An ER-Localized SNARE Protein Is Exported in Specific COPII Vesicles for Autophagosome Biogenesis

The de novo formation of autophagosomes for the targeting of cytosolic material to the vacuole/lysosome is upregulated upon starvation. How autophagosomes acquire membranes remains still unclear. Here, we report that, in yeast, the endoplasmic reticulum (ER)-localized Qa/t-SNARE Ufe1 has a role in autophagy. During starvation, Ufe1 is increasingly exported from the ER and targeted to intracellular sites that contain the autophagy markers Atg8 and Atg9. In addition, Ufe1 interacts with non-ER SNARE proteins implicated in autophagosome formation. Loss of Ufe1 function impairs autophagy and results in fewer and smaller autophagosomes. Unlike conventional cargo, the ER export of Ufe1 is significantly reduced in sec23-1 cells, which affects the coat protein (COP)II complex, already at the permissive temperature. Under the same conditions, sec23-1 cells are hypersensitive to starvation and deficient in autophagy. Our data suggest that ER membranes containing Ufe1 are delivered to sites of autophagosome formation in specific COPII vesicles.EMBO short-term fellowship (EMBO ASTF) 293-2015Spanish, Ministry of ScienceSpanish Government BFU2009-07290Ramon y Cajal program Spanish Government BFU2014-59309-

Favourable pregnancy outcome in a woman with secondary pulmonary hypertension complicating mitral stenosis

Pulmonary hypertension (PH) is a rare condition with a high incidence of maternal and perinatal mortality (30–56% and 10–13%, respectively). Pulmonary hypertension is a contraindication to pregnancy because of high risk of maternal death, therefore the World Health Organisation (WHO) advises to discuss a termination in the event of pregnancy with women suffering from PH

Happy life in the late adulthood : the meaning of individual motive

Positive psychology points out the relation between experiencing the state of engagement in life, including social engagement, and the feeling of happiness and contentment in seniors. The purpose of the conducted study was to search for the relationship between the well-being of older adults and their individual life motives which were operationalized on the basis of the Japanese cultural phenomenon of ikigai. The participants in the study were seniors from three groups: members of the Active Senior Club, students of The Third Age University and inmates of a Care and Therapy In-patient Department (N = 138). The sense of meaning of life, satisfaction with life and resiliency were measured. Additionally, the participants were asked a question concerning the value they ascribed to their own life. The results of the study indicate that the seniors who declare they possess an individual life motive are generally more satisfi ed with their life and consider it to have more meaning. Senior citizens who are active in areas such as education or culture also present a higher level in those areas

Low Content of Cyclosporine A and Its Metabolites in the Colostrum of Post-Transplant Mothers

The rate of post-transplant mothers who breastfeed while on immunosuppression is progressively increasing. Data on breastfeeding while on cyclosporine-based regimens are limited. Therefore, we assessed the amount of cyclosporine and its metabolites that might be ingested by a breastfed infant by measuring the concentration of cyclosporine and its metabolites in the colostrum of seven post-transplant mothers. The mean concentration of cyclosporine in the colostrum was 22.40 ± 9.43 mcg/L, and the estimated mean daily dose of the drug was 1049.22 ± 397.41 ng/kg/24 h. Only three metabolites (AM1, DHCsA, and THCsA) had mean colostrum amounts comparable to or higher than cyclosporine itself, with the daily doses being 468.51 ± 80.37, 2757.79 ± 1926.11, and 1044.76 ± 948.56 ng/kg/24 h, respectively. Our results indicate a low transfer of cyclosporine and its metabolites into the colostrum in the first two days postpartum and confirm the emerging change to the policy on breastfeeding among post-transplant mothers. A full assessment of the safety of immunosuppressant exposure via breastmilk will require further studies with long-term follow-ups of breastfed children

Low Transfer of Tacrolimus and Its Metabolites into Colostrum of Graft Recipient Mothers

Currently, the majority of neonates born to organ recipient mothers on chronic immunosuppressive therapy are formula fed. However, over the past few years, evidence has grown, suggesting that breastfeeding might be possible and beneficial. We designed a study assessing the transfer of tacrolimus into the colostrum of posttransplant mothers. We assessed the amount of tacrolimus and its metabolites, M-1 and M-3, that would be ingested by the breastfed neonates. Concentrations of tacrolimus and its metabolites were measured in colostrum from 14 posttransplant mothers as well as in venous cord blood and venous blood of the neonates. Test material analysis was performed by liquid chromatography coupled with mass spectrometry (LC/MS). The amount of ingested formula was registered, which allowed for estimation of the amount of tacrolimus and its metabolites that would be ingested by breastfed infants. The mean amount of tacrolimus that would be ingested by the neonates in maternal milk was 151.4 ng/kg/24 h (standard deviation SD � 74.39); metabolite M-1: 23.80 ng/kg/24 h (SD � 14.53); and metabolite M-3: 13.25 ng/kg/24 h (SD � 9.05). The peak level of tacrolimus and metabolite M-1 in colostrum was noted 8 h after an oral dose (3.219 ng/mL SD � 2.22 and 0.56 ng/mL SD � 0.60, respectively) and metabolite M-3 after 6 h (0.29 ng/mL SD � 0.22). Low concentrations of tacrolimus and its metabolites, M-1 and M-3, in colostrum show that neonates will ingest trace amounts of the drug. Further studies are required to fully assess the safety of breastfeeding by posttransplant mothers

Blaski i cienie życia – Perspektywa psychologiczna

Z wprowadzenia: "Książka zatytułowana Blaski i cienie życia – perspektywa psychologiczna wpisuje się w badania dotyczące uwarunkowań zachowania człowieka w wymiarze biologicznym, psychicznym i społecznym. Poszczególne rozdziały tej publikacji powiązane są z różnorodną problematyką, ale mają pewną wspólną właściwość – wszystkie dotyczą psychologicznych problemów życia współczesnego człowieka, jakże złożonych i interesujących z perspektywy badań i praktyki zawodowej."(...

Limited ER quality control for GPI-anchored proteins

Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradation, leading to predictions that a GPI anchor sterically obstructs ERAD. Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast. We could efficiently route Gas1* to Hrd1-dependent ERAD and provide evidence that it contains a GPI anchor, ruling out that a GPI anchor obstructs ERAD. Instead, we show that the normally decreased susceptibility of Gas1* to ERAD is caused by canonical remodeling of its GPI anchor, which occurs in all GPI-APs and provides a protein-independent ER export signal. Thus, GPI anchor remodeling is independent of protein folding and leads to efficient ER export of even misfolded species. Our data imply that ER quality control is limited for the entire class of GPI-APs, many of them being clinically relevant