What's past is prologue: Recalled parenting styles are associated with childhood cancer survivors' mental health outcomes more than 25 years after diagnosis.

BACKGROUND: With the increased survival rates of childhood cancer, long-term survivors' well-being over the life span has come into focus. A better understanding of the determinants of childhood cancer survivors' (CCS) mental health outcomes contributes to the identification of vulnerable individuals as well as to the development of evidence-based prevention and intervention efforts. It has been noted that psychosocial factors such as parental rearing behavior shape individual differences in mental health. There is also evidence that parents show altered parenting behavior in the face of childhood cancer, e. g. that they express more emotional support, but also more worries. However, little is known about the relevance of different parenting styles for CCS' mental health decades after diagnosis and treatment. METHODS: We examined the associations of recalled parenting styles and disease-related factors with lifetime diagnoses of depression and anxiety disorders in a German, registry-based sample of adult CCS (N = 948, 44.50% women) with survival times >25 years. We conducted logistic regression analyses of lifetime diagnoses of depression and anxiety disorders, respectively, on dimensions of recalled parental rearing behavior (measured with a validated German short version of the EMBU) controlling for relevant adjustment variables such as the presence of physical illnesses. RESULTS: Recalled parenting styles of both parents had statistically relevant associations with CCS' lifetime depression and anxiety diagnoses. Maternal emotional warmth was related to fewer lifetime diagnoses of depression and fewer lifetime diagnoses of anxiety. Memories of paternal control and overprotection were positively associated with lifetime diagnoses of anxiety. CONCLUSION: The results indicate that mental representations of one's caregivers are associated with psychological long-term outcomes. Thus, medical professionals should involve the parents and support them in accompanying their child through the difficult times of treatment and survivorship. Interventions aimed at fostering survivors' quality of life should consider the sustained relevance of early relationships.

Parenting in the face of serious illness: Childhood cancer survivors remember different rearing behavior than the general population.

OBJECTIVE: A child's cancer diagnosis and treatment affect the whole family. While it has been recognized that parents are an important resource for their children, little is known about the specifics of parenting in the face of serious illness. METHODS: We used the Recalled Parental Rearing Behavior Questionnaire in a register-based cohort of adult childhood cancer survivors (CCS) (N = 951) and a representative population sample of the same age range (N = 2042). The questionnaire assesses behavior of mothers and fathers with three scales (emotional warmth, rejection/punishment, and control/overprotection) by querying the (former) child. We compared the two groups using general linear models. With a hierarchical linear regression analysis, we tested associations of recalled rearing behavior with disease- and treatment-related factors. RESULTS: Compared with the general population, CCS remembered both parents as emotionally warmer, more overprotective, and less punishing/rejecting and less ambitious. The regression analysis showed that having received radiotherapy (ß = 0.092; P = .009) and chemotherapy (ß = 0.077; P = .027) was positively related to memories of maternal emotional warmth. CONCLUSIONS: CCS remembered parenting styles which are generally deemed more positive. The extent of recalled control and overprotection deviated from the population in different directions, suggesting that parenting in childhood cancer entails more complex adaptations than being affectionate and giving comfort. The results suggest an adaptation of parental behavior to particularly challenging treatments. They highlight potential vulnerability and resilience factors, some of which were sex-dependent.

The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species.

SARS-coronavirus (CoV) is a zoonotic agent derived from rhinolophid bats, in which a plethora of SARS-related, conspecific viral lineages exist. Whereas the variability of virulence among reservoir-borne viruses is unknown, it is generally assumed that the emergence of epidemic viruses from animal reservoirs requires human adaptation. To understand the influence of a viral factor in relation to interspecies spillover, we studied the papain-like protease (PLP) of SARS-CoV. This key enzyme drives the early stages of infection as it cleaves the viral polyprotein, deubiquitinates viral and cellular proteins, and antagonizes the interferon (IFN) response. We identified a bat SARS-CoV PLP, which shared 86% amino acid identity with SARS-CoV PLP, and used reverse genetics to insert it into the SARS-CoV genome. The resulting virus replicated like SARS-CoV in Vero cells but was suppressed in IFN competent MA-104 (3.7-fold), Calu-3 (2.6-fold) and human airway epithelial cells (10.3-fold). Using ectopically-expressed PLP variants as well as full SARS-CoV infectious clones chimerized for PLP, we found that a protease-independent, anti-IFN function exists in SARS-CoV, but not in a SARS-related, bat-borne virus. This PLP-mediated anti-IFN difference was seen in primate, human as well as bat cells, thus independent of the host context. The results of this study revealed that coronavirus PLP confers a variable virulence trait among members of the species SARS-CoV, and that a SARS-CoV lineage with virulent PLPs may have pre-existed in the reservoir before onset of the epidemic.

Expression of CLAVATA3 fusions indicates rapid intracellular processing and a role of ERAD.

The 12 amino acid peptide derived from the Arabidopsis soluble secretory protein CLAVATA3 (CLV3) acts at the cell surface in a signalling system that regulates the size of apical meristems. The subcellular pathway involved in releasing the peptide from its precursor is unknown. We show that a CLV3-GFP fusion expressed in transfected tobacco protoplasts or transgenic tobacco plants has very short intracellular half-life that cannot be extended by the secretory traffic inhibitors brefeldin A and wortmannin. The fusion is biologically active, since the incubation medium of protoplasts from CLV3-GFP-expressing tobacco contains the CLV3 peptide and inhibits root growth. The rapid disappearance of intact CLV3-GFP requires the signal peptide and is inhibited by the proteasome inhibitor MG132 or coexpression with a mutated CDC48 that inhibits endoplasmic reticulum-associated protein degradation (ERAD). The synthesis of CLV3-GFP is specifically supported by the endoplasmic reticulum chaperone endoplasmin in an in vivo assay. Our results indicate that processing of CLV3 starts intracellularly in an early compartment of the secretory pathway and that ERAD could play a regulatory or direct role in the active peptide synthesis.

[Psychological Distress and Acceptance of Violence Legitimizing Masculinity Norms among Adolescents]. / Psychische Belastung und die Akzeptanz von gewaltlegitimierenden Männlichkeitsnormen bei Jugendlichen.

The proportion of adolescent migrants in Germany aged 15-20 years has risen to about 29.5% in 2014 according to Federal census statistics. The purpose of the current study was to describe and to compare the psychological strains of adolescent 1st and 2nd generation migrants with non-migrants in a representative school survey. Acceptance of violence legitimizing masculinity norms was explored and its correlation with psychological strain was analyzed. Self-reported data of psychological strain (internalizing and externalizing problems) and acceptance of violence legitimizing masculinity were gathered among 8 518 pupils aged 12-19 years across different school types. Among the surveyed adolescents, 27.6% reported a migration background (5.8% 1st generation migrants; 21.8% 2nd generation migrants). Particularly 1st generation migrants scored higher in internalizing and externalizing problems than 2nd generation migrants or non-migrants. The differences, however, were small. Adolescents with migration background suffered from educational disadvantage, especially 1st generation migrants. Male adolescents reported significantly higher acceptance of violence legitimizing masculinity norms than their female counterparts. Strong agreement with the measured concept of masculinity was found among pupils of lower secondary school and adolescents reported regularly tobacco and cannabis consumption. The acceptance of violence legitimizing masculinity norms was greater among migrants, particularly 1st generation migrants, than non-migrants. Overall, high acceptance of violence legitimizing masculinity norms was related to externalizing problems, which can be understood as dysfunctional coping mechanisms of social disadvantage and a lack of prospects.

Protein domains involved in assembly in the endoplasmic reticulum promote vacuolar delivery when fused to secretory GFP, indicating a protein quality control pathway for degradation in the plant vacuole.

The correct folding and assembly of newly synthesized secretory proteins are monitored by the protein quality control system of the endoplasmic reticulum (ER). Through interactions with chaperones such as the binding protein (BiP) and other folding helpers, quality control favors productive folding and sorts for degradation defective proteins. A major route for quality control degradation identified in yeast, plants, and animals is constituted by retrotranslocation from the ER to the cytosol and subsequent disposal by the ubiquitin/proteasome system, but alternative routes involving the vacuole have been identified in yeast. In this study, we have studied the destiny of sGFP418, a fusion between a secretory form of GFP and a domain of the vacuolar protein phaseolin that is involved in the correct assembly of phaseolin and in BiP recognition of unassembled subunits. We show that sGFP418, despite lacking the phaseolin vacuolar sorting signal, is delivered to the vacuole and fragmented, in a process that is inhibited by the secretory traffic inhibitor brefeldin A. Moreover, a fusion between GFP and a domain of the maize storage protein gamma-zein involved in zein polymerization also undergoes post-translational fragmentation similar to that of sGFP418. These results show that defective secretory proteins with permanently exposed sequences normally involved in oligomerization can be delivered to the vacuole by secretory traffic. This strongly suggests the existence of a plant vacuolar sorting mechanism devoted to the disposal of defective secretory proteins.

Plant endoplasmin supports the protein secretory pathway and has a role in proliferating tissues.

Endoplasmin is a molecular chaperone of the heat-shock protein 90 class located in the endoplasmic reticulum and its activity is poorly characterized in plants. We assessed the ability of endoplasmin to alleviate stress via its transient overexpression in tobacco protoplasts treated with tunicamycin, an inhibitor of glycosylation and inducer of the unfolded protein response (UPR). Endoplasmin supported the secretion of a model secretory protein but was less effective than BiP, the endoplasmic reticulum member of the heat-shock protein 70 family. Consistently, immunoprecipitation experiments with in vivo radioactively labelled proteins using an antiserum prepared against Arabidopsis endoplasmin showed that a much smaller number of newly synthesized polypeptides associated with endoplasmin than with BiP. Synthesis of endoplasmin was enhanced by UPR inducers in tobacco seedlings but not protoplasts. As BiP synthesis was induced in both systems, we conclude that the UPR acts differently, at least in part, on the expression of the two chaperones. Endoplasmin was not detectable in extracts of leaves and stems of the Arabidopsis endoplasmin T-DNA insertion mutant shepherd. However, the chaperone is present, albeit at low levels, in shepherd mutant callus, mature roots and tunicamycin-treated seedlings, demonstrating that the mutation is leaky. Reduced endoplasmin in the shepherd mutant has no effect on BiP protein levels in callus or mature roots, leaves and stems, but is compensated by increased BiP in seedlings. This increase occurs in proliferating rather than expanding leaf cells, indicating an important role for endoplasmin in proliferating plant tissues.