SEC23B Loss-of-Function Suppresses Hepcidin Expression by Impairing Glycosylation Pathway in Human Hepatic Cells

Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells.     

Synapses: The Brain’s Energy-Demanding Sites

The brain is one of the most energy-consuming organs in the mammalian body, and synaptic transmission is one of the major contributors. To meet these energetic requirements, the brain primarily uses glucose, which can be metabolized through glycolysis and/or mitochondrial oxidative phosphorylation. The relevance of these two energy production pathways in fulfilling energy at presynaptic terminals has been the subject of recent studies. In this review, we dissect the balance of glycolysis and oxidative phosphorylation to meet synaptic energy demands in both resting and stimulation conditions. Besides ATP output needs, mitochondria at synapse are also important for calcium buffering and regulation of reactive oxygen species. These two mitochondrial-associated pathways, once hampered, impact negatively on neuronal homeostasis and synaptic activity. Therefore, as mitochondria assume a critical role in synaptic homeostasis, it is becoming evident that the synaptic mitochondria population possesses a distinct functional fingerprint compared to other brain mitochondria. Ultimately, dysregulation of synaptic bioenergetics through glycolytic and mitochondrial dysfunctions is increasingly implicated in neurodegenerative disorders, as one of the first hallmarks in several of these diseases are synaptic energy deficits, followed by synapse degeneration.     

Anti-inflammatory effect of aqueous extracts of roasted and green Coffea arabica L.

Green coffee contains a large quantity and variety of polyphenols and flavonoids. The roasting affects the composition of the polyphenols in coffee, due to the formation of compounds generated by Maillard reaction, which can have anti-inflammatory or antioxidant potential. The anti-inflammatory and antioxidant effects of aqueous extracts of green (AGCa) and roasted (ARCa) coffee beans were investigated in animal models and using a DPPH radical scavenging test. In the formalin test the extracts reduced licking activity only in the late phase. The inhibitory values of oedema at 3 h post-carrageenan were 53% and 74% for 100 and 300 mg/kg of the AGCa extract and 36% for ARCa (300 mg/kg). Leukocyte recruitment into the peritoneal cavity was inhibited by the extracts. The antioxidant activities of the extracts were higher than the reference antioxidants, ascorbic acid and butylated hydroxytoluene. These results indicate that coffee extracts exhibit anti-inflammatory and antioxidant properties.     

Safety assessment of Lactobacillus strains: presence of putative risk factors in faecal, blood and probiotic isolates

The widespread use of immunosuppressive therapy and antimicrobial agents as well as novel probiotics without a long history of safe use has increased requirements for safety assessment of probiotic lactobacilli. In this study 44 faecal, 52 blood and 15 probiotic isolates (including 3 dairy strains) of Lactobacillus were assayed for their adhesion properties to extracellular matrix proteins and mucus, hemolysis, ability to avoid the induction of respiratory burst in peripheral blood mononucleocytes (PMN) and resistance to human serum. Among tested strains adhesion to collagen, fibrinogen and mucus was isolate-specific and no statistically significant differences were obtained between faecal, blood and probiotic isolates. However, blood isolates showed a trend for higher adhesion to mucus than probiotic strains (P=0.07). Probiotic strains induced lower respiratory burst in PMN when compared to the blood isolates (P<0.05). Moreover, there was a positive correlation between adhesion to collagen and induction of respiratory burst for faecal isolates (P<0.05). In the determination of serum resistance, probiotic strains showed a trend for lower sensitivity to human serum-mediated killing when compared to the faecal isolates (P=0.07). None of the measurable virulence factors were found to be present at statistically higher level in clinical blood isolates when compared to faecal and/or probiotic isolates indicating that these factors do not cause risk when safety of probiotics is considered. However, the significance of adhesion to mucus, low induction of respiratory burst in PMN and resistance to human serum-mediated killing may need further evaluation in experimental animal models and in epidemiological data.     

Physical examination of arteriovenous fistula: The influence of professional experience in the detection of complications

Vascular access is one of the leading causes of mobilization of financial resources in health systems for people with chronic kidney disease on hemodialysis. Physical examination of the arteriovenous fistula (AVF) has demonstrated its effectiveness in identifying complications. We decided to evaluate the influence of nurses' professional experience in the detection of complications of the AVF (venous stenosis and steal syndrome). The study took place in eight hemodialysis centers between May and September of 2011 in the north of Portugal. Sample was constituted by registered nurses. The nurses involved in the experiment were divided in two groups: those who had more than 5 years of experience and those who had less than 5 years of experience. Ninety‐two nurses participated in the study: 34 nurses had less than 5 years of professional experience and 58 had more than 5 years of professional experience. In the practices considered by nurses in the detection of venous stenosis, there were no differences observed between the groups (P > 0.05). In steal syndrome, there were no differences observed between the groups in the practices of the nurses in the detection of this complication of the AVF (P > 0.05). We concluded that professional experience does not influence the detection of venous stenosis and steal syndrome.     

Fast Separation of Capsaicinoids from Peppers by Reversed Phase Ultra-Performance Liquid Chromatography: Comparation with Traditional High-Performance Liquid Chromatography Methods

A new chromatographic method for the separation of major capsaicinoids in peppers has been developed. Nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin, and homodihydrocapsaicin have been separated by reversed-phase ultra-performance liquid chromatography. A gradient method has been developed using two solvents: 0.1% acetic acid in water and 0.1% acetic acid in methanol. The developed method allows the full separation of capsaicinoids in less than 3 min, with high reproducibility (relative standard deviation < 4.3%) and repeatability (relative standard deviation < 3.6%). Robustness regarding the total amount of methanol in the sample was determined. Comparison with previous reversed-phase high-performance liquid chromatography methods using both monolithic and conventional columns was also studied. Finally, the method was applied in the determination of major capsaicinoids in 16 hot pepper samples produced in Spain.     

Is a sense of inequity an ancestral primate trait? Testing social inequity in cotton top tamarins (Saguinus oedipus).

To address a controversy in the literature concerning whether monkeys show an aversion to inequity, individuals of a New World monkey species, cotton top tamarins (Saguinus oedipus) were tested in an offering task and in a bartering task. At issue was whether the monkeys rejected rewards because of a violation of expectancy of the preferred reward, or whether they rejected rewards because of a sensitivity to socially mediated inequity. The data from both tasks indicated that the subjects were more likely to reject when preferred rewards were presented, either because of another animal eating the reward (the social condition) or because of rewards being presented but inaccessible. The bartering task led to the only behavioral indication of aversion due specifically to social inequity, which was demonstrated when tamarins' sensitivity to the difference in rewards increased with exposure to other tamarins working to receive the preferred rewards. The results suggest that social inequity aversion will be assessed by tamarins, and possibly by other primates, only under conditions of limited resources and a requirement of work, which may make the situation a bit more competitive and thus drives attention toward both social and reward evaluation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relating indices of knowledge structure coherence and accuracy to skill-based performance: Is there utility in using a combination of indices?

The authors examined the relative criterion-related validity of knowledge structure coherence and two accuracy-based indices (closeness and correlation) as well as the utility of using a combination of knowledge structure indices in the prediction of skill acquisition and transfer. Findings from an aggregation of 5 independent samples (N = 958) whose participants underwent training on a complex computer simulation indicated that coherence and the accuracy-based indices yielded comparable zero-order predictive validities. Support for the incremental validity of using a combination of indices was mixed; the most, albeit small, gain came in pairing coherence and closeness when predicting transfer. After controlling for baseline skill, general mental ability, and declarative knowledge, only coherence explained a statistically significant amount of unique variance in transfer. Overall, the results suggested that the different indices largely overlap in their representation of knowledge organization, but that coherence better reflects adaptable aspects of knowledge organization important to skill transfer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)