Hypothalamic Obesity in Patients with Craniopharyngioma: Profound Changes of Several Weight Regulatory Circuits

One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO). This drastic condition is frequently seen in patients with craniopharyngioma (CP), an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight-regulating circuitries

Vitamin D Deficiency in Obese Children and Its Relationship to Insulin Resistance and Adipokines

Low-serum concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with insulin resistance in adults. Less data are available in pediatric populations. Serum 25(OH)D serum concentrations were assessed in 125 obese and 31 nonobese children (age 11.9 ± 2.7 y, range 6–16 y, 49% male) living in Bonn, Germany. The relationship between 25(OH)D, measured by liquid chromatography-tandem mass spectrometry, and measures of insulin sensitivity and adipokines adiponectin and resistin were analyzed. Seventy-six % of subjects were 25(OH)D deficient (<20 ng/mL). Higher insulin, homeostasis model assessment-insulin resistance (HOMA-IR r = −0.269, P = 0.023), and hemoglobin A1c (HbA1c) as well as lower quantitative insulin-sensitivity check index (QUICKI r = 0.264, P = 0.030) values were found in obese children with lower 25(OH)D concentrations even after adjustment for gender, age, and body mass index. Furthermore, 25(OH)D correlated significantly with adiponectin, but not with resistin. Our results suggest that hypovitaminosis D is a risk factor for developing insulin resistance independent of adiposity

The Role of Physical Activity in Nonalcoholic and Metabolic Dysfunction Associated Fatty Liver Disease

Sedentary behavior constitutes a pandemic health threat contributing to the pathophysiology of obesity and type 2 diabetes (T2D). Sedentarism is further associated with liver disease and particularly with nonalcoholic/metabolic dysfunction associated fatty liver disease (NAFLD/MAFLD). Insulin resistance (IR) represents an early pathophysiologic key element of NAFLD/MAFLD, prediabetes and T2D. Current treatment guidelines recommend regular physical activity. There is evidence, that physical exercise has impact on a variety of molecular pathways, such as AMP-activated protein kinase and insulin signaling as well as glucose transporter 4 translocation, modulating insulin action, cellular substrate flow and in particular ectopic lipid and glycogen storage in a positive manner. Therefore, physical exercise can lead to substantial clinical benefit in persons with diabetes and/or NAFLD/MAFLD. However, experience from long term observational studies shows that the patients’ motivation to exercise regularly appears to be a major limitation. Strategies to integrate everyday physical activity (i.e., nonexercise activity thermogenesis) in lifestyle treatment schedules might be a promising approach. This review aggregates evidence on the impact of regular physical activity on selected molecular mechanisms as well as clinical outcomes of patients suffering from IR and NAFLD/MAFLD

Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis

The initiation of mammalian puberty and the maintenance of female reproductive cycles are events controlled by hypothalamic neurons that secrete the decapeptide gonadotropin-releasing hormone (GnRH). GnRH secretion is, in turn, controlled by changes in neuronal and glial inputs to GnRH-producing neurons. The hierarchical control of the process is unknown, but it requires coordinated regulation of these cell-cell interactions. Here we report the functional characterization of a gene (termed enhanced at puberty 1 [EAP1]) that appears to act as an upstream transcriptional regulator of neuronal networks controlling female reproductive function. EAP1 expression increased selectively at puberty in both the nonhuman primate and rodent hypothalamus. EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity. Inhibition of EAP1 expression, targeted to the rodent hypothalamus via lentivirus-mediated delivery of EAP1 siRNAs, delayed puberty, disrupted estrous cyclicity, and resulted in ovarian abnormalities. These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.This work was supported by grants from the NIH, the National Institute of Child Health and Human Development/NIH (to S.R. Ojeda), the European Society for Paediatric Endocrinology (to H. Jung), the German Research Foundation (to S. Heger), and the European Commission (PIONEER to S. Heger)

The organization of interaction design pattern languages alongside the design process

This work explores the possibility of taking the structural characteristics of approaches to interaction design as a basis for the organization of interaction design patterns. The Universal Model of the User Interface (Baxley, 2003) is seen as well suited to this; however, in order to cover the full range of interaction design patterns the model had to be extended slightly. Four existing collections of interaction design patterns have been selected for an analysis in which the patterns have been mapped onto the extended model. The conclusion from this analysis is that the use of the model supports the process of building a pattern language, because it is predictive and helps to complete the language. If several pattern writers were to adopt the model, a new level of synergy could be attained among these pattern efforts. A concluding vision would be that patterns could be transferred freely between pattern collections to make them as complete as possibl

Reflecting on integrated assessment in the Socially Inclusive Agricultural Intensification (SIAGI) project

Agricultural aide interventions are often intended to help small and marginal farmer households increase their agricultural production, and by doing so, better meet their household needs and improve their social and economic standing. However, intensifying their agricultural production requires them to have the capital assets (financial, human, natural, physical and social) and agency to access and use more agricultural inputs, develop and manage the necessary farm or community level infrastructure (e.g. for irrigation, or post-harvesting), and make informed crop and land management choices. Many small and marginalised farmers are lacking in both capital and agency, which constrains their capacity to engage in, and benefit from, agricultural intensification. In this paper, we reflect on our integration research in the 'Promoting Socially Inclusive and sustainable Agricultural Intensification in West Bengal and Bangladesh' (SIAGI) project, focusing on the learnings and outcomes of being socially inclusive in our modelling practices. The Ethical Community Engagement (ECE) ethos and practice to which the SIAGI project team has committed has shaped the content of the integrated assessment frameworks that we have developed as well as the process (Figure 1) we used to develop them. Social inclusion is both a core value of the SIAGI project and an outcome against which the impact of the project will be measured

Integrated assessment frameworks for understanding pathways for socially inclusive agricultural intensification

Alleviating poverty through agricultural development is a challenge that requires sound understanding of the social, market, environmental and institutional settings. An integrated assessment (IA) process can help to clarify and examine the nature of the interactions between these diverse processes and facilitate concerted and collaborative efforts from interdisciplinary teams. This paper provides an overview of IA frameworks developed for a project aimed at identifying opportunities and policy options that promote more socially inclusive and sustainable agricultural intensification in rural communities in West Bengal and Bangladesh. The IA frameworks were intended to provide a 'big picture' of the social and agricultural systems we are researching, and to improve understanding of the interrelationships between the diverse processes, and the pathways between drivers and outcomes. This paper describes the methodological process followed in developing these frameworks (Figure 1). The frameworks are grounded in both theory and observations from project activities, and were iteratively developed with input from stakeholders and domain experts. The frameworks then formed the basis for further (semi)quantitative or qualitative analysis, demonstrated in the study through the development of semi-quantitative models (fuzzy cognitive maps) and narratives.This project (LWR/2014/072) is funded by the Australian Centre for International Agricultural Research (ACIAR). The authors acknowledge contributions from all members of the SIAGI project team

Great Cause—Small Effect: Undeclared Genetically Engineered Orange Petunias Harbor an Inefficient Dihydroflavonol 4-Reductase

A recall campaign for commercial, orange flowering petunia varieties in spring 2017 caused economic losses worldwide. The orange varieties were identified as undeclared genetically engineered (GE)-plants, harboring a maize dihydroflavonol 4-reductase (DFR, A1), which was used in former scientific transgenic breeding attempts to enable formation of orange pelargonidin derivatives from the precursor dihydrokaempferol (DHK) in petunia. How and when the A1 cDNA entered the commercial breeding process is unclear. We provide an in-depth analysis of three orange petunia varieties, released by breeders from three countries, with respect to their transgenic construct, transcriptomes, anthocyanin composition, and flavonoid metabolism at the level of selected enzymes and genes. The two possible sources of the A1 cDNA in the undeclared GE-petunia can be discriminated by PCR. A special version of the A1 gene, the A1 type 2 allele, is present, which includes, at the 3′-end, an additional 144 bp segment from the non-viral transposable Cin4-1 sequence, which does not add any functional advantage with respect to DFR activity. This unequivocally points at the first scientific GE-petunia from the 1980s as the A1 source, which is further underpinned e.g., by the presence of specific restriction sites, parts of the untranslated sequences, and the same arrangement of the building blocks of the transformation plasmid used. Surprisingly, however, the GE-petunia cannot be distinguished from native red and blue varieties by their ability to convert DHK in common in vitro enzyme assays, as DHK is an inadequate substrate for both the petunia and maize DFR. Recombinant maize DFR underpins the low DHK acceptance, and, thus, the strikingly limited suitability of the A1 protein for a transgenic approach for breeding pelargonidin-based flower color. The effect of single amino acid mutations on the substrate specificity of DFRs is demonstrated. Expression of the A1 gene is generally lower than the petunia DFR expression despite being under the control of the strong, constitutive p35S promoter. We show that a rare constellation in flavonoid metabolism—absence or strongly reduced activity of both flavonol synthase and B-ring hydroxylating enzymes—allows pelargonidin formation in the presence of DFRs with poor DHK acceptance.Peer Reviewe

Resolution of the type material of the Asian elephant, Elephas maximus Linnaeus, 1758 (Proboscidea, Elephantidae)

The understanding of Earth’s biodiversity depends critically on the accurate identification and nomenclature of species. Many species were described centuries ago, and in a surprising number of cases their nomenclature or type material remain unclear or inconsistent. A prime example is provided by Elephas maximus, one of the most iconic and well-known mammalian species, described and named by Linnaeus (1758) and today designating the Asian elephant. We used morphological, ancient DNA (aDNA), and high-throughput ancient proteomic analyses to demonstrate that a widely discussed syntype specimen of E. maximus, a complete foetus preserved in ethanol, is actually an African elephant, genus Loxodonta. We further discovered that an additional E. maximus syntype, mentioned in a description by John Ray (1693) cited by Linnaeus, has been preserved as an almost complete skeleton at the Natural History Museum of the University of Florence. Having confirmed its identity as an Asian elephant through both morphological and ancient DNA analyses, we designate this specimen as the lectotype of E. maximus

From gradual spreading to catastrophic collapse - Reconstruction of the 1888 Ritter Island volcanic sector collapse from high-resolution 3D seismic data

Volcanic island flank collapses have the potential to trigger devastating tsunamis threatening coastal communities and infrastructure. The 1888 sector collapse of Ritter Island, Papua New Guinea (in the following called Ritter) is the most voluminous volcanic island flank collapse in historic times. The associated tsunami had run-up heights of more than 20 m on the neighboring islands and reached settlements 600 km away from its source. This event provides an opportunity to advance our understanding of volcanic landslide-tsunami hazards. Here, we present a detailed reconstruction of the 1888 Ritter sector collapse based on high-resolution 2D and 3D seismic and bathymetric data covering the failed volcanic edifice and the associated mass-movement deposits. The 3D seismic data reveal that the catastrophic collapse of Ritter occurred in two phases: (1) Ritter was first affected by deep-seated, gradual spreading over a long time period, which is manifest in pronounced compressional deformation within the volcanic edifice and the adjacent seafloor sediments. A scoria cone at the foot of Ritter acted as a buttress, influencing the displacement and deformation of the western flank of the volcano and causing shearing within the volcanic edifice. (2) During the final, catastrophic phase of the collapse, about 2.4 km³ of Ritter disintegrated almost entirely and travelled as a highly energetic mass flow, which incised the underlying sediment. The irregular topography west of Ritter is a product of both compressional deformation and erosion. A crater-like depression underlying the recent volcanic cone and eyewitness accounts suggest that an explosion may have accompanied the catastrophic collapse. Our findings demonstrate that volcanic sector collapses may transform from slow gravitational deformation to catastrophic collapse. Understanding the processes involved in such a transformation is crucial for assessing the hazard potential of other volcanoes with slowly deforming flanks such as Mt. Etna or Kilauea