Lake trout is a stenothermal, cold water species and sensitive to hypoxia. Thus, factors such as lake depth, thermal stratification, and phosphorus enrichment may determine not only which lakes can support lake trout but may also influence among-lake variability in lake trout population characteristics including bioaccumulation of OCs. A survey of 23 lakes spanning much of the natural latitudinal distribution of lake trout provided a range of lake trout habitat to test the hypothesis that lake trout with greater access to littoral habitat for feeding will have lower concentrations of OCs than lake trout that are more restricted to pelagic habitat. Using the delta13C stable isotope signature in lake trout as an indicator of influence of benthic littoral feeding, we found a negative correlation between lipid-corrected delta13C and sigmaPCB concentrations supporting the hypothesis that increasing accessto littoral habitat results in lower OCs in lake trout. The prominence of mixotrophic phytoplankton in lakes with more contaminated lake trout indicated the pelagic microbial food web may exacerbate the biomagnification of OCs when lake trout are restricted to pelagic feeding. A model that predicted sigmaPCB in lake trout based on lake area and latitude (used as proximate variables for proportion of littoral versus pelagic habitat and accessibility to littoral habitat respectively) explained 73% of the variability in sigmaPCBs in lake trout in the 23 lakes surveyed.

Endothelin-1 (1-31): from chymase-dependent synthesis to cardiovascular pathologies.

The mast cell-derived serine protease chymase is importantly involved not only in degradation, but in synthesis of bioactive peptides as well. Several studies suggest that chymase is the predominant enzyme in the production of angiotensin II (Ang II) from angiotensin-I in interstitial tissues. Interestingly, chymase has also been suggested to mature endothelin-1 (ET-1) from its precursor, big-ET-1 in vitro. The lack of availability of specific chymase inhibitors, beyond the chymotrypsin-like inhibitor chymostatin, currently hampers the investigation of the chymase/ET-1/Ang II paradigm in physiology and cardiovascular diseases. Nonetheless, the recent advent of highly selective chymase inhibitors is shedding new light on the role of this enzymatic pathway in the several inflammatory prone vascular diseases as summarized in the present review. Considering increasing evidence towards significant interactions between Ang II and ET-1 in cardiovascular diseases, the present review will address the role of chymase in the production of those two peptides. Whether chymase-dependent production of ET-1 plays an important role in cardiovascular pathologies will also be discussed.

Leiomyosarcoma of urinary bladder following cyclophosphamide therapy: report of two cases.

Leiomyosarcoma of urinary bladder is rare, although it is the most common mesenchymal tumor in adults. We report two cases of this tumor following cyclophosphamide therapy. The first case is from a 53-year-old man with Wegener's granulomatosis treated for 6 years with cyclophosphamide. He presented with painless hematuria, and the initial biopsy of the bladder tumor revealed a malignant spindle cell neoplasm. A final diagnosis of leiomyosarcoma was made on radical cystoprostatectomy. The second example is from a 21-year-old man who had received cyclophosphamide in early infancy for a bilateral retinoblastoma. He also presented with painless hematuria, and a bladder tumor was resected transurethrally and diagnosed as leiomyosarcoma. He underwent partial cystectomy two months later. Cyclophosphamide, when used for a neoplastic or non-neoplastic condition, is associated with an increased risk of developing bladder cancer. The distribution of histologic subtypes differs from that seen in spontaneous bladder tumors. A review of the literature shows an increased proportion of squamous cell carcinomas and sarcomas, especially leiomyosarcomas in cyclophosphamide exposed patients. Acrolein, a cytotoxic metabolite of cyclophosphamide excreted in urine, is regarded as the most likely causative agent.

Intestinal epithelial cell differentiation involves activation of p38 mitogen-activated protein kinase that regulates the homeobox transcription factor CDX2.

The intracellular signaling pathways responsible for cell cycle arrest and differentiation along the crypt-villus axis of the human small intestine remain largely unknown. p38 mitogen-activated protein kinases (MAPKs) have recently emerged as key modulators of various vertebrate cell differentiation processes. In order to elucidate further the mechanism(s) responsible for the loss of proliferative potential once committed intestinal cells begin to differentiate, the role and regulation of p38 MAPK with regard to differentiation were analyzed in both intact epithelium as well as in well established intestinal cell models recapitulating the crypt-villus axis in vitro. Results show that phosphorylated and active forms of p38 were detected primarily in the nuclei of differentiated villus cells. Inhibition of p38 MAPK signaling by 2-20 microm SB203580 did not affect E2F-dependent transcriptional activity in subconfluent Caco-2/15 or HIEC cells. p38 MAPK activity dramatically increased as soon as Caco-2/15 cells reached confluence, whereas addition of SB203580 during differentiation of Caco-2/15 cells strongly attenuated sucrase-isomaltase gene and protein expression as well as protein expression of villin and alkaline phosphatase. The binding of CDX2 to the sucrase-isomaltase promoter and its transcriptional activity were significantly reduced by SB203580. Pull-down glutathione S-transferase and immunoprecipitation experiments demonstrated a direct interaction of CDX3 with p38. Finally, p38-dependent phosphorylation of CDX3 was observed in differentiating Caco-2/15 cells. Taken together, our results indicate that p38 MAPK may be involved in the regulation of CDX2/3 function and intestinal cell differentiation.

Characterization of oxalate oxidase and cell death in Al-sensitive and tolerant wheat roots.

Several genes including oxalate oxidase (Oxo) are up-regulated in Triticum aestivum L. root tips exposed to Al. To better understand the function of Oxo during Al exposure, the protein level and enzyme activity were measured. The data indicate that both Oxo protein and activity are increased proportionally to the level of root growth inhibition (RGI). A high level of Oxo expression may result in excess H(2)O(2) production which could become toxic and induce cell death. However, the timing of H(2)O(2) production (observed after 24 h) indicates that it cannot be the primary cause of cell death first observed after 8 h. Moreover, at Al concentrations resulting in 50% RGI, we did not observe any cell death in the sensitive cultivar while a punctated pattern of death involving small groups of cells was found in the tolerant cultivar. This pattern was maintained for several days in the tolerant cultivar, suggesting the involvement of a cell death mechanism aimed at replacing epidermal cells intoxicated with Al while root growth is maintained. The accelerated epidermal cell turnover may represent a new detoxification mechanism helping to protect deeper cell layers of the meristematic and elongation zone essential for root growth.