Decoding the control of food intake:Insights from the habenula and hypothalamus

This thesis focused on the habenula and hypothalamus, two brain regions important for reward in general and food intake specifically, and their role in regulating (palatable) food intake. We first described a free-choice high-fat high-sugar diet (fcHFHSD) commonly used in our laboratory as a tool to gain mechanistic insights into the relevant brain circuits in the development of obesity. Next, we studied two populations of lateral hypothalamic (LH) neurons, the GABAergic and glutamatergic neurons, and their responses to sucrose drinking and how this was affected by the consumption of a fcHFHSD. Next, we focussed on the (lateral) habenula (LHb) and described that blocking all glutamatergic input to the LHb did not acutely affect palatable feeding, but had a more slow, modulatory effect. This could be driven by specific inputs to the LHb, of which we reported one projection from the central amygdala (CeA) dopamine receptor 1 (Drd1) expressing neurons. When chemogenetically manipulated, this specific CeADrd1+ connection did alter feeding behavior in a satiety state-dependent manner. Finally, to add translational knowledge, we used functional magnetic resonance imaging (fMRI) to study the resting state functional connectivity (rsFC) of the habenula in humans. We reported an interaction effect between BMI and hemoglobin A1c (HbA1c) for the habenula-ventral tegmental area (VTA) connection’s rsFC, suggesting an additional role for the habenula in glucose regulation. In conclusion, in this thesis, we described experiments that contributed to our knowledge of the habenula and hypothalamus and their control over food intake in the context of obesity development

Comparing observed and modelled growth of larval herring (Clupea harengus): Testing individual-based model parameterisations

Experiments that directly test larval fish individual-based model (IBM) growth predictions are uncommon since it is difficult to simultaneously measure all relevant metabolic and behavioural attributes. We compared observed and modelled somatic growth of larval herring (Clupea harengus) in short-term (50 degree-day) laboratory trials conducted at 7 and 13°C in which larvae were either unfed or fed ad libitum on different prey sizes (~100 to 550 μm copepods, Acartia tonsa). The larval specific growth rate (SGR, % DW d-1) was generally overestimated by the model, especially for larvae foraging on large prey items. Model parameterisations were adjusted to explore the effect of 1) temporal variability in foraging of individuals, and 2) reduced assimilation efficiency due to rapid gut evacuation at high feeding rates. With these adjustments, the model described larval growth well across temperatures, prey sizes, and larval sizes. Although the experiments performed verified the growth model, variability in growth and foraging behaviour among larvae shows that it is necessary to measure both the physiology and feeding behaviour of the same individual. This is a challenge for experimentalists but will ultimately yield the most valuable data to adequately model environmental impacts on the survival and growth of marine fish early life stages. Comparación entre crecimiento observado y predicho de larvas de arenque (Clupea harengus): analizando parametrizaciones de modelos basados en individuos. – Los experimentos que analizan directamente las predicciones de crecimiento generadas por modelos basados en individuos (IBM) son poco comunes puesto que resulta difícil medir simultáneamente todos los atributos metabólicos y conductuales. En este estudio, comparamos el crecimiento somático observado y el estimado a partir de modelos de larvas de arenque (Clupea harengus) en experimentos de laboratorio a corto plazo (50 grados-día) a 7 y 13°en los que las larvas fueron mantenidas en condiciones de ayuno o recibieron alimentación ad libitum con diferentes tamaños de presa (copépodos, Acartia tonsa, de aproximadamente 100 a 500 μm). Las estimas de tasa específica de crecimiento (SGR, % de peso seco por día) fueron, en general, sobreestimadas por el modelo, especialmente para larvas que se alimentaron con presas grandes. estimas del modelo se ajustaron a dos escenarios para explorar el efecto de 1) variabilidad temporal en la alimentación de las larvas, y 2) disminución en la eficiencia de asimilación debida una rápida evacuación del tubo digestivo a tasas de alimentación altas. Con estos ajustes, el modelo describió bien el crecimiento larvario para temperaturas, tamaños de presa y edades de las larvas, indicando que las parametrizaciones metabólicas son robustas. Aunque los experimentos llevados a cabo con grupos de larvas verificaron los modelos de crecimiento, la variabilidad en el crecimiento y conducta de alimentación entre larvas sometidas a las mismas condiciones ambientales ponen de relieve la necesidad de que las medidas fisiológicas y de conducta vayan emparejadas y sean tomadas a nivel individual. Esto representa un reto para los experimentalistas, pero a largo plazo generará datos valiosos para los modeladores encargados de simular efectos ambientales sobre las tasas vitales de estadíos tempranos de desarrollo de peces marinos

Modeling printed circuit board curvature in relation to manufacturing process steps

This paper presents an analytical method to predict deformations of Printed Circuit Boards (PCBs) in relation to their manufacturing process steps. Classical Lamination Theory (CLT) is used as a basis. The model tracks internal stresses and includes the results of subsequent production steps, such as bonding, multilayer press cycles and patterning processes. The aim of this research is to develop a model that can be applied to predict laminate deformations in the production of complex PCBs. Initial experimental results of simplified test specimens show that the modeling approach is valid and capable of accurately predicting laminate deformations for standard bi-layer bonding and multiple press cycles. In the future, the evolved model can be used to analyze PCB manufacturing processes and optimize PCB desig

Hypoxia in the Holocene Baltic Sea : Comparing modern versus past intervals using sedimentary trace metals

Anthropogenic nutrient input has caused a rapid expansion of bottom water hypoxia in the Baltic Sea over the past century. Two earlier intervals of widespread hypoxia, coinciding with the Holocene Thermal Maximum (HTMHI; 8-4 ka before present; BP) and the Medieval Climate Anomaly (MCA(HI); similar to 1200-750 years BP), have been identified from Baltic Sea sediments. Here we present sediment records from two sites in the Baltic Sea, and compare the trace metal (As, Ba, Cd, Cu, Mo, Ni, Pb, Re, Sb, Tl, U, V, Zn) enrichments during all three hypoxic intervals. Distinct differences are observed between the intervals and the various elements, highlighting the much stronger perturbation of trace metal cycles during the modern hypoxic interval. Both Mo and U show a strong correlation with C-org and very high absolute concentrations, indicative of frequently euxinic bottom waters during hypoxic intervals. During the modern hypoxic interval (Modern(HI)) comparatively less Mo is sequestered relative to C-org than in earlier intervals. This suggests partial drawdown of the water column Mo inventory in the modern water column due to persistent euxinia and only partial replenishment of Mo through North Sea inflows. Molybdenum contents in modern sediments are likely also affected by the recent slowdown in input of Mo in association with deposition of Fe and Mn oxides. Strong enrichments of U in recent sediments confirm that the Modern(HI) is more intense than past intervals. These results suggest that U is a more reliable indicator for the intensity of bottom water deoxygenation in the Baltic Sea than Mo. Sedimentary Re enrichment commences under mildly reducing conditions, but this element is not further enriched under more reducing conditions. Enrichments of V are relatively minor for the MCA(HI) and Modern(HI), possibly due to strong reservoir effects on V in the water column, indicating that V is unreliable as an indicator for the intensity of bottom water hypoxia in this setting. Furthermore, Ba profiles are strongly influenced by post-depositional remobilization throughout the Holocene. The strong relationship between C-org and Ni, Tl and particularly Cu suggests that these trace metals can be used to reconstruct the C-org flux into the sediments. Profiles of As, Sb and Cd and especially Pb and Zn are strongly influenced by anthropogenic pollution.Peer reviewe

Recovery from multi‐millennial natural coastal hypoxia in the Stockholm Archipelago, Baltic Sea, terminated by modern human activity

Enhanced nutrient input and warming have led to the development of low oxygen (hypoxia) in coastal waters globally. For many coastal areas, insight into redox conditions prior to human impact is lacking. Here, we reconstructed bottom water redox conditions and sea surface temperatures (SSTs) for the coastal Stockholm Archipelago over the past 3000 yr. Elevated sedimentary concentrations of molybdenum indicate (seasonal) hypoxia between 1000b.c.e.and 1500c.e. Biomarker-based (TEX86) SST reconstructions indicate that the recovery from hypoxia after 1500c.e.coincided with a period of significant cooling (similar to 2 degrees C), while human activity in the study area, deduced from trends in sedimentary lead and existing paleobotanical and archeological records, had significantly increased. A strong increase in sedimentary lead and zinc, related to more intense human activity in the 18(th)and 19(th)century, and the onset of modern warming precede the return of hypoxia in the Stockholm Archipelago. We conclude that climatic cooling played an important role in the recovery from natural hypoxia after 1500c.e., but that eutrophication and warming, related to modern human activity, led to the return of hypoxia in the 20(th)century. Our findings imply that ongoing global warming may exacerbate hypoxia in the coastal zone of the Baltic Sea

Efficacy of natural antimicrobials in toothpaste formulations against oral biofilms in vitro

AbstractObjectivesTo evaluate the antimicrobial efficacies of two toothpaste formulations containing natural antimicrobials (herbal extracts and chitosan) against oral biofilms of different composition and maturational status.MethodsBacteria from a buffer suspension or fresh saliva were adhered for 2h to a salivary conditioning film and subsequently grown for 16h. Dual-species biofilms were prepared from Actinomyces naeslundii T14V-J1 and Streptococcus oralis J22, whilst multi-species biofilms were grown from freshly collected human saliva. Biofilms were exposed to 25wt% toothpaste supernatants. A chlorhexidine-containing mouthrinse and a buffer were used as positive- and negative-controls, respectively. Antibacterial efficacy was concluded from acute killing, bacterial removal, prevention of bacterial re-deposition and continued killing during re-deposition.ResultsThe herbal- and chitosan-based supernatants showed immediate killing of oral biofilm bacteria, comparable with chlorhexidine. Moreover, exposure of a biofilm to these supernatants or chlorhexidine, yielded ongoing killing of biofilm bacteria after exposure during re-deposition of bacteria to a matured 16h biofilm, but not to a much thinner initial biofilm formed by 2h adhesion only. This suggests that thicker, more matured biofilms can absorb and release oral antimicrobials.ConclusionsSupernatants based on herbal- and chitosan-based toothpastes have comparable immediate and ongoing antibacterial efficacies as chlorhexidine. Natural antimicrobials and chlorhexidine absorb in oral biofilms which contributes to their substantive action

Iron-Phosphorus Feedbacks Drive Multidecadal Oscillations in Baltic Sea Hypoxia

Hypoxia has occurred intermittently in the Baltic Sea since the establishment of brackish-water conditions at similar to 8,000 years B.P., principally as recurrent hypoxic events during the Holocene Thermal Maximum (HTM) and the Medieval Climate Anomaly (MCA). Sedimentary phosphorus release has been implicated as a key driver of these events, but previous paleoenvironmental reconstructions have lacked the sampling resolution to investigate feedbacks in past iron-phosphorus cycling on short timescales. Here we employ Laser Ablation (LA)-ICP-MS scanning of sediment cores to generate ultra-high resolution geochemical records of past hypoxic events. We show that in-phase multidecadal oscillations in hypoxia intensity and iron-phosphorus cycling occurred throughout these events. Using a box model, we demonstrate that such oscillations were likely driven by instabilities in the dynamics of iron-phosphorus cycling under preindustrial phosphorus loads, and modulated by external climate forcing. Oscillatory behavior could complicate the recovery from hypoxia during future trajectories of external loading reductions.Peer reviewe

Altered cholinergic innervation in De Novo Parkinson's disease with and without cognitive impairment

BACKGROUND: Altered cholinergic innervation plays a putative role in cognitive impairment in Parkinson's disease (PD) at least in advanced stages. Identification of the relationship between cognitive impairment and cholinergic innervation early in the disease will provide better insight into disease prognosis and possible early intervention. OBJECTIVE: The aim was to assess regional cholinergic innervation status in de novo patients with PD, with and without cognitive impairment. METHODS: Fifty-seven newly diagnosed, treatment-naive, PD patients (32 men, mean age 64.6 ± 8.2 years) and 10 healthy controls (5 men, mean age 54.6 ± 6.0 years) were included. All participants underwent cholinergic [18 F]fluoroethoxybenzovesamicol positron emission tomography and detailed neuropsychological assessment. PD patients were classified as either cognitively normal (PD-NC) or mild cognitive impairment (PD-MCI). Whole brain voxel-based group comparisons were performed. RESULTS: Results show bidirectional cholinergic innervation changes in PD. Both PD-NC and PD-MCI groups showed significant cortical cholinergic denervation compared to controls (P < 0.05, false discovery rate corrected), primarily in the posterior cortical regions. Higher-than-normal binding was most prominent in PD-NC in both cortical and subcortical regions, including the cerebellum, cingulate cortex, putamen, gyrus rectus, hippocampus, and amygdala. CONCLUSION: Altered cholinergic innervation is already present in de novo patients with PD. Posterior cortical cholinergic losses were present in all patients independent of cognitive status. Higher-than-normal binding in cerebellar, frontal, and subcortical regions in cognitively intact patients may reflect compensatory cholinergic upregulation in early-stage PD. Limited or failing cholinergic upregulation may play an important role in early, clinically evident cognitive impairment in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Coupled Dynamics of Iron and Phosphorus in Sediments of an Oligotrophic Coastal Basin and the Impact of Anaerobic Oxidation of Methane

Studies of phosphorus (P) dynamics in surface sediments of lakes and coastal seas typically emphasize the role of coupled iron (Fe), sulfur (S) and P cycling for sediment P burial and release. Here, we show that anaerobic oxidation of methane (AOM) also may impact sediment P cycling in such systems. Using porewater and sediment profiles for sites in an oligotrophic coastal basin (Bothnian Sea), we provide evidence for the formation of Fe-bound P (possibly vivianite; Fe3(PO4)2.8H2O) below the zone of AOM with sulfate. Here, dissolved Fe2+ released from oxides is no longer scavenged by sulfide and high concentrations of both dissolved Fe2+ (>1 mM) and PO4 in the porewater allow supersaturation with respect to vivianite to be reached. Besides formation of Fe(II)-P, preservation of Fe-oxide bound P likely also contributes to permanent burial of P in Bothnian Sea sediments. Preliminary budget calculations suggest that the burial of Fe-bound P allows these sediments to act as a major sink for P from the adjacent eutrophic Baltic Proper

Anthropogenic and climatic impacts on a coastal environment in the Baltic Sea over the last 1000 years

Coastal environments have experienced large ecological changes as a result of human activities over the last 100-200 years. To understand the severity and potential consequences of such changes, paleoenvironmental records provide important contextual information. The Baltic Sea coastal zone is naturally a vulnerable system and subject to significant human-induced impacts. To put the recent environmental degradation in the Baltic coastal zone into a long-term perspective, and to assess the natural and anthropogenic drivers of environmental change, we present sedimentary records covering the last 1000 years obtained from a coastal inlet (Gasfjarden) and a nearby lake (Lake Storsjon) in Sweden. We investigate the links between a pollen-based land cover reconstruction from Lake Storsjon and paleoenvironmental variables from Gasfjarden itself, including diatom assemblages, organic carbon (C) and nitrogen (N) contents, stable C and N isotopic ratios, and biogenic silica contents. The Lake Storsjon record shows that regional land use was characterized by small-scale agricultural activity between 900 and 1400 CE, which slightly intensified between 1400 and 1800 CE. Substantial expansion of cropland was observed between 1800 and 1950 CE, before afforestation between 1950 and 2010 CE. From the Gasfjarden record, prior to 1800 CE, relatively minor changes in the diatom and geochemical proxies were found. The onset of cultural eutrophication in Gasfjarden can be traced to the 1800s and intensified land use is identified as the main driver. Anthropogenic activities in the 20th century have caused unprecedented ecosystem changes in the coastal inlet, as reflected in the diatom composition and geochemical proxies. (c) 2018 Elsevier Ltd. All rights reserved.Peer reviewe