[Nutrition, metabolism, brain and mental health]. / Ernährung, Stoffwechsel, Gehirn und mentale Gesundheit.

This review article explores the intricate relationship between nutrition, metabolism, brain function and mental health. It highlights two key complementary models: the energy balance model and the more comprehensive carbohydrate-insulin model, to understand the development of obesity and metabolic dysfunctions. It particularly focuses on the role of dopamine in dietary regulation and insulin in the brain, both of which are crucial in the pathogenesis of neurodegenerative and stress-associated mental disorders. Additionally, the significance of sleep and dietary habits, such as medically assisted calorie restriction for mental health and the concept of "brain food" are described. These findings emphasize the importance of nutritional medicine in psychiatry and psychotherapy and the consideration of metabolic states for the prevention and treatment of mental and neurodegenerative diseases.

Comparative single cell analysis reveals complex patterns of cell type and cell signaling innovations at the fetal-maternal interface.

The decidual-placental interface is one of the most diverse and rapidly evolving tissues in mammals. Its origin as a chimeric fetal-maternal tissue poses a unique evolutionary puzzle. We present single-cell RNA sequencing atlases from the fetal-maternal interfaces of the opossum, a marsupial, the Malagasy common tenrec, an afrotherian with primitive reproductive features, and mouse, guinea pig, and human. Invasive trophoblast shares a common transcriptomic signature across eutherians, which we argue represents a cell type family that radiated following the evolution of hemochorial placentation. We find evidence that the eutherian decidual stromal cell evolved stepwise from a predecidual state retained in Tenrec , followed by a second decidual cell type originating in Boreoeutheria with endocrine characteristics. We reconstruct ligand-receptor signaling to test evolutionary hypotheses at scale. Novel trophoblast and decidual cell types display strong integration into signaling networks compared to other cells. Additionally, we find consistent disambiguation between fetal and maternal signaling. Using phylogenetic analysis, we infer the cell-cell signaling network of the Placental common ancestor, and identify increased rates of signaling evolution in Euarchontoglires. Together, our findings reveal novel cell type identities and cell signaling dynamics at the mammalian fetal-maternal interface.

Reading the palimpsest of cell interactions: What questions may we ask of the data?

Biological function depends on the composition and structure of the organism, the latter describing the organization of interactions between parts. While cells in multicellular organisms are capable of a remarkable degree of autonomy, most functions do require cell communication: the coordination of functions (growth, differentiation, and apoptosis), the compartmentalization of cellular processes, and the integration of cells into higher levels of structural organization. A wealth of data on putative cell interactions has become available, yet its biological interpretation depends on our expectations about the structure of interaction networks. Here, we attempt to formulate basic questions to ask when interpreting cell interaction data. We build on the understanding that cells fulfill two general functions: the integrity-maintaining and the organismal service function. We derive the expected patterns of cell interactions considering two intertwined aspects: the functional and the evolutionary. Based on these, we propose guidelines for analysis and interpretation of transcriptional cell-interactome data.

Variability in Body Shape, Superficial Soft Tissue Geometry, and Seatbelt Fit Relative to the Pelvis in Automotive Postures-Methods for Volunteer Data Collection With Open Magnetic Resonance Imaging.

Variability in body shape and soft tissue geometry have the potential to affect the body's interaction with automotive safety systems. In this study, we developed a methodology to capture information on body shape, superficial soft tissue geometry, skeletal geometry, and seatbelt fit relative to the skeleton-in automotive postures-using Open Magnetic Resonance Imaging (MRI). Volunteer posture and belt fit were first measured in a vehicle and then reproduced in a custom MRI-safe seat (with an MR-visible seatbelt) placed in an Open MR scanner. Overlapping scans were performed to create registered three-dimensional reconstructions spanning from the thigh to the clavicles. Data were collected with ten volunteers (5 female, 5 male), each in their self-selected driving posture and in a reclined posture. Examination of the MRIs showed that in the males with substantial anterior abdominal adipose tissue, the abdominal adipose tissue tended to overhang the pelvis, narrowing in the region of the Anterior Superior Iliac Spine (ASIS). For the females, the adipose tissue depth around the lower abdomen and pelvis was more uniform, with a more continuous layer superficial to the ASIS. Across the volunteers, the pelvis rotated rearward by an average of 62% of the change in seatback angle during recline. In some cases, the lap belt drew nearer to the pelvis as the volunteer reclined (as the overhanging folds of adipose tissue stretched). In others, the belt-to-pelvis distance increased as the volunteer reclined. These observations highlight the importance of considering both interdemographic and intrademographic variability when developing tools to assess safety system robustness.

Experimental and phylogenetic evidence for correlated gene expression evolution in endometrial and skin fibroblasts.

Gene expression change is a dominant mode of evolution. Mutations, however, can affect gene expression in multiple cell types. Therefore, gene expression evolution in one cell type can lead to similar gene expression changes in another cell type. Here, we test this hypothesis by investigating dermal skin fibroblasts (SFs) and uterine endometrial stromal fibroblasts (ESFs). The comparative dataset consists of transcriptomes from cultured SF and ESF of nine mammalian species. We find that evolutionary changes in gene expression in SF and ESF are highly correlated. The experimental dataset derives from a SCID mouse strain selected for slow cancer growth leading to substantial gene expression changes in SFs. We compared the gene expression profiles of SF with that of ESF and found a significant correlation between them. We discuss the implications of these findings for the evolutionary correlation between placental invasiveness and vulnerability to metastatic cancer.

Caprylic acid attenuates amyloid-ß proteotoxicity by supplying energy via ß-oxidation in an Alzheimer's disease model of the nematode Caenorhabditis elegans.

Computer-based analysis of motility was used as a measure of amyloid-ß (Aß) proteotoxicity in the transgenic strain GMC101, expressing human Aß1-42 in body wall muscle cells. Aß-aggregation was quantified to relate the effects of caprylic acid (CA) to the amount of the proteotoxic protein. Gene knockdowns were induced through RNA-interference (RNAi). Moreover, the estimation of adenosine triphosphate (ATP) levels, the mitochondrial membrane potential (MMP) and oxygen consumption served the evaluation of mitochondrial function. CA improved the motility of GMC101 nematodes and reduced Aß aggregation. Whereas RNAi for orthologues encoding key enzymes for α-lipoic acid and ketone bodies synthesis did not affect motility stimulation by CA, knockdown of orthologues involved in ß-oxidation of fatty acids diminished its effects. The efficient energy gain by application of CA was finally proven by the increase of ATP levels in association with increased oxygen consumption and MMP. In conclusion, CA attenuates Aß proteotoxicity by supplying energy via FAO. Since especially glucose oxidation is disturbed in Alzheimer´s disease, CA could potentially serve as an alternative energy fuel.

Age-related changes in energy metabolism in peripheral mononuclear blood cells (PBMCs) and the brains of cognitively healthy seniors.

Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1H- and 31P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (- 15%) and ATP levels (- 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (- 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (- 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant.

Injury comparisons between paired drivers and front-seat passengers in frontal collisions using publicly available crash and injury data.

Forensic engineers and crash safety researchers sometimes use the injuries of a seatbelted occupant to infer the injury risk of an unbelted occupant in the same crash, had they instead been wearing a seatbelt. It is unclear, however, whether this inference is valid or how often two occupants in the same collision have similar injuries. Here, we sought to compare the injury outcomes between drivers and front-seat passengers in frontal collisions using real-world collision data. We compared the injury severity, quantified using the Abbreviated Injury Scale (AIS), of 22 injury categories between front-seat occupants with matching seatbelt use and airbag deployment in single-event frontal collisions recorded in the publicly available National Automotive Sampling System, Crashworthiness Data System (years 1993-2015) database to assess whether they had similar severity injuries. We analyzed the four combinations of seatbelt use and airbag deployment and all seatbelt/airbag conditions combined. In only 3 of 88 combinations of injuries and seatbelt/airbag conditions did more than 50% of occupant pairs have the same AIS score, although the related confidence intervals showed these proportions were not significantly greater than 50%. In contrast, we found 19 combinations of injuries and seatbelt/airbag conditions where one occupant was consistently injured more severely than the other. Our findings show that injury outcome is not similar for both front-seat occupants in the same frontal collision with similar seatbelt and airbag conditions; however, one may be able to predict that one occupant would be more severely injured than their fellow occupant.

Capturing Head Impacts in Boxing: A Video-Based Comparison of Three Wearable Sensors.

Wearable sensors are used to quantify head impacts in athletes, but recent work has shown that the number of events recorded may not be accurate. This study aimed to compare the number of head acceleration events recorded by three wearable sensors during boxing and assess how impact type and location affect the triggering of acceleration events. Seven boxers were equipped with an instrumented mouthguard, a skin patch, and a headgear patch. Contacts to participants' heads were identified via three video cameras over 115 sparring rounds. The resulting 5168 video-identified events were used as reference to quantify the sensitivity, specificity, and positive predictive value (PPV) of the sensors. The mouthguard, skin patch, and headgear patch recorded 695, 1579, and 1690 events, respectively, yielding sensitivities of 35%, 86%, and 78%, respectively, and specificities of 90%, 76%, and 75%, respectively. The mouthguard, skin patch, and headgear patch yielded 693, 1571, and 1681 true-positive events, respectively, leading to PPVs for head impacts over 96%. All three sensors were more likely to be triggered by punches landing near the sensor and cleanly on the head, although the mouthguard's sensitivity to impact location varied less than the patches. While the use of head impact sensors for assessing injury risks remains uncertain, this study provides valuable insights into the capabilities and limitations of these sensors in capturing video-verified head impact events.

Cryopreservation and Bioenergetic Evaluation of Human Peripheral Blood Mononuclear Cells.

The physiological functions of eukaryotic cells rely on energy mainly provided by mitochondria. Mitochondrial dysfunction is linked to metabolic diseases and aging. Oxidative phosphorylation plays a decisive role, as it is crucial for the maintenance of energetic homeostasis. PBMCs have been identified as a minimally invasive sample to measure mitochondrial function and have been shown to reflect disease conditions. However, measurement of mitochondrial bioenergetic function can be limited by several factors in human samples. Limitations are the amount of samples taken, sampling time, which is often spread over several days, and locations. Cryopreservation of the collected samples can ensure consistent collection and measurement of samples. Care should be taken to ensure that the parameters measured are comparable between cryopreserved and freshly prepared cells. Here, we describe methods for isolating and cryopreserving PBMCs from human blood samples to analyze the bioenergetic function of the mitochondria in these cells. PBMC cryopreserved according to the protocol described here show only minor differences in cell number and viability, adenosine triphosphate levels, and measured respiratory chain activity compared with freshly harvested cells. Only 8-24 mL of human blood is needed for the described preparations, making it possible to collect samples during clinical studies multicentrally and determine their bioenergetics on site.

Combination of Secondary Plant Metabolites and Micronutrients Improves Mitochondrial Function in a Cell Model of Early Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by excessive formation of beta-amyloid peptides (Aß), mitochondrial dysfunction, enhanced production of reactive oxygen species (ROS), and altered glycolysis. Since the disease is currently not curable, preventive and supportive approaches are in the focus of science. Based on studies of promising single substances, the present study used a mixture (cocktail, SC) of compounds consisting of hesperetin (HstP), magnesium-orotate (MgOr), and folic acid (Fol), as well as the combination (KCC) of caffeine (Cof), kahweol (KW) and cafestol (CF). For all compounds, we showed positive results in SH-SY5Y-APP695 cells-a model of early AD. Thus, SH-SY5Y-APP695 cells were incubated with SC and the activity of the mitochondrial respiration chain complexes were measured, as well as levels of ATP, Aß, ROS, lactate and pyruvate. Incubation of SH-SY5Y-APP695 cells with SC significantly increased the endogenous respiration of mitochondria and ATP levels, while Aß1-40 levels were significantly decreased. Incubation with SC showed no significant effects on oxidative stress and glycolysis. In summary, this combination of compounds with proven effects on mitochondrial parameters has the potential to improve mitochondrial dysfunction in a cellular model of AD.

Geometric and Inertial Properties of the Pig Head and Brain in an Anatomical Coordinate System.

Porcine models in injury biomechanics research often involve measuring head or brain kinematics. Translation of data from porcine models to other biomechanical models requires geometric and inertial properties of the pig head and brain, and a translationally relevant anatomical coordinate system (ACS). In this study, the head and brain mass, center of mass (CoM), and mass moments of inertia (MoI) were characterized, and an ACS was proposed for the pre-adolescent domestic pig. Density-calibrated computed tomography scans were obtained for the heads of eleven Large White × Landrace pigs (18-48 kg) and were segmented. An ACS with a porcine-equivalent Frankfort plane was defined using externally palpable landmarks (right/left frontal process of the zygomatic bone and zygomatic process of the frontal bone). The head and brain constituted 7.80 ± 0.79% and 0.33 ± 0.08% of the body mass, respectively. The head and brain CoMs were primarily ventral and caudal to the ACS origin, respectively. The mean head and brain principal MoI (in the ACS with origin at respective CoM) ranged from 61.7 to 109.7 kg cm2, and 0.2 to 0.6 kg cm2, respectively. These data may aid the comparison of head and brain kinematics/kinetics data and the translation between porcine and human injury models.

Reframing research on evolutionary novelty and co-option: Character identity mechanisms versus deep homology.

A central topic in research at the intersection of development and evolution is the origin of novel traits. Despite progress on understanding how developmental mechanisms underlie patterns of diversity in the history of life, the problem of novelty continues to challenge researchers. Here we argue that research on evolutionary novelty and the closely associated phenomenon of co-option can be reframed fruitfully by: (1) specifying a conceptual model of mechanisms that underwrite character identity, (2) providing a richer and more empirically precise notion of co-option that goes beyond common appeals to "deep homology", and (3) attending to the nature of experimental interventions that can determine whether and how the co-option of identity mechanisms can help to explain novel character origins. This reframing has the potential to channel future investigation to make substantive progress on the problem of evolutionary novelty. To illustrate this potential, we apply our reframing to two case studies: treehopper helmets and beetle horns.

The hierarchical basis of serial homology and evolutionary novelty.

Given the pervasiveness of gene sharing in evolution and the extent of homology across the tree of life, why is everything not homologous with everything else? The continuity and overlapping genetic contributions to diverse traits across lineages seem to imply that no discrete determination of homology is possible. Although some argue that the widespread overlap in parts and processes should be acknowledged as "partial" homology, this threatens a broad base of presumed comparative morphological knowledge accepted by most biologists. Following a long scientific tradition, we advocate a strategy of "theoretical articulation" that introduces further distinctions to existing concepts to produce increased contrastive resolution among the labels used to represent biological phenomena. We pursue this strategy by drawing on successful patterns of reasoning from serial homology at the level of gene sequences to generate an enriched characterization of serial homology as a hierarchical, phylogenetic concept. Specifically, we propose that the concept of serial homology should be applied primarily to repeated but developmentally individualized body parts, such as cell types, differentiated body segments, or epidermal appendages. For these characters, a phylogenetic history can be reconstructed, similar to families of paralogous genes, endowing the notion of serial homology with a hierarchical, phylogenetic interpretation. On this basis, we propose a five-fold theoretical classification that permits a more fine-grained mapping of diverse trait-types. This facilitates answering the question of why everything is not homologous with everything else, as well as how novelty is possible given that any new character possesses evolutionary precursors. We illustrate the fecundity of our account by reference to debates over insect wing serial homologs and vertebrate paired appendages.

Cooption of polyalanine tract into a repressor domain in the mammalian transcription factor HoxA11.

An enduring problem in biology is explaining how novel functions of genes originated and how those functions diverge between species. Despite detailed studies on the functional evolution of a few proteins, the molecular mechanisms by which protein functions have evolved are almost entirely unknown. Here, we show that a polyalanine tract in the homeodomain transcription factor HoxA11 arose in the stem-lineage of mammals and functions as an autonomous repressor module by physically interacting with the PAH domains of SIN3 proteins. These results suggest that long polyalanine tracts, which are common in transcription factors and often associated with disease, may tend to function as repressor domains and can contribute to the diversification of transcription factor functions despite the deleterious consequences of polyalanine tract expansion.

Caenorhabditis elegans as a Model for the Effects of Phytochemicals on Mitochondria and Aging.

The study of aging is an important topic in contemporary research. Considering the demographic changes and the resulting shifts towards an older population, it is of great interest to preserve youthful physiology in old age. For this endeavor, it is necessary to choose an appropriate model. One such model is the nematode Caenorhabditis elegans (C. elegans), which has a long tradition in aging research. In this review article, we explore the advantages of using the nematode model in aging research, focusing on bioenergetics and the study of secondary plant metabolites that have interesting implications during this process. In the first section, we review the situation of aging research today. Conventional theories and hypotheses about the ongoing aging process will be presented and briefly explained. The second section focuses on the nematode C. elegans and its utility in aging and nutrition research. Two useful genome editing methods for monitoring genetic interactions (RNAi and CRISPR/Cas9) are presented. Due to the mitochondria's influence on aging, we also introduce the possibility of observing bioenergetics and respiratory phenomena in C. elegans. We then report on mitochondrial conservation between vertebrates and invertebrates. Here, we explain why the nematode is a suitable model for the study of mitochondrial aging. In the fourth section, we focus on phytochemicals and their applications in contemporary nutritional science, with an emphasis on aging research. As an emerging field of science, we conclude this review in the fifth section with several studies focusing on mitochondrial research and the effects of phytochemicals such as polyphenols. In summary, the nematode C. elegans is a suitable model for aging research that incorporates the mitochondrial theory of aging. Its living conditions in the laboratory are optimal for feeding studies, thus enabling bioenergetics to be observed during the aging process.

The value of broad taxonomic comparisons in evolutionary medicine: Disease is not a trait but a state of a trait!

In this short paper, we argue that there is a fundamental connection between the medical sciences and evolutionary biology as both are sciences of biological variation. Medicine studies pathological variation among humans (and domestic animals in veterinary medicine) and evolutionary biology studies variation within and among species in general. A key principle of evolutionary biology is that genetic differences among species have arisen first from mutations originating within populations. This implies a mechanistic continuity between variation among individuals within a species and variation between species. This fact motivates research that seeks to leverage comparisons among species to unravel the genetic basis of human disease vulnerabilities. This view also implies that genetically caused diseases can be understood as extreme states of an underlying trait, that is, an axis of variation, rather than distinct traits, as often assumed in GWAS studies. We illustrate these points with a number of examples as diverse as anatomical birth defects, cranio-facial variation, preeclampsia and vulnerability to metastatic cancer.

Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy.

CD44 is an extracellular matrix receptor implicated in cancer progression. CD44 increases the invasibility of skin (SF) and endometrial stromal fibroblasts (ESF) by cancer and trophoblast cells. We reasoned that the evolution of CD44 expression can affect both, the fetal-maternal interaction through CD44 in ESF as well as vulnerability to malignant cancer through expression in SF. We studied the evolution of CD44 expression in mammalian SF and ESF and demonstrate that in the human lineage evolved higher CD44 expression. Isoform expression in cattle and human is very similar suggesting that differences in invasibility are not due to the nature of expressed isoforms. We then asked whether the concerted gene expression increase in both cell types is due to shared regulatory mechanisms or due to cell type-specific factors. Reporter gene experiments with cells and cis-regulatory elements from human and cattle show that the difference of CD44 expression is due to cis effects as well as cell type-specific trans effects. These results suggest that the concerted expression increase is likely due to selection acting on both cell types because the evolutionary change in cell type-specific factors requires selection on cell type-specific functions. This scenario implies that the malignancy enhancing effects of elevated CD44 expression in humans likely evolved as a side-effect of positive selection on a yet unidentified other function of CD44. A possible candidate is the anti-fibrotic effect of CD44 but there are no reliable data showing that humans and primates are less fibrotic than other mammals.

Contaminant film thickness affects walkway friction measurements.

Walkway tribometers are used to measure available friction for evaluating walkway safety and pedestrian slip risk. Numerous variables can affect tribometer measurements, including the type and distribution of contaminants on the surface. Here, we quantified the effect of application method on contaminant film thickness, and the effect of film thickness on tribometer measurements on the four reference walkway surfaces used in ASTM F2508-16e. Distilled water, 0.05% sodium lauryl sulfate (SLS) solution, and 0.04% Triton X-100 solution were poured, squirted, and sprayed onto the surfaces to quantify their naturally occurring film thicknesses. These application methods had a significant effect on the resulting film thickness (p < 0.038), with the pour method consistently generating the thickest films and the spray method generating the thinnest films. We then quantified the effect of film thickness for the three contaminants (thickness range 0.3-3.3 mm) on the friction measurements of three common tribometers (Mark IIIB, English XL, and BOT 3000E) on each reference surface. A separate ANOVA was used for each of the 3 × 4 × 3 = 36 combinations of tribometer, surface, and contaminant. Friction measured with the Mark IIIB decreased with increasing film thickness on one surface across all three contaminants and on a second surface with the SLS contaminant. Friction measured with the BOT 3000E was sensitive to film thickness on two surfaces with water and one surface with Triton. The XL was unaffected by contaminant film thickness. Overall, despite significant differences in film thickness with contaminant application method, friction measurements were either insensitive to film thickness or varied only a small amount in all cases except for the Mark IIIB on the roughest surface. Film thickness did not alter the relative slip resistance of the four ASTM F2508 reference surfaces.