Fungal functional ecology: bringing a trait‐based approach to plant‐associated fungi

Fungi play many essential roles in ecosystems. They facilitate plant access to nutrients and water, serve as decay agents that cycle carbon and nutrients through the soil, water and atmosphere, and are major regulators of macro‐organismal populations. Although technological advances are improving the detection and identification of fungi, there still exist key gaps in our ecological knowledge of this kingdom, especially related to function . Trait‐based approaches have been instrumental in strengthening our understanding of plant functional ecology and, as such, provide excellent models for deepening our understanding of fungal functional ecology in ways that complement insights gained from traditional and ‐omics‐based techniques. In this review, we synthesize current knowledge of fungal functional ecology, taxonomy and systematics and introduce a novel database of fungal functional traits (Fun^Fun). Fun^Fun is built to interface with other databases to explore and predict how fungal functional diversity varies by taxonomy, guild, and other evolutionary or ecological grouping variables. To highlight how a quantitative trait‐based approach can provide new insights, we describe multiple targeted examples and end by suggesting next steps in the rapidly growing field of fungal functional ecology.     

The ecology of chronic wasting disease in wildlife

Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters' cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence.     

Metabotropic glutamate receptor subtype 7 controls maternal care,maternal motivation and maternal aggression in mice

The group III metabotropic glutamate receptor subtype 7 (mGlu7) is an important regulator of glutamatergic and GABAergic neurotransmission and known to mediate emotionality and male social behavior. However, a possible regulatory role in maternal behavior remains unknown to date. Adequate expression of maternal behavior is essential for successful rearing and healthy development of the young. By understanding genetic and neural mechanisms underlying this important prosocial behavior, we gain valuable insights into possible dysregulations. Using genetic ablation as well as pharmacological modulation, we studied various parameters of maternal behavior in two different mouse strains under the influence of mGlu7. We can clearly show a regulatory role of mGlu7 in maternal behavior. Naïve virgin female C57BL/6 mGlu7 knockout mice showed more often nursing postures and less spontaneous maternal aggression compared to their heterozygous and wildtype littermates. In lactating C57BL/6 wildtype mice, acute central activation of mGlu7 by the selective agonist AMN082 reduced arched back nursing and accelerated pup retrieval without affecting maternal aggression. In addition, in lactating CD1 wildtype mice the selective mGlu7 antagonist XAP044 increased both pup retrieval and maternal aggression. With respect to receptor expression levels, mGlu7 mRNA expression was higher in lactating vs virgin C57BL/6 mice in the prefrontal cortex, but not hypothalamus or hippocampus. In conclusion, these findings highlight a significant role of the mGlu7 receptor subtype in mediating maternal behavior in mice. Region‐dependent studies are warranted to further extend our knowledge on the specific function of the brain glutamate system in maternal behavior.     

In situ cell differentiation monitoring of Catharanthus roseus suspension culture processes by NIR spectroscopy

Bioprocess and Biosystems Engineering - Plant suspension culture is attracting interest as a promising platform to produce biological medicines due to the absence of virus, prions or DNA related to...     

Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice

Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age‐related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24–30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age‐related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF.     

The two kinds of free energy and the Bayesian revolution

The concept of free energy has its origins in 19th century thermodynamics, but has recently found its way into the behavioral and neural sciences, where it has been promoted for its wide applicability and has even been suggested as a fundamental principle of understanding intelligent behavior and brain function. We argue that there are essentially two different notions of free energy in current models of intelligent agency, that can both be considered as applications of Bayesian inference to the problem of action selection: one that appears when trading off accuracy and uncertainty based on a general maximum entropy principle, and one that formulates action selection in terms of minimizing an error measure that quantifies deviations of beliefs and policies from given reference models. The first approach provides a normative rule for action selection in the face of model uncertainty or when information processing capabilities are limited. The second approach directly aims to formulate the action selection problem as an inference problem in the context of Bayesian brain theories, also known as Active Inference in the literature. We elucidate the main ideas and discuss critical technical and conceptual issues revolving around these two notions of free energy that both claim to apply at all levels of decision-making, from the high-level deliberation of reasoning down to the low-level information processing of perception.     

An Automatable Hydrogel Culture Platform for Evaluating Efficacy of Antibody‐Based Therapeutics in Overcoming Chemoresistance

The microenvironment plays a major role in conferring chemoresistance to cancer cells. In order to better inform clinical response to chemoresistance, preclinical models that recapitulate its hallmark features are needed to enable screening for resistance‐specific therapeutic targets. A novel platform for seeding cancer cells in 3D hydrogels is presented utilizing derivatives of chitosan and alginate that, critically, is amenable to high throughput screening: cell seeding in hydrogels, media changes, dosing of anticancer compounds, and cell viability assays are all automated using a standard and commercially available liquid handling robot. Culture in these hydrogels elicits resistance in ovarian, lung, and prostate cancer cells to treatment by doxorubicin and paclitaxel. In correlation, proteomics analysis of SKOV3 cells cultured in 3D reveals enrichment of proteins associated with extreme drug resistance including HMOX1 and ALDH2. Subsequently, therapeutic antibodies targeted to tumor‐associated antigens upregulated in 3D cultures are shown to have higher efficacy compared to 2D cultures. Collectively, this automated 3D cell culture platform provides a powerful tool with utility in identification of drugs that may overcome chemoresistance.