Detrimental Interactions Research Articles

Laboratory Guidelines for Animal Care.

Animal research is a controversial subject because of the ethical and moral implications of using unwilling research subjects in potentially painful or distressful procedures usually ending in euthanasia. As such, it must be conducted in a compassionate and responsible manner geared toward maximizing the animals' quality of life prior to and during experimentation. Because of its contentious nature, the conduct of animal research is highly regulated at the federal, state, city, and institutional levels. It is essential that researchers acquire a thorough knowledge of the procedures to be conducted as well as a working knowledge of the regulations. This will maximize humane care of research animals and prevent potentially negative or detrimental interactions with groups opposed to using animals in biomedical research. Perhaps the best way to attain these goals is to avoid inadvertent instances of noncompliance with their research protocol or applicable regulations. Regulatory noncompliance can also have serious negative consequences on investigators' research careers ranging from temporary suspension of their protocols to loss of funding and revocation of principal investigator status and associated privileges. To minimize such adverse outcomes, it is advised that researchers build positive and collaborative relationships with key institutional players such as the veterinary staff, the Institutional Animal Care and Use Committee (IACUC), and top administrators. Guidance is provided regarding the appropriate handling of regulatory noncompliance.

Membrane domain modulation of Aβ1-42 oligomer interactions with supported lipid bilayers: an atomic force microscopy investigation.

Alzheimer's disease is a devastating pathology affecting an increasing number of individuals following the general rise in life expectancy. Amyloid peptide Aβ1-42 has been identified as one of the main culprits of the disease. The peptide has been shown to have major effects on lipid membranes, including membrane fragmentation. The membrane composition has been identified as a factor that plays a pivotal role in regulating peptide/membrane interactions and several results suggest that lipid domains, or rafts, can promote peptide-induced membrane damage. In this work, we examined the effects of lipid segregation on the membrane-perturbing ability of Aβ1-42 and an oligomeric mutant (G37C), a peptide that shares common features with the suspected toxic intermediates involved in the neurodegeneration process. Atomic force microscopy (AFM) was used to determine the impact of these peptides on the supported lipid bilayers of various compositions. In 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol (DOPC/DPPC/cholesterol) and DOPC/sphingomyelin/cholesterol ternary mixtures, two systems exhibiting liquid-liquid phase separations, it was shown that Aβ1-42 and G37C exclusively aggregated on liquid-disordered-phase domains, creating large deposits and even causing membrane fragmentation for the latter composition. Cholesterol and ganglioside GM1, the two most documented lipids in the context of Alzheimer's disease, are also considered to play a crucial role in promoting detrimental interactions with amyloid peptides. We show that, in model 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes, the presence of either cholesterol or GM1 in a proportion of 10 mol%, a content supposed to lead to domain formation, favoured the association of both Aβ1-42 and G37C, leading to a harmful membrane fragmentation. The AFM results established that the presence of domains favoured membrane perturbations induced by the amyloid peptides. It is proposed that lipid packing defects at the domain interface could act as adsorption and nucleation sites for the amyloid peptides. The more extensive bilayer perturbations induced by G37C compared to Aβ1-42 supported this hypothesis, indicating that oligomers that cannot mature to the fibril state can present considerable toxicity.

Genomic Balance and Speciation.

The role of genomic balance in accumulating species hybrid incompatibilities is discussed. Aneuploidy has been shown to produce more global modulations than polyploidy with the responsible genes being transcription factors and signaling components involved in molecular complexes, illustrating a stoichiometric component to gene expression. Genomic imbalance is usually detrimental to the organism and in many cases results in lethality. Here, it is proposed that once gene flow is prevented between or within populations by various speciation initiating processes, the stoichiometric relationship of members of macromolecular complexes can change via compensatory drift with the eventual result of newly established functional balances. However, when these new relationships are brought together in interspecific hybrids, detrimental consequences will occur. We suggest that these detrimental interactions contribute to hybrid incompatibilities.

Fatigue in survivors of malignant melanoma and its determinants: a register-based cohort study.

Fatigue has found increasing attention as a debilitating and lasting condition of cancer patients. However, it has remained unclear to what degree long-term survivors of malignant melanoma suffer from fatigue. Therefore, this study aimed to determine fatigue and its link with quality of life, aftercare behavior, and mental and physical symptoms among melanoma survivors. A register-based sample of 684 long-term survivors an average of 8.4 (SD = 1.72; range 5.67-12.17) years after diagnosis was compared to 2049 participants from a representative survey by the Multidimensional Fatigue Inventory. In a hierarchical linear regression, statistical predictors for fatigue were ascertained. Overall fatigue was not increased in melanoma survivors except for younger melanoma survivors under 40years. As in the general population, fatigue increased with age, and it was higher in women compared to men. Fatigue was associated with decreased quality of life, reduced functioning, and increased physical and mental symptoms. Substantial predictors (30% explained variance) were higher age, additional chronic illness, self-blame, detrimental interactions and lack of social support, and also fear of recurrence. There was neither an effect of medical parameters (clinical stage, time since diagnosis) nor of participation in follow-up care. Fatigue needs to be taken seriously in the aftercare of melanoma survivors as it is associated with multiple functional and quality of life impairments and heightened distress. Reduction of fatigue in melanoma patients should address younger survivors (under 40years) and older survivors (over 60years) with additional chronic illness and focus on illness coping and social support.

Universality of Poisson-driven plasma fluctuations in the Alcator C-Mod scrape-off layer

Large-amplitude, intermittent fluctuations are ubiquitous in the boundary region of magnetically confined plasmas and lead to detrimental plasma-wall interactions in next-generation, high duty cycle fusion power experiments. Using gas puff imaging data time series from the scrape-off layer in the Alcator C-Mod device, it is here demonstrated that the large-amplitude fluctuations can be described as a super-position of pulses with a fixed shape and a constant duration. By applying a new deconvolution algorithm on the data time series with a two-sided exponential pulse function, the arrival times and amplitudes of the pulses can be estimated, and the measurement time series can be reconstructed with high accuracy. The pulse amplitudes are shown to follow an exponential distribution. The waiting times between pulses are uncorrelated, their distribution has an exponential tail, and the number of arrivals is a linear function of time. This demonstrates that pulse arrivals follow a homogeneous Poisson process. Identical statistical properties apply to both ohmic and high confinement mode plasmas, clearly demonstrating the universality of the fluctuation statistics in the boundary region of Alcator C-Mod.

Free-Living Nematodes Together With Associated Microbes Play an Essential Role in Apple Replant Disease.

Apple replant disease (ARD) is a severe problem in apple production worldwide. It is caused by a complex of soil biota, leading to small discolorated roots, as well as increased biosynthesis of phytoalexins, total phenolic compounds and antioxidants. We sampled soil from randomized field plots with either apple trees affected by ARD, which were five times replanted every second year, or with healthy trees growing in plots, which had a grass cover during this period. We investigated the contribution of nematodes to ARD by dissecting the soil biota from plots infested with ARD and non-infested control plots into a nematode and a microbe fraction. Nematode communities significantly differed between ARD and control soil as revealed by high-throughput sequencing of 18S rRNA genes. Plant-parasitic nematodes were too low in abundance to explain root damage, and did not significantly differ between ARD and control soil. Their separate and synergistic effect on ARD symptoms of susceptible M26 apple rootstocks was analyzed 4 and 8 weeks after inoculation in three greenhouse experiments. Inoculants were either nematodes from ARD plots (NARD), NARD plus microbes from ARD plots (MARD), NARD plus microbes from control plots (MCon), nematodes from control plots NCon plus MARD, NCon plus MCon, MARD, or MCon, or non-inoculated control. In all three experiments, the combination NARD plus MARD had the strongest adverse effect on the plants, with respect to growth parameters of shoots and roots, total phenolic compounds and phytoalexins in roots, and antioxidants in leaves. NARD also induced ARD but less than NARD plus MARD. NARD plus MCon had delayed effects on the plants compared to NARD plus MARD, suggesting that detrimental nematode-microbe interactions built up with time. Effects of MARD or NCon plus MARD were minor or not distinguishable from those of MCon or non-inoculated control. Overall, the source of the inoculated nematodes -ARD or control soil- and the interaction between ARD nematodes and microbes were highly significant factors determining ARD. In conclusion, exploring the associations of nematodes and microbes in ARD soils will give the chance to unravel the etiology of ARD.

Homogeneous acylation of Cellulose diacetate: Towards bioplastics with tuneable thermal and water transport properties

In this study, we report a simple, non-degrading and efficient homogeneous acylation of cellulose diacetate (CDA) by using a large panel of commercially available acylating aliphatic moieties, differing in their structure (fatty, ramified, bulky, cycloaliphatic, aromatic, more or less spaced from the cellulose backbone), in view of generating a library of well-defined cellulose mixed esters with enhanced thermoplasticity. As reflected by a lowering of the glass temperature (Tg), the covalent grafting confers an improved mobility to the cellulose chains, by disrupting the initial H-bonds. In particular, it appears that the gain in free volume is tailored by the substituent structure and that acylating reagents consisting in a terminal bulky moieties spaced from CDA chains by a linear chain efficiently separate macromolecular chains without generating detrimental stiffening interactions (low Tg around 125 °C). Moreover, free-standing films easily prepared by solvent casting exhibit relevant water transport properties, which are closely dictated and tuned by the water solubility of the cellulose mixed ester.

K-Selection as Microbial Community Management Strategy: A Method for Improved Viability of Larvae in Aquaculture.

Aquaculture has the potential to become a major food supplier in a world with an increasing human population, and increased consumption of fish will likely have positive health implications. For marine aquaculture, the production of high quality juveniles is a bottleneck. Survival until the juvenile stage is typically as low as 10–15% for many species, which indicates suboptimal rearing conditions. Substantial evidence indicates that the poor performance and viability of larvae is largely due to detrimental larvae-microbiota interactions. This emphasises the need for microbial management strategies in the cultivation of marine fish larvae. Disinfection and probiotics are the most studied microbial management methods so far. However, most studies on these methods overlooked the role of mutualistic relationships between microbes and hosts, and have not proposed or examined methods steering toward such relationships. Based on ecological theory and a number of experiments, we find support for the hypothesis that current practise in aquaculture generally selects for r-strategic, opportunistic microbes, which results in detrimental host–microbiota interactions. Thus, the challenge is to develop technology and methods for microbial management at the ecosystem level that creates a K-selected microbial community, and by this mean select against r-strategic opportunists. Here we summarise experiments done during 25 years and with marine larvae of five different species showing that: (1) K-selection strategies result in different water microbiota with less opportunists, (2) this influences the microbiota of the fish larvae, and (3) the larvae cultivated in water inhabited by a K-selected microbiota perform better. Improved performance of larvae includes improved appetite, earlier onset of and faster growth, increased survival, and increased robustness to stress. K-selection as a method for management of the microbial community is a robust approach that allows steering of host–microbiota interactions in larviculture toward mutualism. It could also be applicable for young stages of other domesticated animals. Our review illustrates that a change from a “beat-them” to a “join-them” strategy for microbial management in larval rearing can lead to a more sustainable aquaculture industry.

Effects of changes in soil moisture and precipitation patterns on plant-mediated biotic interactions in terrestrial ecosystems

Due to climate change, the amount, frequency, and intensity of precipitation worldwide are changing. There is increasing evidence that hydrological change severely affects species interactions and that these effects might overrule direct autecological responses, although this is currently understudied. Here, I synthesize published data on 405 interactions to show how changes in soil moisture affect the frequency or strength of plant-mediated biotic interactions. Despite substantial variation among published responses, general patterns have emerged. A recurrent finding in the synthesized studies is that dryness impedes beneficial interactions between plants and other organisms (decreased mycorrhization and infection with other symbiotic endophytes, less pollinator visits, less active decomposers) and increases detrimental interactions (increased performance of sucking insects, pathogen infection and competition between functionally similar plants). For increased wetness, which is far less studied, stress intensity seems to matter: Slightly increased precipitation often benefits plants and thereby associated interaction partners (increased mycorrhization and infection with symbiotic endophytes, increased herbivore performance), while extreme waterlogging or flooding impedes many interactions (decreased decomposer activity and mycorrhization). Legacy effects of changed soil moisture on plant community composition can amplify or reverse short-term effects on interactions. Although some concepts acknowledge the role of stress intensity (mild versus severe) and stress type (permanent versus pulsed) empirical research testing-related hypotheses is largely lacking, as is research on the role of soil moisture legacies for interactions.

Strain and Rotational Mechanics in Children With Single Left Ventricles After Fontan

Left ventricular (LV) mechanics in patients with different single morphologic LV subtypes, including tricuspid atresia, double-inlet left ventricle, and pulmonary atresia with intact ventricular septum, remain poorly studied. Given that histologic studies indicate differences in LV myocardial fiber orientation, we hypothesized that this may result in altered LV mechanics. The aim of this study was to evaluate the influence of LV morphology on LV mechanics. Fifty-two children with single left ventricles after Fontan operation and age-matched control subjects were prospectively enrolled. Using two-dimensional speckle-tracking echocardiography, longitudinal strain was measured in the four-, three-, and two-chamber long-axis planes, and circumferential strain was measured at the basal, mid, and apical short-axis planes. Apical and basal rotation were measured, and twist and torsion were calculated. We compared strain and rotational mechanics in cases versus control subjects and among LV subtypes. Compared with control subjects, subjects with single left ventricles had similar LV end-diastolic dimensions but significantly decreased ejection fractions. The single left ventricle cohort had normal global longitudinal strain (P=.20) but lower basal mean circumferential strain (P<.0001). Single left ventricle subjects had higher apical rotation (P=.0001) but decreased basal rotation (P=.0007); there was no difference in twist but increased torsion (P=.001). LV subtypes had different four-chamber (P=.01), two-chamber (P=.006), and global longitudinal strain (P=.01), lowest in the pulmonary atresia with intact ventricular septum subtype. Longitudinal LV strain was preserved in children with single left ventricles after Fontan. A pattern of reduced basal circumferential strain and rotation with an increase in apical rotation and torsion in the single left ventricle cohort may be related to differences in myofiber orientation, increased fibrosis, and the impact of altered loading conditions throughout palliation. Decreased longitudinal strain in the pulmonary atresia with intact ventricular septum group may also reflect detrimental interventricular interactions.

Lysosome biogenesis in health and disease.

This review focuses on the pathways that regulate lysosome biogenesis and that are implicated in numerous degenerative storage diseases, including lysosomal storage disorders and late-onset neurodegenerative diseases. Lysosomal proteins are synthesized in the endoplasmic reticulum and trafficked to the endolysosomal system through the secretory route. Several receptors have been characterized that execute post-Golgi trafficking of lysosomal proteins. Some of them recognize their cargo proteins based on specific amino acid signatures, others based on a particular glycan modification that is exclusively found on lysosomal proteins. Nearly all receptors serving lysosome biogenesis are under the transcriptional control of transcription factor EB (TFEB), a master regulator of the lysosomal system. TFEB coordinates the expression of lysosomal hydrolases, lysosomal membrane proteins, and autophagy proteins in response to pathways sensing lysosomal stress and the nutritional conditions of the cell among other stimuli. TFEB is primed for activation in lysosomal storage disorders but surprisingly its function is impaired in some late-onset neurodegenerative storage diseases like Alzheimer's and Parkinson's, because of specific detrimental interactions that limit TFEB expression or activation. Thus, disrupted TFEB function presumably plays a role in the pathogenesis of these diseases. Multiple studies in animal models of degenerative storage diseases have shown that exogenous expression of TFEB and pharmacological activation of endogenous TFEB attenuate disease phenotypes. These results highlight TFEB-mediated enhancement of lysosomal biogenesis and function as a candidate strategy to counteract the progression of these diseases. This article is part of the Special Issue "Lysosomal Storage Disorders".

Life satisfaction in young adults with cancer and the role of sociodemographic, medical, and psychosocial factors: Results of a longitudinal study.

Being diagnosed with and treated for cancer often has a strong impact on the life satisfaction (LS) of adolescents and young adults (AYAs). The current study investigated LS in AYA patients with cancer and determined associated factors. Young patients (those aged 18-39 years at the time of diagnosis) with all malignant cancer sites and with a diagnosis made within the last 4 years were assessed. LS was measured at 2 measuring time points using the Questions on Life Satisfaction (FLZ-M). Differences in the FLZ-M and the 10 subdomains (friends/acquaintances, leisure activities/hobbies, health, income/financial security, work/profession, housing situation, family life, children/family planning, partnership, and sexuality) between the 2 time points were calculated. Multiple regression analyses were conducted to determine factors associated with LS. A total of 514 patients (386 of whom were women) with a mean age at diagnosis of 29.6 years participated at both measurements. LS increased significantly in 5 domains with a small effect (Hedges g, 0.17) noted over time. The subdomains with the lowest LS were financial and professional situation, family planning, and sexuality. Significant associations with LS were found at baseline for sociodemographic, medical, and psychosocial variables (explained variance [R2 ]baseline = 0.41). At follow-up, psychosocial factors (positive social support, not having detrimental interactions, and lower perceived adjustment to the disease) remained most important for higher LS controlled for LS at baseline. Neither sociodemographic (except partnership) nor medical factors played a role (R2follow-up = 0.54). Of all the variables examined, social support was found to be the most decisive factor associated with LS at both time points. With regard to LS, social support and adjustment to illness should be given more consideration in the medical care of AYA patients with cancer.

Pulsed Electron Decoupling and Strategies for Time Domain Dynamic Nuclear Polarization with Magic Angle Spinning.

Magic angle spinning (MAS) dynamic nuclear polarization (DNP) is widely used to increase nuclear magnetic resonance (NMR) signal intensity. Frequency-chirped microwaves yield superior control of electron spins and are expected to play a central role in the development of DNP MAS experiments. Time domain electron control with MAS has considerable promise to improve DNP performance at higher fields and temperatures. We have recently demonstrated that pulsed electron decoupling using frequency-chirped microwaves improves MAS DNP experiments by partially attenuating detrimental hyperfine interactions. The continued development of pulsed electron decoupling will enable a new suite of MAS DNP experiments that transfer polarization directly to observed spins. Time domain DNP transfers to nuclear spins in conjunction with pulsed electron decoupling is described as a viable avenue toward DNP-enhanced, high-resolution NMR spectroscopy over a range of temperatures from <6 to 320 K.

Managing the Microbial Community of Marine Fish Larvae: A Holistic Perspective for Larviculture.

The availability of high-quality juveniles is a bottleneck in the farming of many marine fish species. Detrimental larvae-microbe interactions are a main reason for poor viability and quality in larval rearing. In this review, we explore the microbial community of fish larvae from an ecological and eco-physiological perspective, with the aim to develop the knowledge basis for microbial management. The larvae are exposed to a huge number of microbes from external and internal sources in intensive aquaculture, but their relative importance depend on the rearing technology used (especially flow-through vs. recirculating systems) and the retention time of the water in the fish tanks. Generally, focus has been on microbes entering the system, but microbes from growth within the system is normally a substantial part of the microbes encountered by larvae. Culture independent methods have revealed an unexpected high richness of bacterial species associated with larvae, with 100–250 operational taxonomic units associated with one individual. The microbiota of larvae changes rapidly until metamorphosis, most likely due to changes in the selection pressure in the digestive tract caused by changes in host-microbe and microbe-microbe interactions. Even though the microbiota of larvae is distinctly different from the microbiota of the water and the live food, the microbiota of the water strongly affects the microbiota of the larvae. We are in the early phase of understanding larvae-microbe interactions in vivo, but some studies with other animals than fish emphasize that we so far have underestimated the complexity of these interactions. We present examples demonstrating the diversity of these interactions. A large variety of microbial management methods exist, focusing on non-selective reduction of microbes, selective enhancement of microbes, and on improvement of the resistance of larvae against microbes. However, relatively few methods have been studied extensively. We believe that there is a lot to gain by increasing the diversity of approaches for microbial management. As many microbial management methods are perturbations of the microbial community, we argue that ecological theory is needed to foresee and test for longer term consequences in microbe-microbe and microbe-larvae interactions. We finally make some recommendations for future research and development.

The “Polyploid Hop”: Shifting Challenges and Opportunities Over the Evolutionary Lifespan of Genome Duplications

The duplication of an entire genome is no small affair. Whole genome duplication (WGD) is a dramatic mutation with long-lasting effects, yet it occurs repeatedly in all eukaryotic kingdoms. Plants are particularly rich in documented WGDs, with recent and ancient polyploidization events in all major extant lineages. However, challenges immediately following WGD, such as the maintenance of stable chromosome segregation or detrimental ecological interactions with diploid progenitors, commonly do not permit establishment of nascent polyploids. Despite these immediate issues some lineages nevertheless persist and thrive. In fact, ecological modelling supports patterns of adaptive niche differentiation in polyploids, with young polyploids often invading new niches and leaving their diploid progenitors behind. In line with these observations of polyploid evolutionary success, recent work documents instant physiological consequences of WGD associated with increased dehydration stress tolerance in first-generation autotetraploids. Furthermore, population genetic theory predicts both short- and long-term benefits of polyploidy and new empirical data suggests that established polyploids may act as ‘sponges’ accumulating adaptive allelic diversity. In addition to their increased genetic variability, introgression with other tetraploid lineages, diploid progenitors, or even other species, further increases the available pool of genetic variants to polyploids. Despite this, the evolutionary advantages of polyploidy are still questioned, and the debate over the idea of polyploidy as an evolutionary dead-end carries on. Here we broadly synthesise the newest empirical data moving this debate forward. Altogether, evidence suggests that if early barriers are overcome, WGD can offer instantaneous fitness advantages opening the way to a transformed fitness landscape by sampling a higher diversity of alleles, including some already preadapted to their local environment. This occurs in the context of intragenomic, population genomic, and physiological modifications that can, on occasion, offer an evolutionary edge. Yet in the long run, early advantages can turn into long-term hindrances, and without ecological drivers such as novel ecological niche availability or agricultural propagation, a restabilization of the genome via diploidization will begin the cycle anew.

Intercameral Relations in a Bicameral Elected and Sortition Legislature

The idea of a hybrid bicameral system combining election and sortition is investigated. More precisely, the article imagines how an elected and a sortition chamber would interact, taking into account their public perception and their competing legitimacies. The article draws on a survey of a representative sample of the Belgian population and Belgian members of parliament assessing their views about sortition in political representation. Findings are combined with theoretical reflections on election’s and sortition’s respective sources of legitimacy. The possibility of conflicting legitimacies and mutually detrimental interactions leads to considerations of the effects of different possible distributions of power between the chambers as a crucial determinant of their interactions and perceived legitimacy.

Determinants of illness-specific social support and its relation to distress in long-term melanoma survivors

BackgroundSocial support is considered to be one of the most important resources for coping with cancer. However, social interactions may also be detrimental, e. g. disappointing or discouraging. The present study explored: 1. the extent of illness-specific positive aspects of social support and detrimental interactions in melanoma survivors, 2. their relationships to mental health characteristics (e. g. distress, quality of life, fatigue, coping processes, and dispositional optimism) and 3. Combinations of positive social support and detrimental interactions in relation to depression and anxiety.MethodsBased on the cancer registry of Rhineland-Palatinate, Germany, melanoma patients diagnosed at least 5 years before the survey were contacted by their physicians. N = 689 melanoma patients filled out the Illness-specific Social Support Scale ISSS (German version) and standardised instruments measuring potential psychosocial determinants of social support.ResultsUsing principal component analysis, the two factor structure of the ISSS could be reproduced with acceptable reliability; subscales were “Positive Support” (PS) and “Detrimental Interactions” (DI); Cronbach’s α = .95/.72. PS was rated higher than DI. Multivariable linear regressions identified different associations with psychosocial determinants. Survivors living in a partnership and those actively seeking out support had a higher probability of receiving PS, but not DI. PS and DI interacted regarding their association with distress: Survivors reporting high DI but low PS were the most depressed and anxious. High DI was partly buffered by PS. When DI was low, high or low PS made no difference regarding distress.ConclusionPsycho-oncologic interventions should take into account both positive and negative aspects of support in order to promote coping with the disease.

Programmed Self-Assembly of Highly Fluorescent Nanostructures Formed By Host-Included Porphyrins

The propensity for pi-rich aromatic chromophores such as porphyrins and phthalocyanines to aggregate in water is a critical issue that limits the full application of these photoactive molecules. In this talk, we will illustrate how defined self-assemblies and nanoarchitectures containing well-placed porphyrin moieties can be achieved in water using hierarchical self-assembly that focuses on inter- and intra-molecular host-guest chemistry and other assembly modalities such as programmable DNA self-assembly. Importantly, the individual porphyrin units in these architectures are precluded from detrimental aromatic stacking interactions (via host-guest assembly) and thus exhibit enhanced photophysical properties. We will commence by discussing the generation of multi-porphyrin containing wires, spheres, and thin films. We will then detail our recent work on photonic nanocylinders composed of porphyrins and other complementary chromophores via DNA quadruplex assembly.

Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits.

Strongyle Infection and Gut Microbiota: Profiling of Resistant and Susceptible Horses Over a Grazing Season.

Gastrointestinal strongyles are a major threat to horses' health and welfare. Given that strongyles inhabit the same niche as the gut microbiota, they may interact with each other. These beneficial or detrimental interactions are unknown in horses and could partly explain contrasted susceptibility to infection between individuals. To address these questions, an experimental pasture trial with 20 worm-free female Welsh ponies (10 susceptible (S) and 10 resistant (R) to parasite infection) was implemented for 5 months. Fecal egg counts (FEC), hematological and biochemical data, body weight and gut microbiological composition were studied in each individual after 0, 24, 43, 92 and 132 grazing days. R and S ponies displayed divergent immunological profiles and slight differences in microbiological composition under worm-free conditions. After exposure to natural infection, the predicted R ponies exhibited lower FEC after 92 and 132 grazing days, and maintained higher levels of circulating monocytes and eosinophils, while lymphocytosis persisted in S ponies. Although the overall gut microbiota diversity and structure remained similar during the parasite infection between the two groups, S ponies exhibited a reduction of bacteria such as Ruminococcus, Clostridium XIVa and members of the Lachnospiraceae family, which may have promoted a disruption of mucosal homeostasis at day 92. In line with this hypothesis, an increase in pathobionts such as Pseudomonas and Campylobacter together with changes in several predicted immunological pathways, including pathogen sensing, lipid metabolism, and activation of signal transduction that are critical for the regulation of immune system and energy homeostasis were observed in S relative to R ponies. Moreover, S ponies displayed an increase in protozoan concentrations at day 92, suggesting that strongyles and protozoa may contribute to each other's success in the equine intestines. It could also be that S individuals favor the increase of these carbohydrate-degrading microorganisms to enhance the supply of nutrients needed to fight strongyle infection. Overall, this study provides a foundation to better understand the mechanisms that underpin the relationship between equines and natural strongyle infection. The profiling of horse immune response and gut microbiota should contribute to the development of novel biomarkers for strongyle infection.