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\"This book presents recent advancements in positive psychology, specifically its application across broad areas of current interest. Chapters include submissions from various international authors in the field and cover discussion and presentation of relevant research, theories, and applications. The volume covers topics such as CBT, Psychotherapy, Coaching, Workplaces, Aging, Education, Leadership, Emotion, Interventions, Measurement, Technology, Design, Health, Relationships, Experiences, Communities. With the growing interest in the applications of positive psychology across diverse fields within psychology and beyond, this book will make a worthwhile contribution to the field. It will also fill the current need for a volume that highlights specifically the various recent advancements in positive psychology into diverse fields and as such will be of benefit to a wide range of professionals, including psychologists, educators, clinicians, therapists, and many others.\" -- Publisher's website.

Hybrid semiconductor–superconductor devices hold great promise for realizing topological quantum computing with Majorana zero modes 1 – 5 . However, multiple claims of Majorana detection, based on either tunnelling 6 – 10 or Coulomb blockade (CB) spectroscopy 11 , 12 , remain disputed. Here we devise an experimental protocol that allows us to perform both types of measurement on the same hybrid island by adjusting its charging energy via tunable junctions to the normal leads. This method reduces ambiguities of Majorana detections by checking the consistency between CB spectroscopy and zero-bias peaks in non-blockaded transport. Specifically, we observe junction-dependent, even–odd modulated, single-electron CB peaks in InAs/Al hybrid nanowires without concomitant low-bias peaks in tunnelling spectroscopy. We provide a theoretical interpretation of the experimental observations in terms of low-energy, longitudinally confined island states rather than overlapping Majorana modes. Our results highlight the importance of combined measurements on the same device for the identification of topological Majorana zero modes. Valentini et al. devise a method through which they can perform both tunnelling spectroscopy and Coulomb blockade spectroscopy on the same hybrid nanowire island to reduce ambiguities in the detection of Majorana.

We analyzed the depth distributions of benthic diatoms in two adjacent, but hydrologically distinct subalpine lakes (Lakes Soiernseen, S-Germany). Lake Unterer Soiernsee is affected by marked water-level fluctuations and is light-penetrated to the bottom most of the year, while Lake Oberer Soiernsee provides more stable conditions and an extended aphotic zone. Mixed samples of epiphytic, epilithic, epipsammic and epipelic periphyton were taken in one-meter depth steps by scuba divers. Most of the common benthic diatoms occurred in distinct depth-areas. RDA analyses showed that depth was strongly correlated with species distribution in both lakes. Depth-constrained cluster analyses indicated three distinct diatom community zones in each lake. A shallow littoral zone hosting mainly epiphytic and epilithic species and a deeper littoral zone with mainly epipsammic and epipelic taxa existed in both lakes. Additionally, a highly disturbed near-shore littoral zone with diatoms adapted to unstable conditions (aerophilic taxa, pioneer species) was found in Lake Unterer Soiernsee, and a deep-water pelagic zone with mainly planktonic taxa in Lake Oberer Soiernsee. Light availability, substrate, physical stressors and nutrient concentrations were linked closely with water depth. While light availability affected the ratio of benthic and planktonic diatoms, substrate type influenced benthic diatom assemblage structures. Diatoms occurring in surficial sediments of the aphotic zone represent an ideal cross-section of the recent diatom assemblage of the lake, including benthic and planktonic species. However, sediment samples taken in light-flooded depths are inappropriate for studies based on shifts between benthic and planktonic taxa, because in situ benthic species dominate the surface-sediment assemblages, while settled tychoplanktonic and planktonic species occur less frequently. A diatom-inferred depth model was created for each lake to prove the usability for down-core studies using weighted-averaging approaches. For both lakes these models are highly appropriate to reconstruct past fluctuations in water-transparency or lake-level. With regard to the development of diatom-based TP-transfer-functions for Bavarian mountain lakes, we found it is highly important to consider lake depth and transparency. Based on the findings of this study we recommend the creation of two different training-sets, one for deep or low-transparency lakes with an aphotic zone including both benthic and planktonic diatoms, and another one for shallow, clear water lakes solely using benthic diatoms.

The Speech-to-Speech Synchronization task is a well-established behavioral approach to assess individual differences in auditory-motor synchronization. In this task, participants listen to a series of syllables that progressively increase in frequency, while simultaneously whispering the syllable /ta/ to synchronize with the rhythm of the incoming syllables. In our study, we replicated the bimodal distribution of high- and low-synchronizers in a sample of native German speakers. We present a refined analysis pipeline based on existing analysis scripts, address minor task-related issues and observations, and incorporate new analysis features such as the removal of silent gaps. Crucially, our analysis revealed that (sub-)harmonic interactions can emerge during various stages of synchronization and its assessment, obscured by the synchronization measurement. Subharmonic synchronizers were found to produce the /ta/-syllables to only every second or third incoming syllable which can result in deceptively high Phase Locking Values, thus challenging the conceptualization of low- and high-synchronizers. Our data analysis is available at OSF .

Mountain lakes are increasingly impacted by a series of both local and global disturbances. The present study reveals the eutrophication history of a remote subalpine lake (Oberer Soiernsee, Northern Alps, Germany), triggered by deforestation, alpine pasturing, hut construction, tourism and atmospheric deposition, and identifies the intertwined consequences of on-going global warming on the lake’s ecosystem. The primary objective was to disentangle the various direct and indirect impacts of these multiple stressors via down-core analyses. Our multi-proxy approach included subfossil diatom assemblages, carbon and nitrogen stable isotope ratios and subfossil pigments from dated sediments. Shifts within the diatom assemblages were related to variations in trophic state, lake transparency, water temperature and thermal stratification. The organic carbon isotope (δ13Corg) records, the diatom valve density and the pigment concentrations documented the development of primary production and composition. Total nitrogen isotope values (δ15N) are more likely to reflect the history of atmospheric nitrogen pollution than lake-internal processes, also mirrored by the decoupling of δ15N and δ13Corg trends. The composition of sedimentary pigments allowed a differentiation between planktonic and benthic primary production. Concordant trends of all indicators suggested that the lake ecosystem passed a climatic threshold promoted by local and long-distance atmospheric nutrient loadings.

Type II germ cell cancers (GCC) can be subdivided into seminomas and non-seminomas. Seminomas are similar to carcinoma in situ (CIS) cells, the common precursor of type II GCCs, with regard to epigenetics and expression, while embryonal carcinomas (EC) are totipotent and differentiate into teratomas, yolk-sac tumors and choriocarcinomas. GCCs can present as seminomas with a non-seminoma component, raising the question if a CIS gives rise to seminomas and ECs at the same time or whether seminomas can be reprogrammed to ECs. In this study, we utilized the seminoma cell line TCam-2 that acquires an EC-like status after xenografting into the murine flank as a model for a seminoma to EC transition and screened for factors initiating and driving this process. Analysis of expression and DNA methylation dynamics during transition of TCam-2 revealed that many pluripotency- and reprogramming-associated genes were upregulated while seminoma-markers were downregulated. Changes in expression level of 53 genes inversely correlated to changes in DNA methylation. Interestingly, after xenotransplantation 6 genes (GDF3, NODAL, DNMT3B, DPPA3, GAL, AK3L1) were rapidly induced, followed by demethylation of their genomic loci, suggesting that these 6 genes are poised for expression driving the reprogramming. We demonstrate that inhibition of BMP signaling is the initial event in reprogramming, resulting in activation of the pluripotency-associated genes and NODAL signaling. We propose that reprogramming of seminomas to ECs is a multi-step process. Initially, the microenvironment causes inhibition of BMP signaling, leading to induction of NODAL signaling. During a maturation phase, a fast acting NODAL loop stimulates its own activity and temporarily inhibits BMP signaling. During the stabilization phase, a slow acting NODAL loop, involving WNTs re-establishes BMP signaling and the pluripotency circuitry. In parallel, DNMT3B-driven de novo methylation silences seminoma-associated genes and epigenetically fixes the EC state.

Current perspectives on the molecular underpinnings of major depressive disorder (MDD) posit a mechanistic role of epigenetic DNA modifications in mediating the interaction between environmental risk factors and a genetic predisposition. However, conclusive evidence for differential methylation signatures in the brain’s epigenome of MDD patients as compared to controls is still lacking. To address this issue, we conducted a pilot study including an epigenome-wide methylation analysis in six individuals diagnosed with recurrent MDD and six control subjects matched for age and gender, with a priori focus on the hippocampus and prefrontal cortex as pathophysiologically relevant candidate regions. Our analysis revealed differential methylation profiles of 11 genes in hippocampus and 20 genes in prefrontal cortex, five of which were selected for replication of the methylation status using pyrosequencing. Among these replicated targets, GRIN2A was found to be hypermethylated in both prefrontal cortex and hippocampus. This finding may be of particular functional relevance as GRIN2A encodes the glutamatergic N -methyl- d -aspartate receptor subunit epsilon-1 (NR2A) and is known to be involved in a plethora of synaptic plasticity-related regulatory processes probably disturbed in MDD.

Malaria ranks among the most important infectious diseases worldwide and affects mostly people living in tropical countries. Mechanisms involved in disease progression are still not fully understood and specific treatments that might interfere with cerebral malaria (CM) are limited. Here we show that administration of doxycycline (DOX) prevented experimental CM (ECM) in Plasmodium berghei ANKA (PbA)-infected C57BL/6 wildtype (WT) mice in an IL-10-independent manner. DOX-treated mice showed an intact blood-brain barrier (BBB) and attenuated brain inflammation. Importantly, if WT mice were infected with a 20-fold increased parasite load, they could be still protected from ECM if they received DOX from day 4-6 post infection, despite similar parasitemia compared to control-infected mice that did not receive DOX and developed ECM. Infiltration of T cells and cytotoxic responses were reduced in brains of DOX-treated mice. Analysis of brain tissue by RNA-array revealed reduced expression of chemokines and tumour necrosis factor (TNF) in brains of DOX-treated mice. Furthermore, DOX-administration resulted in brains of the mice in reduced expression of matrix metalloproteinase 2 (MMP2) and granzyme B, which are both factors associated with ECM pathology. Systemic interferon gamma production was reduced and activated peripheral T cells accumulated in the spleen in DOX-treated mice. Our results suggest that DOX targeted inflammatory processes in the central nervous system (CNS) and prevented ECM by impaired brain access of effector T cells in addition to its anti-parasitic effect, thereby expanding the understanding of molecular events that underlie DOX-mediated therapeutic interventions.

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.

The oomycete Phytophthora infestans causes late blight of potato, which can completely destroy the crop. Therefore, for the past 160 years, late blight has been the most important potato disease worldwide. The identification of cultivars with high and durable field resistance to P. infestans is an objective of most potato breeding programs. This type of resistance is polygenic and therefore quantitative. Its evaluation requires multi-year and location trials. Furthermore, quantitative resistance to late blight correlates with late plant maturity, a negative agricultural trait. Knowledge of the molecular genetic basis of quantitative resistance to late blight not compromised by late maturity is very limited. It is however essential for developing diagnostic DNA markers that facilitate the efficient combination of superior resistance alleles in improved cultivars. We used association genetics in a population of 184 tetraploid potato cultivars in order to identify single nucleotide polymorphisms (SNPs) that are associated with maturity corrected resistance (MCR) to late blight. The population was genotyped for almost 9000 SNPs from three different sources. The first source was candidate genes specifically selected for their function in the jasmonate pathway. The second source was novel candidate genes selected based on comparative transcript profiling (RNA-Seq) of groups of genotypes with contrasting levels of quantitative resistance to P. infestans. The third source was the first generation 8.3k SolCAP SNP genotyping array available in potato for genome wide association studies (GWAS). Twenty seven SNPs from all three sources showed robust association with MCR. Some of those were located in genes that are strong candidates for directly controlling quantitative resistance, based on functional annotation. Most important were: a lipoxygenase (jasmonate pathway), a 3-hydroxy- 3-methylglutaryl coenzyme A reductase (mevalonate pathway), a P450 protein (terpene biosynthesis), a transcription factor and a homolog of a major gene for resistance to P. infestans from the wild potato species Solanum venturii. The candidate gene approach and GWAS complemented each other as they identified different genes. The results of this study provide new insight in the molecular genetic basis of quantitative resistance in potato and a toolbox of diagnostic SNP markers for breeding applications.