Étude de la formation et de la stabilité des mousses chimiques de surface de la Vienne

Le recensement de la charge polluante rejetée dans la rivière Vienne (France) par les usines et les stations d'épuration de Limoges à Confolens a été effectué. Des campagnes de prélèvement et d'observations visuelles ont permis de localiser les lieux d'apparition de mousses en aval d'usines de fabrication de pâte à papier et de cartons. L'étude du pouvoir moussant des mélanges des deux principaux rejets polluants (papeterie et cartonnerie) a permis de mettre en évidence des phénomènes de synergie entre certains mélanges se traduisant à la fois par une augmentation du pouvoir moussant et de la stabilité de la mousse dans le temps. L'étude par « HPLC » montre l'apparition de pics supplémentaires confirmant l'interaction entre les constituants des rejets; le principal effluent a pu être suivi à l'aide de ses caractéristiques chimiques dans la rivière et dans les mousses jusqu'à Confolens.The study reported here considers of the formation and stability of foam on the Vienne river. Foaming is frequently encountered in relation to the discharge of industrial effluents, especially from the paper industry (CRAIG and al., 1990). Earlier papers have investigated the consequences of such discharges (NEILSON and al., 1990; KALLQVIST and al., 1989; SRIVASTAVA and al. 1988).The extent of foam formation is determined by a number of factors, including effluent composition, turbulence of the stream, etc. Foams stability requires the presence of long chain fatty acids, amine acids, tannins etc. Many industries discharge their effluents into the Vienne river (paper and cardboard industries, leather dressing plants and tanneries).An inventory of the main urban and industrial discharges has been established (Map 1). The effluents from the pulp, paper and cardboard industries provide the main pollution foad in terms of volume, COD, suspended solids (SS) and anionic surfactants.A visual survey allowed us to locus our investigations on the places where persistant foams appear, especially downstream of Saillat below the discharges from Aussedat Rey and SGPL (Picture 1), and below small waterfalls (Pont de Pilas, Chabanais, Ansac...). At Confolens, the foams are most stable and form stable drifting foam residues.Synergistic foaming effects have been reported due to the combination of polyamides and tannins (BIKERMAN, 1953). We have chosen to analyze the main effluents (Table 1) and their mixtures in relation to foaming (foaming capacity, foaming stability and surfactant analysis). The method used for foaming capacity determination was based on the hand shaking of 250 ml bottles. The stability of the foam was defined as the time for which the height of foam persists. Anionic surfactants were present at significant concentrations, varying from 1 mg/l (as sodium dodecyl sulphate) in the Aussedat Rey effluent to 4 mg/l in the SGPL effluent and 7 mg/l in the St Junien wastewater treatment plant effluent. The maximum foaming capacity was obtained for a 70/30 Aussedat Rey/SGPL effluent mixture (Fig. 1). The foaming capacity persists river time, remaining practically unchanged for three days. After 6 days, the maximum foaming capacity appears to be reduced. Foam stability is also maximum for the same 70/30 mixture (Fig. 2). After 6 days, the 50/50 and 70/30 mixtures can still produce 3 cm of foam that persist for 2 hours (Fig. 3).For HPLC analysis (20 µl samples), the effluents from AR and the effluents from SGPL (or the mixture of the two) were diluted in 10 times their volume of distilled water prior to analysis. Concerning the mixture 95 % AR - 5 % SGPL (95/5) the peak that characterizes the SGPL effluent starts appearing and growing at 6.76 min. With the proportions : 90/10 and 70/30, its retention time respectively diminishes from 6.34 min. to 5.58 min. Moreover an extra peak appears with the 70/30 mixture at 5.02 min. This extra peak is at its highest at 4.96 min. for a 50/50 mixture. At the same time the initial AR peak is decreasing. It is thus confirmed that one or more constituent: are formed on mixing the two effluents, as indicated by the synergistic effect described earlier for the foam capacity and stability analysis.Anionic surfactants were analyzed in the Vienne river (Fig. 5). Their concentration dramatically increase at point (4) (Pont de Pilas), just below the discharges from AR and SGPL. When the river flow increases, dilution masks the phenomenon. A drastic decrease in pollution appears in August when the industrial activity is reduced because of holidays (Fig. 7).The HPLC Vienne river analysis (Fig. 5) shows an important peak of pollution at point (4) (Pont de Pilas) characteristic of the AR effluent. At Chabanais point (5), the ARISGPL ratio is 95/5 and the peak of SGPL appears, perhaps, et 6.12 min (in the diluted effluents in the same ratio 95/5, it appears at 6.34 min). At Confolens (10), the intensity has diminished (after two days) and the Confolens foams are the same as those produced by a river sample without concentrated effect. No appreciable degradation has occurred, since the height of the peaks point 10 is similar as those of the chromatogram of point (5) in accord with the literature (LESZKIEWICZ and KINNER, 1988 ; COTE and OTIS, 1989)

Deciphering neuronal deficit and protein profile changes in human brain organoids from patients with creatine transporter deficiency

Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human brain organoids from induced pluripotent stem cells of healthy subjects and CTD patients. Brain organoids from CTD donors had reduced creatine uptake compared with those from healthy donors. The expression of neural progenitor cell markers SOX2 and PAX6 was reduced in CTD-derived organoids, while GSK3β, a key regulator of neurogenesis, was up-regulated. Shotgun proteomics combined with integrative bioinformatic and statistical analysis identified changes in the abundance of proteins associated with intellectual disability, epilepsy, and autism. Re-establishment of the expression of a functional SLC6A8 in CTD-derived organoids restored creatine uptake and normalized the expression of SOX2, GSK3β, and other key proteins associated with clinical features of CTD patients. Our brain organoid model opens new avenues for further characterizing the CTD pathophysiology and supports the concept that reinstating creatine levels in patients with CTD could result in therapeutic efficacy

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease. Cabrera-Serrano et al. show that biallelic loss-of-function variants in the gene encoding obscurin (OBSCN) predispose individuals to recurrent and severe episodes of rhabdomyolysis, typically with onset in the teenage years.Peer reviewe

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca²⁺ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca²⁺ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca²⁺ back into the sarcoplasmic reticulum and/or a decrease in Ca²⁺ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.Macarena Cabrera-Serrano, Laure Caccavelli, Marco Savarese, Anna Vihola, Manu Jokela, Mridul Johari, Thierry Capiod, Marine Madrange, Enrico Bugiardini, Stefen Brady, Rosaline Quinlivan, Ashirwad Merve, Renata Scalco, David Hilton-Jones, Henry Houlden, Halil Ibrahim Aydin, Serdar Ceylaner, Sarah Drewes, Jerry Vockley, Rhonda L. Taylor, Chiara Folland, Aasta Kelly, Hayley Goullee, Emil Ylikallio, Mari Auranen, Henna Tyynismaa, Bjarne Udd, Alistair R. R. Forrest, Mark R. Davis, Drago Bratkovic, Nicholas Manton, Thomas Robertson, Cullen O, Gorman, Pamela McCombe, Nigel G. Laing, Liza Phillips, Pascale de Lonlay, and Gianina Ravenscrof

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified ten bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in SR function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in SR Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the SR and/or a decrease in Ca2+ SR storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified ten bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in SR function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in SR Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the SR and/or a decrease in Ca2+ SR storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.</p