Regulation of genes involved in carnitine homeostasis by PPARa across different species (rat, mouse, pig, cattle, chicken, and human)

Recent studies in rodents convincingly demonstrated that PPAR-alpha is a key regulator of genes involved in carnitine homeostasis, which serves as a reasonable explanation for the phenomenon that energy deprivation and fibrate treatment, both of which cause activation of hepatic PPAR-alpha, causes a strong increase of hepatic carnitine concentration in rats. The present paper aimed to comprehensively analyse available data from genetic and animal studies with mice, rats, pigs, cows, and laying hens and from human studies in order to compare the regulation of genes involved in carnitine homeostasis by PPAR-alpha across different species. Overall, our comparative analysis indicates that the role of PPAR-alpha as a regulator of carnitine homeostasis is well conserved across different species. However, despite demonstrating a well-conserved role of PPAR-alpha as a key regulator of carnitine homeostasis in general, our comprehensive analysis shows that this assumption particularly applies to the regulation by PPAR-alpha of carnitine uptake which is obviously highly conserved across species, whereas regulation by PPAR-alpha of carnitine biosynthesis appears less well conserved across species

Introducing zanadio: A digitalized, multimodal program to treat obesity

While the prevalence of overweight and obesity has been increasing annually, the accessibility of on-site treatment programs is not rising correspondingly. Digital, evidence-based obesity treatment programs could potentially alleviate this situation. The application zanadio has been developed to enable patients with obesity (BMI 30-45 kg/m2) to participate in a digital, multimodal weight reduction program based on current treatment guidelines. This article is divided into two parts: (I) it introduces zanadio, its aims and therapeutic concept, and (II) provides a first impression and demographic data on more than 11,000 patients from across the country who have used zanadio within the last 16 months, which demonstrates the demand for a digital obesity treatment. zanadio has the potential to partially close the current gap in obesity care. Future work should focus on identifying predictors of successful weight loss to further individualize digital obesity treatment, and an important next step would be to prevent obesity, i.e., to start the treatment at lower BMI levels, and to invent digital treatment programs for children and adolescents

Comprehensive metabolite profiling of Plantaginis Semen using ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry coupled with elevated energy technique

Plantaginis Semen is commonly used in traditional medicine to treat edema, hypertension, and diabetes. The commercially available Plantaginis Semen in China mainly comes from three species. To clarify the chemical composition and distinct different species of Plantaginis Semen, we established a metabolite profiling method based on ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry coupled with elevated energy technique. A total of 108 compounds, including phenylethanoid glycosides, flavonoids, guanidine derivatives, terpenoids, organic acids, and fatty acids, were identified from Plantago asiatica L., P. depressa Willd., and P. major L. Results showed significant differences in chemical components among the three species, particularly flavonoids. This study is the first to provide a comprehensive chemical profile of Plantaginis Semen, which could be involved into the quality control, medication guide, and developing new drug of Plantago seeds

Forgetting to remember? Prospective memory within the context of pain

Pain interferes with cognitive functioning in several ways. Among other symptoms, pain patients often report difficulties with remembering future intentions. It remains unclear, however, whether it is the pain per se that impairs prospective remembering or other factors that often characterize people with pain (e.g. poor sleep quality). In this experiment, we investigated whether prospective memory is impaired within the context of pain, and whether this impairment is enhanced when the threat value of pain is increased.status: publishe

Neural underpinnings of preferential pain learning and the modulatory role of fear

Due to its unique biological relevance, pain-related learning might differ from learning from other aversive experiences. This functional magnetic resonance imaging study compared neural mechanisms underlying the acquisition and extinction of different threats in healthy humans. We investigated whether cue-pain associations are acquired faster and extinguished slower than cue associations with an equally unpleasant tone. Additionally, we studied the modulatory role of stimulus-related fear. Therefore, we used a differential conditioning paradigm, in which somatic heat pain stimuli and unpleasantness-matched auditory stimuli served as US. Our results show stronger acquisition learning for pain- than tone-predicting cues, which was augmented in participants with relatively higher levels of fear of pain. These behavioral findings were paralleled by activation of brain regions implicated in threat processing (insula, amygdala) and personal significance (ventromedial prefrontal cortex). By contrast, extinction learning seemed to be less dependent on the threat value of the US, both on the behavioral and neural levels. Amygdala activity, however, scaled with pain-related fear during extinction learning. Our findings on faster and stronger (i.e. “preferential”) pain learning and the role of fear of pain are consistent with the biological relevance of pain and may be relevant to the development or maintenance of chronic pain

Examining heterogeneity in the affect-regulating function of suicidal ideation: Person-specific analyses in male inpatients with depression

IntroductionMen have an increased risk to die by suicide compared to women but are underrepresented in suicide research. To improve individual risk prediction for suicide-related thoughts and behaviors (STBs), risk factors are increasingly being studied at an individual level. The possible affect-regulatory function of suicidal ideation has hardly been investigated ideographically and has not yet been tested in a male sample.MethodsWe investigated the bidirectional associations between suicidal ideation and negative and positive affect in a sample of n = 21 male inpatients with unipolar depression and a history of suicidal ideation both at the group level and at the individual level. Participants underwent an intensive ecological momentary assessment for 6 days with 10 data points per day.ResultsWe found no evidence for an affect-regulatory function of suicidal ideation at the group level, neither for effects of affect on subsequent suicidal ideation (antecedent affect-regulatory hypothesis) nor for effects of suicidal ideation on subsequent affect (consequence affect-regulatory hypothesis). Person-specific analyses revealed substantial variability in strength and direction of the considered associations, especially for the associations representing the antecedent hypothesis.ConclusionThe demonstrated between-person heterogeneity points to the necessity to individualize the investigation of risk factors to enhance prediction and prevention of STBs

Influence of Cue Exposure on Inhibitory Control and Brain Activation in Patients with Alcohol Dependence

Alcohol dependence is a serious condition characterized by persistent desires to drink and unsuccessful efforts to control alcohol consumption despite the knowledge of dysfunction through the usage. The study at hand examined the influence of an alcohol exposure on inhibitory processes. Research provides evidence that trying to resist the temptation to drink exerts self-control, a limited resource which is used during all acts of inhibition. In line with this, studies demonstrate an impaired ability to regulate an already initiated response in alcohol-dependent and healthy subjects when confronted with alcohol-related stimuli. The related neuronal correlates in alcohol-dependent patients remain to be elucidated. The inhibition performance of 11 male alcohol-dependent patients during an alcohol exposure was compared with the task performance during a control condition. Behavioral data and neural brain activation during task performance were acquired by means of functional magnetic resonance imaging. The alcohol cue exposure led to subjectively stronger urges to drink which was accompanied by differential neural activation in amygdala and hippocampus. Moreover, the results revealed typical neural activation during inhibition performance across both conditions. Anyhow, we could not detect any behavioral deficits and only subtle neural differences between induction conditions during the performance of the inhibition task within the inferior frontal cortex. The results suggest that although the sample reports a subjectively stronger urge to drink after the alcohol cue exposure this effect was not strong enough to significantly impair task performance. Coherently, we discover only subtle differential brain activation between conditions during the inhibition task. In opposition to findings in literature our data do not reveal that an exposure to alcohol-related cues and thereby elicited cue reactivity results in impaired inhibition abilities

Advances in Pathway Engineering for Natural Product Biosynthesis

Biocatalysts provide an efficient, inexpensive and environmentally friendly alternative to traditional organic synthesis, especially for compounds with complex stereochemistries. The past decade has seen a significant rise in the use of biocatalysts for the synthesis of compounds in an industrial setting; however, the incorporation of single enzymatically catalysed steps into organic synthesis schemes can be problematic. The emerging field of synthetic biology has sparked interest in the development of whole-cell factories that can convert simple, common metabolites into complex, high-value molecules with a range of applications such as pharmaceuticals and biofuels. This Review summarises conventional methods and recent advances in metabolic engineering of pathways in microorganisms for the synthesis of natural products