The disentangled bank: how loss of habitat fragments and disassembles ecological networks

Habitat transformation is one of the leading causes of changes in biodiversity and the breakdown of ecosystem function and services. The impacts of habitat transformation on biodiversity are complex and can be difficult to test and demonstrate. Network approaches to biodiversity science have provided a powerful set of tools and models that are beginning to present new insight into the structural and functional effects of habitat transformation on complex ecological systems. We propose a framework for studying the ways in which habitat loss and fragmentation jointly affect biodiversity by altering both habitat and ecological interaction networks. That is, the explicit study of "networks of networks" is required to understand the impacts of habitat change on biodiversity. We conduct a broad review of network methods and results, with the aim of revealing the common approaches used by landscape ecology and community ecology. We find that while a lot is known about the consequences of habitat transformation for habitat network topology and for the structure and function of simple antagonistic and mutualistic interaction networks, few studies have evaluated the consequences for large interaction networks with complex and spatially explicit architectures. Moreover, almost no studies have been focused on the continuous feedback between the spatial structure and dynamics of the habitat network and the structure and dynamics of the interaction networks inhabiting the habitat network. We conclude that theory and experiments that tackle the ecology of networks of networks are needed to provide a deeper understanding of biodiversity change in fragmented landscapes.     

Does the failure to acquire helminthic parasites predispose to Crohn's disease?

Two polarized patterns (Th1 and Th2) of cytokines regulate inflammatory responses. Each cytokine pattern inhibits production of the opposing pattern. Lymphocytes from inflamed intestine due to Crohn's disease secrete a Th1 pattern of cytokines. Crohn's disease is most prevalent in highly industrialized countries with temperate climates. It occurs rarely in tropical third world countries with poor sanitation. We propose that exposure to an environmental agent predisposes individuals to Crohn's disease. Parasitic worms (helminths) are common in tropical climates and in populations subject to crowding and poor sanitation. Children are most subject to helminthic colonization. Many helminths live within or migrate through the human gut where they interact with the mucosal immune system. The host mounts a mucosal response that includes Th2 cytokine production limiting helminthic colonization. Helminths and their eggs probably are the most potent stimulators of mucosal Th2 responses. The Th2 response provoked by parasitic worms can modulate immune reactions to unrelated parasitic, bacterial, and viral infections. Many people in developed countries now live in increasingly hygienic environments, avoiding exposure to helminths. Perhaps failure to acquire these parasites and experience mucosal Th2 conditioning predisposes to Crohn's disease, which is an overly active Th1 inflammation.     

Disease pathways at the Rat Genome Database Pathway Portal: genes in context-a network approach to understanding the molecular mechanisms of disease

Background

Biological systems are exquisitely poised to respond and adjust to challenges, including damage. However, sustained damage can overcome the ability of the system to adjust and result in a disease phenotype, its underpinnings many times elusive. Unraveling the molecular mechanisms of systems biology, of how and why it falters, is essential for delineating the details of the path(s) leading to the diseased state and for designing strategies to revert its progression. An important aspect of this process is not only to define the function of a gene but to identify the context within which gene functions act. It is within the network, or pathway context, that the function of a gene fulfills its ultimate biological role. Resolving the extent to which defective function(s) affect the proceedings of pathway(s) and how altered pathways merge into overpowering the system's defense machinery are key to understanding the molecular aspects of disease and envisioning ways to counteract it. A network-centric approach to diseases is increasingly being considered in current research. It also underlies the deployment of disease pathways at the Rat Genome Database Pathway Portal. The portal is presented with an emphasis on disease and altered pathways, associated drug pathways, pathway suites, and suite networks.

Results

The Pathway Portal at the Rat Genome Database (RGD) provides an ever-increasing collection of interactive pathway diagrams and associated annotations for metabolic, signaling, regulatory, and drug pathways, including disease and altered pathways. A disease pathway is viewed from the perspective of networks whose alterations are manifested in the affected phenotype. The Pathway Ontology (PW), built and maintained at RGD, facilitates the annotations of genes, the deployment of pathway diagrams, and provides an overall navigational tool. Pathways that revolve around a common concept and are globally connected are presented within pathway suites; a suite network combines two or more pathway suites.

Conclusions

The Pathway Portal is a rich resource that offers a range of pathway data and visualization, including disease pathways and related pathway suites. Viewing a disease pathway from the perspective of underlying altered pathways is an aid for dissecting the molecular mechanisms of disease.

     

How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis?

Background

Lymphatic vessels are major routes for metastasis in head and neck squamous cell carcinoma (HNSCC), but lymphatic endothelial cells (LECs) are difficult to recognize in tumor histological sections. D2-40 stains podoplanin, a molecule expressed in LECs, however, the potential prognostic usefulness of this molecule is not completely understood in HNSCC. We aimed to investigate the value of assessing peritumoral and intratumoral lymphatic vessel density (LVD) as prognostic marker for HNSCC.

Methods

Thirty-one cases of HNSCC were stained for D2-40 and CD31. LVD and blood vessel density (BVD) were assessed by counting positive reactions in 10 hotspot areas at ×200 magnification.

Results

D2-40 was specific for lymphatic vessels and did not stain blood vascular endothelial cells. LECs showed more tortuous and disorganized structure in intratumoral lymphatic vessels than in peritumoral ones. No statistical differences were observed between peritumoral-LVD and intratumoral-LVD or between peritumoral-BVD and intratumoral-BVD. Tumor D2-40 staining was positively associated with lymphatic vessel invasion (p = 0.011).

Conclusion

LVD is a powerful marker for HNSCC prognosis. We found significant differences in peritumoral and intratumoral D2-40 immunoreactivity, which could have important implications in future therapeutic strategies and outcome evaluation.

     

Kinetic modeling as a tool to understand the influence of cell culture process parameters on the glycation of monoclonal antibody biotherapeutics

Glycation, the nonenzymatic reaction between the reducing sugar glucose and the primary amine residues on amino acid side chains, commonly occurs in the cell culture supernatant during production of therapeutic monoclonal antibodies (mAbs). While glycation has the potential to impact efficacy and pharmacokinetic properties for mAbs, the most common undesirable impact of glycation is on the distribution of charged species, often a release specification for commercial processes. Existing empirical approaches are usually insufficient to rationalize the effects of cell line and process changes on glycation. To address this gap, we developed a kinetic model for estimating mAb glycation levels during the cell culture process. The rate constant for glycation, including temperature and pH dependence, was estimated by fitting the kinetic model to time-course glycation data from bioreactors operated at different process settings that yielded a wide range of glycation values. The parameter values were further validated by independently estimating glycation rate constants using cell-free incubation studies at various temperatures. The model was applied to another mAb, by re-estimating the activation energy to account for effect of a glycation “hotspot”. The model was further utilized to study the role of temperature shift as an approach to reduce glycation levels in the manufacturing process for mAb2. While a downshift in temperature resulted in lowering of glycation levels for mAb2, the model helped elucidate that this effect was caused due to contribution from changes in glucose consumption, mAb secretion and temperature, instead of a direct impact of temperature alone on the kinetic rate of glycation.     

Onchocerca volvulus-specific antibody and cellular responses in onchocerciasis patients treated annually with ivermectin for 30 years and exposed to parasite transmission in central Togo

BackgroundAnnual mass drug administrations (MDA) of ivermectin will strongly reduce Onchocerca volvulus microfilariae (mf) in the skin and in the onchocerciasis patients’ eyes. Ivermectin treatment will also affect the expression of immunity in patients, such that activated immune defenses may help control and contribute to clearance of mf of O. volvulus. Longitudinal surveys are a prerequisite to determining the impact of ivermectin on the status of anti-parasite immunity, notably in risk zones where parasite transmission and active O. volvulus infections persist.Methodology/Principal findingsOnchocerciasis patients were treated annually with ivermectin and their Onchocerca volvulus antigen (OvAg) specific IgG and cellular responses were investigated before and at 30 years post initial ivermectin treatment (30yPT).Repeated annual ivermectin treatments eliminated persisting O. volvulus microfilariae (mf) from the skin of patients and abrogated patent infections. The OvAg-specific IgG1 and IgG4 responses were diminished at 30yPT to the levels observed in endemic controls. Prior to starting ivermectin treatment, OvAg-induced cellular productions of IL-10, IFN-γ, CCL13, CCL17 and CCL18 were low in patients, and at 30yPT, cellular cytokine and chemokine responses increased to the levels observed in endemic controls. In contrast, mitogen(PHA)- induced IL-10, IFN-γ, CCL17 and CCL18 cellular production was diminished. This divergent response profile thus revealed increased parasite antigen-specific but reduced polyclonal cellular responsiveness in patients. The transmission of O. volvulus continued at the patients’ location in the Mô river basin in central Togo 2018 and 2019 when 0.58% and 0.45%, respectively, of Simulium damnosum s.l. vector blackflies carried O. volvulus infections.Conclusions/SignificanceRepeated annual ivermectin treatment of onchocerciasis patients durably inhibited their patent O. volvulus infections despite ongoing low-level parasite transmission in the study area. Repeated MDA with ivermectin affects the expression of immunity in patients. O. volvulus parasite-specific antibody levels diminished to levels seen in infection-free endemic controls. With low antibody levels, antibody-dependent cellular cytotoxic responses against tissue-dwelling O. volvulus larvae will weaken. O. volvulus antigen inducible cytokine and chemokine production increased in treated mf-negative patients, while their innate responsiveness to mitogen declined. Such lower innate responsiveness in elderly patients could contribute to reduced adaptive immune responses to parasite infections and vaccines. On the other hand, increased specific cellular chemokine responses in mf-negative onchocerciasis patients could reflect effector cell activation against tissue invasive larval stages of O. volvulus. The annual Simulium damnosum s.l. biting rate observed in the Mô river basin was similar to levels prior to initiation of MDA with ivermectin, and the positive rtPCR results reported here confirm ongoing O. volvulus transmission.     

Nested patterns of community assembly in the colonisation of artificial canopy habitats by oribatid mites

An observed species–area relationship (SAR) in assemblages of oribatid mites inhabiting natural canopy habitats (suspended soils) led to an experimental investigation of how patch size, height in canopy and moisture influence the species richness, abundance and community composition of arboreal oribatid mites. Colonisation by oribatid mites on 90 artificial canopy habitats (ACHs) of three sizes placed at each of three heights on the trunks of ten western redcedar trees was recorded over a 1‐year period. Fifty‐nine oribatid mite species colonised the ACHs, and richness increased with the moisture content and size of the habitat patch. Oribatid mite species richness and abundance, and ACH moisture content decreased with increasing ACH height in the canopy. Patterns in the species richness and community composition of ACHs were non‐random and demonstrated a significant nested pattern. Correlations of patch size, canopy height and moisture content with community nestedness suggest that species‐specific environmental tolerances combined with the differential dispersal abilities of species contributed to the non‐random patterns of composition in these habitats. In line with the prediction that niche‐selection filters out species from the regional pool that cannot tolerate environmental harshness, moisture‐stressed ACHs in the high canopy had lower community variability than ACHs in the lower canopy. Colonising source pools to ACHs were almost exclusively naturally‐occurring canopy sources, but low levels of colonisation from the forest floor were apparent at low heights within the ACH system. We conclude that stochastic dispersal dynamics within the canopy are crucial to understanding oribatid mite community structure in suspended soils, but that the relative importance of stochastic dispersal assembly may be dependent on a strong deterministic element to the environmental tolerances of individual species which drives non‐random patterns of community assembly.     

Traits explain community disassembly and trophic contraction following experimental environmental change

Many ecosystems are currently undergoing dramatic changes in biodiversity due to habitat loss and climate change. Responses to global change at the community level are poorly understood, as are the impacts of community disassembly on ecosystem‐level processes. Uncertainties remain regarding the patterns of extirpation and persistence under single vs. multiple forms of environmental change. Here, we use a trait‐based and food web approach to examine the effects of experimentally changing moisture, temperature and habitat ‘openness’ on a functionally important group of microarthropods associated with a boreal forest floor bryosphere (detrital moss) system. Overall, the outcome of community disassembly was mediated by the correlation between our environmental factors and species traits, particularly body size. Minor increases in summer temperatures maintained greater species richness, whereas drought stress had a significant negative effect on community‐level abundance and richness. These effects were reflected in modifications to the community‐wide body‐size spectra. Habitat openness alleviated biodiversity loss in the larger‐bodied species of the most abundant taxonomic group, but did not fully mitigate the effects of drought. The most striking result of this experiment was an overall contraction of the food web among persistent species under drought stress (i.e. those not extirpated by environmental change). These results suggest that major changes in boreal microarthropod community structure are likely to occur in response to common forms of global change. Moreover, the contraction in trophic structure even amongst tolerant species suggests that ecosystem function within the bryosphere can be altered by environmental change.     

Heterologous expression in <Emphasis Type="Italic">Tritrichomonas foetus</Emphasis> of functional <Emphasis Type="Italic">Trichomonas vaginalis</Emphasis> AP65 adhesin

Background  

Trichomonosis, caused by Trichomonas vaginalis, is the number one, nonviral sexually transmitted infection that has adverse consequences for the health of women and children. The interaction of T. vaginalis with vaginal epithelial cells (VECs), a step preparatory to infection, is mediated in part by the prominent surface protein AP65. The bovine trichomonad, Tritrichomonas foetus, adheres poorly to human VECs. Thus, we established a transfection system for heterologous expression of the T. vaginalis AP65 in T. foetus, as an alternative approach to confirm adhesin function for this virulence factor.