Trehalose, an mTOR Independent Autophagy Inducer, Alleviates Human Podocyte Injury after Puromycin Aminonucleoside Treatment

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Caractérisation hydrogéochimique des eaux des aquifères fissurés de la zone Guiglo-Duekoué (Ouest de la Côte d’Ivoire)

La zone d’étude, Guiglo-Duekoué, est située à l’Ouest de la Côte d’Ivoire, entre les latitudes 7°00’ et 7°42’ Nord et les longitudes 6°28’ et 6°50’ Ouest. Cette étude vise à faire une analyse hydrogéochimique les eaux souterraines de la région de Guiglo-Duekoué. L’approche méthodologique est basée sur la détermination des hydrofaciès à partir des diagrammes de Piper et de Schoeller-Berkaloff et l’étude de la qualité des eaux qui s’est appuyée sur une analyse comparative des teneurs des paramètres physico-chimiques aux normes OMS. Les résultats de l’étude ont montré que les eaux sont bicarbonatées calciques et magnésiennes (95,83%) et bicarbonatées sodi-potassiques (4,17%). Ces eaux ont des températures qui varient entre 25,7 °C et 28,9 °C, avec une moyenne de 26,7 °C. Leurs pH oscillent entre 6,51 et 7,13, avec une moyenne de 6,67. La turbidité des eaux souterraines reste très faible avec des valeurs qui varient entre 0,20 NTU et 1,01 NTU, pour une moyenne de 0,49 NTU. La conductivité électrique des eaux varie entre 106 μS/cm et 349 μS/cm, avec une moyenne de 208,437 μS/cm. La majorité des échantillons d’eau a une conductivité électrique comprise entre 100 μs/cm et 250 μs/cm (68,75%). La dureté des eaux est comprise entre 2,8 °F et 15,40 °F, avec une moyenne de 6,41 °F. La qualité physico-chimique des eaux souterraines étudiées est conforme dans l’ensemble aux normes recommandées par l’OMS et ne présentent pas de danger majeur pour la consommation humaine. Cependant, il existe de fortes teneurs en fer (0,66 mg/L) et en manganèse (0,16 mg/L), ce qui explique l’apparence rougeâtre et le goût désagréable de ces eaux.Mots clés: Eaux souterraines; Diagrammes d’analyses hydrochimiques; Normes de l’OMS; faciès hydrochimiques; Potabilité; Région ouest semi-montagneus

Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis

BACKGROUND: Our previous study demonstrated that the disruption of cholesterol homeostasis promotes tubulointerstitial injury in diabetic nephropathy (DN). This study aimed to further investigate the effects of gut microbiota dysbiosis on this process and explored its potential mechanism. METHODS: Diabetic rats treated with broad-spectrum oral antibiotics or faecal microbiota transplantation (FMT) from the healthy donor group and human kidney 2 (HK-2) cells stimulated with sodium acetate were used to observe the effects of gut microbiota on cholesterol homeostasis. The gut microbiota distribution was measured by 16S rDNA sequencing with faeces. Serum acetate level was examined by gas chromatographic analysis. Protein expression of G protein coupled receptor 43 (GPR43) and molecules involved in cholesterol homeostasis were assessed by immunohistochemical staining, immunofluorescence staining, and Western Blotting. RESULTS: Depletion of gut microbiota significantly attenuated albuminuria and tubulointerstitial injury. Interestingly, serum acetate levels were also markedly decreased in antibiotics-treated diabetic rats and positively correlated with the cholesterol contents in kidneys. An in vitro study demonstrated that acetate significantly increased cholesterol accumulation in HK-2 cells, which was caused by increased expression of proteins mainly modulating cholesterol synthesis and uptake. As expected, FMT effectively decreased serum acetate levels and alleviated tubulointerstitial injury in diabetic rats through overriding the disruption of cholesterol homeostasis. Furthermore, GPR43 siRNA treatment blocked acetate-mediated cholesterol homeostasis dysregulation in HK-2 cells through decreasing the expression of proteins governed cholesterol synthesis and uptake. CONCLUSIONS: Our studies for the first time demonstrated that the acetate produced from gut microbiota mediated the dysregulation of cholesterol homeostasis through the activation of GPR43, thereby contributing to the tubulointerstitial injury of DN, suggesting that gut microbiota reprogramming might be a new strategy for DN prevention and therapy

GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity

RATIONALE: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear. METHODS: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces. RESULTS: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate. CONCLUSION: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity

Gene expression drives the evolution of dominance.

Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance in natural populations is poorly quantified. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arises as a consequence of the functional importance of genes and their optimal expression levels

Geometric Mixing, Peristalsis, and the Geometric Phase of the Stomach

Mixing fluid in a container at low Reynolds number - in an inertialess environment - is not a trivial task. Reciprocating motions merely lead to cycles of mixing and unmixing, so continuous rotation, as used in many technological applications, would appear to be necessary. However, there is another solution: movement of the walls in a cyclical fashion to introduce a geometric phase. We show using journal-bearing flow as a model that such geometric mixing is a general tool for using deformable boundaries that return to the same position to mix fluid at low Reynolds number. We then simulate a biological example: we show that mixing in the stomach functions because of the "belly phase": peristaltic movement of the walls in a cyclical fashion introduces a geometric phase that avoids unmixing.Comment: Revised, published versio

Algorithms for the minimum non-separating path and the balanced connected bipartition problems on grid graphs (With erratum)

For given a pair of nodes in a graph, the minimum non-separating path problem looks for a minimum weight path between the two nodes such that the remaining graph after removing the path is still connected. The balanced connected bipartition (BCP$_2$) problem looks for a way to bipartition a graph into two connected subgraphs with their weights as equal as possible. In this paper we present an algorithm in time $O(N\log N)$ for finding a minimum weight non-separating path between two given nodes in a grid graph of $N$ nodes with positive weight. This result leads to a 5/4-approximation algorithm for the BCP$_2$ problem on grid graphs, which is the currently best ratio achieved in polynomial time. We also developed an exact algorithm for the BCP$_2$ problem on grid graphs. Based on the exact algorithm and a rounding technique, we show an approximation scheme, which is a fully polynomial time approximation scheme for fixed number of rows.Comment: With erratu

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Idiopathic adult intussusception

Intussusception is an uncommon cause of abdominal pain in adults and poses diagnostic challenges for emergency physicians, due to its varied presenting symptoms and time course. Diagnosis is thus often delayed and results in surgical intervention due to the development of bowel ischaemia. We report on a young patient who presented with an ileo-ileal intussusception in whom there were no underlying lesions identified as a causal factor