Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings

The biological basis and clinical significance of hormonal imprinting, an epigenetic process

The biological phenomenon, hormonal imprinting, was named and defined by us (Biol Rev, 1980, 55, 47-63) 30 years ago, after many experimental works and observations. Later, similar phenomena were also named to epigenetic imprinting or metabolic imprinting. In the case of hormonal imprinting, the first encounter between a hormone and its developing target cell receptor—usually at the perinatal period—determines the normal receptor-hormone connection for life. However, in this period, molecules similar to the target hormone (members of the same hormone family, synthetic drugs, environmental pollutants, etc), which are also able to bind to the receptor, provoke faulty imprinting also with lifelong—receptorial, behavioral, etc.,—consequences. Faulty hormonal imprinting could also be provoked later in life in continuously dividing cells and in the brain. Faulty hormonal imprinting is a disturbance of gene methylation pattern, which is epigenenetically inherited to the further generations (transgenerational imprinting). The absence of the normal or the presence of false hormonal imprinting predispose to or manifested in different diseases (e.g., malignant tumors, metabolic syndrome) long after the time of imprinting or in the progenies

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

Nanoparticle Characterization - Supplementary Comparison on Nanoparticle Size

Nanoparticles with size in the range from 10 nm to 300 nm and from three different materials (Au 10 nm, Ag 20 nm, and PSL 30 nm, 100 nm and 300 nm) were used in this supplementary comparison. The selected nanoparticles meet the requirements of different measurement methods such as Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and Differential Mobility Analyzer (DMA), Small Angle X-Ray Scattering and for forth.All 37 participating laboratories returned results, but not all laboratories were able to perform measurement of all 5 nanoparticles.In order to determine the degree of equivalence (DOE), two reference values were considered in this comparison: the method dependent reference value (MRV) and the global reference value (GRV). The MRVs were determined for different measurement methods according to the corresponding reported uncertainties and measurement values from the participants. Each measurement method owns its own MRV. Since the measurement data from DLS were very different from and inconsistent with the measurement data from the other methods, the MRV for DLS was used in the En number calculation for the measurement data reported from the DLS method. The GRV was determined from the MRVs and their uncertainties of all the measurement methods except DLS, and was applied in the En number calculations for the measurement data reported from AFM, EM, DMA and SAXS methods.The assumption that the particles are spherical was commonly made in the nanoparticle measurements. Non-sphericity of particles, if exists, could have different impacts on different measurement methods. It is also important to note that the methods used are measuring mean diameters of a population of particles, not just a single particle, and that the meaning of the mean diameter could differ for different methods. Probably if participants include a different specific contribution in the uncertainty in a harmonized way, taking the non-cancelled method-dependent "systematic" errors into account, it may be easier to compare the results