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Objective: Leptin, a hormone that regulates food intake and energy metabolism, is present in breast milk. The aim of this study was to determine whether milk leptin concentration is correlated with maternal circulating leptin and BMI and with body weight gain of infants. Research Methods and Procedures: A group of 28 non‐obese women (BMI between 16.3 and 27.3 kg/m2) who breast‐fed their infants for at least 6 months and their infants were studied. Venous blood and milk samples were obtained from mothers at 1, 3, 6, and 9 months of lactation, and leptin concentration was determined. Infant body weight and height were followed until 2 years of age. Results: During the whole lactation period, milk leptin concentration correlated positively with maternal plasma leptin concentration and with maternal BMI. In addition, milk leptin concentration at 1 month of lactation was negatively correlated with infant BMI at 18 and 24 months of age. A better negative correlation was also found between log milk leptin concentration at 1 and at 3 months of lactation and infant BMI from 12 to 24 months of age. Discussion: We concluded that, in a group of non‐obese mothers, infant body weight during the first 2 years may be influenced by milk leptin concentration during the first stages of lactation. Thus, moderate milk‐borne maternal leptin appears to provide moderate protection to infants from an excess of weight gain. These results seem to point out that milk leptin is an important factor that could explain, at least partially, the major risk of obesity of formula‐fed infants with respect to breast‐fed infants. 相似文献
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Christina Ginkel Dieter Hartmann Katharina vom Dorp Armin Zlomuzica Hany Farwanah Matthias Eckhardt Roger Sandhoff Joachim Degen Mariona Rabionet Ekrem Dere Peter D?rmann Konrad Sandhoff Klaus Willecke 《The Journal of biological chemistry》2012,287(50):41888-41902
Ceramide synthase 1 (CerS1) catalyzes the synthesis of C18 ceramide and is mainly expressed in the brain. Custom-made antibodies to a peptide from the C-terminal region of the mouse CerS1 protein yielded specific immunosignals in neurons but no other cell types of wild type brain, but the CerS1 protein was not detected in CerS1-deficient mouse brains. To elucidate the biological function of CerS1-derived sphingolipids in the brain, we generated CerS1-deficient mice by introducing a targeted mutation into the coding region of the cers1 gene. General deficiency of CerS1 in mice caused a foliation defect, progressive shrinkage, and neuronal apoptosis in the cerebellum. Mass spectrometric analyses revealed up to 60% decreased levels of gangliosides in cerebellum and forebrain. Expression of myelin-associated glycoprotein was also decreased by about 60% in cerebellum and forebrain, suggesting that interaction and stabilization of oligodendrocytic myelin-associated glycoprotein by neuronal gangliosides is due to the C18 acyl membrane anchor of CerS1-derived precursor ceramides. A behavioral analysis of CerS1-deficient mice yielded functional deficits including impaired exploration of novel objects, locomotion, and motor coordination. Our results reveal an essential function of CerS1-derived ceramide in the regulation of cerebellar development and neurodevelopmentally regulated behavior. 相似文献
146.
Lluís Palou Clara Montesinos‐Herrero Cristina Besada Verònica Taberner 《Journal of Phytopathology》2013,161(9):625-631
Three different fungi (isolates IVIA QCV‐1, IVIA QCV‐3 and IVIA QCV‐4) were isolated as potential causal agents of postharvest decay losses observed on sweet persimmons (Diospyros kaki L.) cv. ‘Rojo Brillante’ from commercial packinghouses in the Valencia area (Spain). Disease symptoms were irregular brownish and soft lesions mainly located under and surrounding the fruit calyx (stem‐end) that expanded rapidly at room temperature and turned to dark brown or black colour producing apparent and in some cases abundant white to grey mycelium. The identification of Lasiodiplodia theobromae, Neofusicoccum mediterraneum and Neofusicoccum luteum by macroscopic and microscopic morphological observations was confirmed with the amplification and subsequent sequencing of the ribosomal DNA ITS2 region. Representative nucleotide sequences were deposited in GenBank. Pathogenicity of all three isolates was demonstrated by fulfilling Koch's postulates. 相似文献
147.
Alba Naudí Mariona Jové Victoria Ayala Rosanna Cabré Manuel Portero-Otin Isidre Ferrer Reinald Pamplona 《Revista espa?ola de geriatría y gerontología》2013
Introduction
The concept of ‘selective neuronal vulnerability’ refers to the differential sensitivity of neuronal populations in the nervous system to stresses that cause cell damage and lead to neurodegeneration. Because oxidative stress play a causal role in the physiological aging process, and it is often invoked as an aetiopathogenic and/or pathophysiological mechanism for neurodegeneration, in the present work we propose that the molecular bases of selective neuronal vulnerability is linked with cell adaptations related to oxidative stress.Material and methods
The grey substance of 5 different regions from healthy human subjects (n = 7) were selected: i) to evaluate their membrane fatty acid profile by chromatographic methods, ii) to determine their membrane susceptibility to peroxidation, and iii) to recognise potential mechanisms involved in its regulation.Results
The results showed significant inter-regional differences in the fatty acid profile, basically due to the content of mono- and highly polyunsaturated fatty acids; changes that, in turn, induce significant differences in theirs susceptibilities to peroxidation, as well as differences that can be ascribed to the desaturase activity.Conclusion
Thus, the cross-regional comparative approach seems to confirm the idea that the level of cell membrane unsaturation may be a key trait associated with selective neuronal vulnerability. 相似文献148.
Martins IM Cortés JC Muñoz J Moreno MB Ramos M Clemente-Ramos JA Durán A Ribas JC 《The Journal of biological chemistry》2011,286(5):3484-3496
Three specific β(1,3)glucan synthase (GS) inhibitor families, papulacandins, acidic terpenoids, and echinocandins, have been analyzed in Schizosaccharomyces pombe wild-type and papulacandin-resistant cells and GS activities. Papulacandin and enfumafungin produced similar in vivo effects, different from that of echinocandins. Also, papulacandin was the strongest in vitro GS inhibitor (IC(50) 10(3)-10(4)-fold lower than with enfumafungin or pneumocandin), but caspofungin was by far the most efficient antifungal because of the following. 1) It was the only drug that affected resistant cells (minimal inhibitory concentration close to that of the wild type). 2) It was a strong inhibitor of wild-type GS (IC(50) close to that of papulacandin). 3) It was the best inhibitor of mutant GS. Moreover, caspofungin showed a special effect for two GS inhibition activities, of high and low affinity, separated by 2 log orders, with no increase in inhibition. pbr1-8 and pbr1-6 resistances are due to single substitutions in the essential Bgs4 GS, located close to the resistance hot spot 1 region described in Saccharomyces and Candida Fks mutants. Bgs4(pbr)(1-8) contains the E700V change, four residues N-terminal from hot spot 1 defining a larger resistance hot spot 1-1 of 13 amino acids. Bgs4(pbr)(1-6) contains the W760S substitution, defining a new resistance hot spot 1-2. We observed spontaneous revertants of the spherical pbr1-6 phenotype and found that an additional A914V change is involved in the recovery of the wild-type cell shape, but it maintains the resistance phenotype. A better understanding of the mechanism of action of the antifungals available should help to improve their activity and to identify new antifungal targets. 相似文献
149.
Duch A Palou G Jonsson ZO Palou R Calvo E Wohlschlegel J Quintana DG 《The Journal of biological chemistry》2011,286(4):2486-2491
An intra-S phase checkpoint slows the rate of DNA replication in response to DNA damage and replication fork blocks in eukaryotic cells. In the budding yeast Saccharomyces cerevisiae, such down-regulation is achieved through the Rad53 kinase-dependent block of origins of replication. We have identified the Rad53 phosphorylation sites on Dbf4, the activator subunit of the essential S phase Dbf4-dependent kinase, and generated a non-phosphorylatable Dbf4 mutant (dbf4(7A)). We show here that dbf4(7A) is a bona fide intra-S phase checkpoint bypass allele that contributes to abrogating the Rad53 block of origin firing in response to genotoxic stress. 相似文献
150.
Aparicio E Franco S Parera M Andrés C Tural C Clotet B Martínez MA 《Journal of virology》2011,85(12):5961-5969
The role of the hepatitis C virus (HCV) NS3/4A protease in ablating the signaling pathway involved in the production of alpha/beta interferon (IFN-α/β) suggests a relationship between NS3/4A proteolytic activity and a patient's response to IFN-based therapy. To identify viral factors associated with the HCV treatment response, we analyzed the pretreatment NS3/4A protease gene quasispecies composition of 56 HCV genotype 1-HIV-1-coinfected patients treated in our clinic with pegylated IFN (pegIFN) plus ribavirin (RBV). The catalytic efficiency of the dominant (i.e., the most abundant) quasispecies was also assayed for Cardif cleavage and correlated with treatment outcome. A total of 1,745 clones were isolated and sequenced. Significantly less nucleotide quasispecies heterogeneity and lower Shannon entropy values were detected within the responder group (P < 0.05). A correlation was also found between the efficiency of NS3/4A protease Cardif cleavage and therapy outcome. Proteases from sustained responder patients were more efficient at processing Cardif (mean ± standard error of the mean [SEM], 0.8960 ± 0.05568; n = 19) than proteases from nonresponders (mean ± SEM, 0.7269 ± 0.05306; n = 37; P < 0.05). Finally, the amino acid p distance (the proportion [p] of nucleotide sites at which two sequences being compared are different) was significantly shorter in patients with an interleukin-28B (IL-28B) risk allele (P < 0.01), suggesting that IL-28B risk allele carriers exert a lower positive selection pressure on the NS3/4A protease. NS3/4A protease efficiency in cleaving Cardif may be associated with the pegIFN-RBV treatment response, as shown in our cohort of HIV-HCV-coinfected patients. Greater NS3/4A nucleotide heterogeneity and higher Shannon entropy values in nonresponders suggest that less HCV quasispecies complexity may favor a better response to pegIFN-RBV. 相似文献