Heart Disease and Ageing: The Roles of Senescence, Mitochondria, and Telomerase in Cardiovascular Disease.

During ageing molecular damage leads to the accumulation of several hallmarks of ageing including mitochondrial dysfunction, cellular senescence, genetic instability and chronic inflammation, which contribute to the development and progression of ageing-associated diseases including cardiovascular disease. Consequently, understanding how these hallmarks of biological ageing interact with the cardiovascular system and each other is fundamental to the pursuit of improving cardiovascular health globally. This review provides an overview of our current understanding of how candidate hallmarks contribute to cardiovascular diseases such as atherosclerosis, coronary artery disease and subsequent myocardial infarction, and age-related heart failure. Further, we consider the evidence that, even in the absence of chronological age, acute cellular stress leading to accelerated biological ageing expedites cardiovascular dysfunction and impacts on cardiovascular health. Finally, we consider the opportunities that modulating hallmarks of ageing offer for the development of novel cardiovascular therapeutics.

Fasciola hepatica Cathepsin L Zymogens: Immuno-Proteomic Evidence for Highly Immunogenic Zymogen-Specific Conformational Epitopes to Support Diagnostics Development.

Fasciola hepatica, the common liver fluke and causative agent of zoonotic fasciolosis, impacts on food security with global economic losses of over $3.2 BN per annum through deterioration of animal health, productivity losses, and livestock death and is also re-emerging as a foodborne human disease. Cathepsin proteases present a major vaccine and diagnostic target of the F. hepatica excretory/secretory (ES) proteome, but utilization in diagnostics of the highly antigenic zymogen stage of these proteins is surprisingly yet to be fully exploited. Following an immuno-proteomic investigation of recombinant and native procathepsins ((r)FhpCL1), including mass spectrometric analyses (DOI: 10.6019/PXD030293), and using counterpart polyclonal antibodies to a recombinant mutant procathepsin L (anti-rFhΔpCL1), we have confirmed recombinant and native cathepsin L zymogens contain conserved, highly antigenic epitopes that are conformationally dependent. Furthermore, using diagnostic platforms, including pilot serum and fecal antigen capture enzyme-linked immunosorbent assay (ELISA) tests, the diagnostic capacities of cathepsin L zymogens were assessed and validated, offering promising efficacy as markers of infection and for monitoring treatment efficacy.

Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis.

Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in individuals with 22q11 deletion syndrome and are caused by a microdeletion on chromosome 22q11. TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key gene, when mutated, for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9-deficient mice are born with complex cardiovascular malformations that affect the outflow tract and aortic arch arteries with failure of the 3rd and 4th pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared with Tbx1 heterozygous mice. Using a novel Pax9Cre allele, we demonstrated that the site of this Tbx1-Pax9 genetic interaction is the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for crucial tissue interactions during normal morphogenesis of the pharyngeal arch artery system.

Spectral binning as an approach to post-acquisition processing of high resolution FIE-MS metabolome fingerprinting data.

INTRODUCTION: Flow infusion electrospray high resolution mass spectrometry (FIE-HRMS) fingerprinting produces complex, high dimensional data sets which require specialist in-silico software tools to process the data prior to analysis. OBJECTIVES: Present spectral binning as a pragmatic approach to post-acquisition procession of FIE-HRMS metabolome fingerprinting data. METHODS: A spectral binning approach was developed that included the elimination of single scan m/z events, the binning of spectra and the averaging of spectra across the infusion profile. The modal accurate m/z was then extracted for each bin. This approach was assessed using four different biological matrices and a mix of 31 known chemical standards analysed by FIE-HRMS using an Exactive Orbitrap. Bin purity and centrality metrics were developed to objectively assess the distribution and position of accurate m/z within an individual bin respectively. RESULTS: The optimal spectral binning width was found to be 0.01 amu. 80.8% of the extracted accurate m/z matched to predicted ionisation products of the chemical standards mix were found to have an error of below 3 ppm. The open-source R package binneR was developed as a user friendly implementation of the approach. This was able to process 100 data files using 4 Central Processing Units (CPU) workers in only 55 seconds with a maximum memory usage of 1.36 GB. CONCLUSION: Spectral binning is a fast and robust method for the post-acquisition processing of FIE-HRMS data. The open-source R package binneR allows users to efficiently process data from FIE-HRMS experiments with the resources available on a standard desktop computer.

PAX Genes in Cardiovascular Development.

The mammalian heart is a four-chambered organ with systemic and pulmonary circulations to deliver oxygenated blood to the body, and a tightly regulated genetic network exists to shape normal development of the heart and its associated major arteries. A key process during cardiovascular morphogenesis is the septation of the outflow tract which initially forms as a single vessel before separating into the aorta and pulmonary trunk. The outflow tract connects to the aortic arch arteries which are derived from the pharyngeal arch arteries. Congenital heart defects are a major cause of death and morbidity and are frequently associated with a failure to deliver oxygenated blood to the body. The Pax transcription factor family is characterised through their highly conserved paired box and DNA binding domains and are crucial in organogenesis, regulating the development of a wide range of cells, organs and tissues including the cardiovascular system. Studies altering the expression of these genes in murine models, notably Pax3 and Pax9, have found a range of cardiovascular patterning abnormalities such as interruption of the aortic arch and common arterial trunk. This suggests that these Pax genes play a crucial role in the regulatory networks governing cardiovascular development.

Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype.

BACKGROUND: Successful embryogenesis relies on the coordinated interaction between genes and tissues. The transcription factors Pax9 and Msx1 genetically interact during mouse craniofacial morphogenesis, and mice deficient for either gene display abnormal tooth and palate development. Pax9 is expressed specifically in the pharyngeal endoderm at mid-embryogenesis, and mice deficient for Pax9 on a C57Bl/6 genetic background also have cardiovascular defects affecting the outflow tract and aortic arch arteries giving double-outlet right ventricle, absent common carotid arteries and interruption of the aortic arch. RESULTS: In this study we have investigated both the effect of a different genetic background and Msx1 haploinsufficiency on the presentation of the Pax9-deficient cardiovascular phenotype. Compared to mice on a C57Bl/6 background, congenic CD1-Pax9-/- mice displayed a significantly reduced incidence of outflow tract defects but aortic arch defects were unchanged. Pax9-/- mice with Msx1 haploinsufficiency, however, have a reduced incidence of interrupted aortic arch, but more cases with cervical origins of the right subclavian artery and aortic arch, than seen in Pax9-/- mice. This alteration in arch artery defects was accompanied by a rescue in third pharyngeal arch neural crest cell migration and smooth muscle cell coverage of the third pharyngeal arch arteries. Although this change in phenotype could theoretically be compatible with post-natal survival, using tissue-specific inactivation of Pax9 to maintain correct palate development whilst inducing the cardiovascular defects was unable to prevent postnatal death in the mutant mice. Hyoid bone and thyroid cartilage formation were abnormal in Pax9-/- mice. CONCLUSIONS: Msx1 haploinsufficiency mitigates the arch artery defects in Pax9-/- mice, potentially by maintaining the survival of the 3rd arch artery through unimpaired migration of neural crest cells to the third pharyngeal arches. With the neural crest cell derived hyoid bone and thyroid cartilage also being defective in Pax9-/- mice, we speculate that the pharyngeal endoderm is a key signalling centre that impacts on neural crest cell behaviour highlighting the ability of cells in different tissues to act synergistically or antagonistically during embryo development.

Widespread winners and narrow-ranged losers: Land use homogenizes biodiversity in local assemblages worldwide.

Human use of the land (for agriculture and settlements) has a substantial negative effect on biodiversity globally. However, not all species are adversely affected by land use, and indeed, some benefit from the creation of novel habitat. Geographically rare species may be more negatively affected by land use than widespread species, but data limitations have so far prevented global multi-clade assessments of land-use effects on narrow-ranged and widespread species. We analyse a large, global database to show consistent differences in assemblage composition. Compared with natural habitat, assemblages in disturbed habitats have more widespread species on average, especially in urban areas and the tropics. All else being equal, this result means that human land use is homogenizing assemblage composition across space. Disturbed habitats show both reduced abundances of narrow-ranged species and increased abundances of widespread species. Our results are very important for biodiversity conservation because narrow-ranged species are typically at higher risk of extinction than widespread species. Furthermore, the shift to more widespread species may also affect ecosystem functioning by reducing both the contribution of rare species and the diversity of species' responses to environmental changes among local assemblages.

Global effects of land use on local terrestrial biodiversity.

Human activities, especially conversion and degradation of habitats, are causing global biodiversity declines. How local ecological assemblages are responding is less clear--a concern given their importance for many ecosystem functions and services. We analysed a terrestrial assemblage database of unprecedented geographic and taxonomic coverage to quantify local biodiversity responses to land use and related changes. Here we show that in the worst-affected habitats, these pressures reduce within-sample species richness by an average of 76.5%, total abundance by 39.5% and rarefaction-based richness by 40.3%. We estimate that, globally, these pressures have already slightly reduced average within-sample richness (by 13.6%), total abundance (10.7%) and rarefaction-based richness (8.1%), with changes showing marked spatial variation. Rapid further losses are predicted under a business-as-usual land-use scenario; within-sample richness is projected to fall by a further 3.4% globally by 2100, with losses concentrated in biodiverse but economically poor countries. Strong mitigation can deliver much more positive biodiversity changes (up to a 1.9% average increase) that are less strongly related to countries' socioeconomic status.

Arterial endoglin does not protect against arteriovenous malformations.

INTRODUCTION: Endoglin (ENG) forms a receptor complex with ALK1 in endothelial cells (ECs) to promote BMP9/10 signalling. Loss of function mutations in either ENG or ALK1 genes lead to the inherited vascular disorder hereditary haemorrhagic telangiectasia (HHT), characterised by arteriovenous malformations (AVMs). However, the vessel-specific role of ENG and ALK1 proteins in protecting against AVMs is unclear. For example, AVMs have been described to initiate in arterioles, whereas ENG is predominantly expressed in venous ECs. To investigate whether ENG has any arterial involvement in protecting against AVM formation, we specifically depleted the Eng gene in venous and capillary endothelium whilst maintaining arterial expression, and investigated how this affected the incidence and location of AVMs in comparison with pan-endothelial Eng knockdown. METHODS: Using the mouse neonatal retinal model of angiogenesis, we first established the earliest time point at which Apj-Cre-ERT2 activity was present in venous and capillary ECs but absent from arterial ECs. We then compared the incidence of AVMs following pan-endothelial or venous/capillary-specific ENG knockout. RESULTS: Activation of Apj-Cre-ERT2 with tamoxifen from postnatal day (P) 5 ensured preservation of arterial ENG protein expression. Specific loss of ENG expression in ECs of veins and capillaries led to retinal AVMs at a similar frequency to pan-endothelial loss of ENG. AVMs occurred in the proximal as well as the distal part of the retina consistent with a defect in vascular remodelling during maturation of the vasculature. CONCLUSION: Expression of ENG is not required in arterial ECs to protect against AVM formation.

Putting soil invertebrate diversity on the map.

Ecologists have had a very good foundational knowledge of the global distribution of plants and aboveground animals for many decades. But despite the immense diversity of soil organisms, our knowledge of the global distribution, drivers and threats to soil biodiversity is very limited. In this issue of Molecular Ecology, Bastida et al. (2020) produce the first global maps of soil invertebrate diversity that have been sampled at 83 locations, across six continents, using standardised methods and DNA sequencing. Using data from nematodes, arachnids and rotifers, and structural equation models, they find that diversity of these taxa is primarily driven by vegetation and climate. Given the anthropogenic changes that are occurring, and are projected to continue, this study provides important baseline information for future soil biodiversity and function monitoring, as well as exciting working hypotheses for targeted experiments.

Developing community-based urine sampling methods to deploy biomarker technology for the assessment of dietary exposure.

OBJECTIVE: Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes. DESIGN: Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements. SETTING: Urine collection methodologies were developed within home settings. PARTICIPANTS: Different cohorts of free-living volunteers. RESULTS: Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals. CONCLUSIONS: This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.

Pilot Evaluation of Two Fasciola hepatica Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics.

Fasciola hepatica, the causative agent of fasciolosis, is a global threat to public health, animal welfare, agricultural productivity, and food security. In the ongoing absence of a commercial vaccine, independent emergences of anthelmintic-resistant parasite populations worldwide are threatening the sustainability of the few flukicides presently available, and particularly triclabendazole (TCBZ) as the drug of choice. Consequently, prognoses for future fasciolosis control and sustained TCBZ application necessitate improvements in diagnostic tools to identify anthelmintic efficacy. Previously, we have shown that proteomic fingerprinting of F. hepatica excretory/secretory (ES) products offered new biomarkers associated with in vitro TCBZ-sulfoxide (SO) recovery or death. In the current paper, two of these biomarkers (calreticulin (CRT) and triose phosphate isomerase (TPI)) were recombinantly expressed and evaluated to measure TCBZ efficacy via a novel approach to decipher fluke molecular phenotypes independently of molecular parasite resistance mechanism(s), which are still not fully characterised or understood. Our findings confirmed the immunoreactivity and diagnostic potential of the present target antigens by sera from TCBZ-susceptible (TCBZ-S) and TCBZ-resistant (TCBZ-R) F. hepatica experimentally infected sheep.

Conventional land-use intensification reduces species richness and increases production: A global meta-analysis.

Most current research on land-use intensification addresses its potential to either threaten biodiversity or to boost agricultural production. However, little is known about the simultaneous effects of intensification on biodiversity and yield. To determine the responses of species richness and yield to conventional intensification, we conducted a global meta-analysis synthesizing 115 studies which collected data for both variables at the same locations. We extracted 449 cases that cover a variety of areas used for agricultural (crops, fodder) and silvicultural (wood) production. We found that, across all production systems and species groups, conventional intensification is successful in increasing yield (grand mean + 20.3%), but it also results in a loss of species richness (-8.9%). However, analysis of sub-groups revealed inconsistent results. For example, small intensification steps within low intensity systems did not affect yield or species richness. Within high-intensity systems species losses were non-significant but yield gains were substantial (+15.2%). Conventional intensification within medium intensity systems revealed the highest yield increase (+84.9%) and showed the largest loss in species richness (-22.9%). Production systems differed in their magnitude of richness response, with insignificant changes in silvicultural systems and substantial losses in crop systems (-21.2%). In addition, this meta-analysis identifies a lack of studies that collect robust biodiversity (i.e. beyond species richness) and yield data at the same sites and that provide quantitative information on land-use intensity. Our findings suggest that, in many cases, conventional land-use intensification drives a trade-off between species richness and production. However, species richness losses were often not significantly different from zero, suggesting even conventional intensification can result in yield increases without coming at the expense of biodiversity loss. These results should guide future research to close existing research gaps and to understand the circumstances required to achieve such win-win or win-no-harm situations in conventional agriculture.

A niche for ecosystem multifunctionality in global change research.

Concern about human modification of Earth's ecosystems has recently motivated ecologists to address how global change drivers will impact the simultaneous provisioning of multiple functions, termed ecosystem multifunctionality (EMF). However, metrics of EMF have often been applied in global change studies with little consideration of the information they provide beyond single functions, or how and why EMF may respond to global change drivers. Here, we critically review the current state of this rapidly expanding field and provide a conceptual framework to guide the effective incorporation of EMF in global change research. In particular, we emphasize the need for a priori identification and explicit testing of the biotic and abiotic mechanisms through which global change drivers impact EMF, as well as assessing correlations among multiple single functions because these patterns underlie shifts in EMF. While the role of biodiversity in mediating global change effects on EMF has justifiably received much attention, empirical support for effects via other biotic and physicochemical mechanisms are also needed. Studies also frequently stated the importance of measuring EMF responses to global change drivers to understand the potential consequences for multiple ecosystem services, but explicit links between measured functions and ecosystem services were missing from many such studies. While there is clear potential for EMF to provide novel insights to global change research, predictive understanding will be greatly improved by insuring future research is strongly hypothesis-driven, is designed to explicitly test multiple abiotic and biotic mechanisms, and assesses how single functions and their covariation drive emergent EMF responses to global change drivers.

Global mismatches in aboveground and belowground biodiversity.

Human activities are accelerating global biodiversity change and have resulted in severely threatened ecosystem services. A large proportion of terrestrial biodiversity is harbored by soil, but soil biodiversity has been omitted from many global biodiversity assessments and conservation actions, and understanding of global patterns of soil biodiversity remains limited. In particular, the extent to which hotspots and coldspots of aboveground and soil biodiversity overlap is not clear. We examined global patterns of these overlaps by mapping indices of aboveground (mammals, birds, amphibians, vascular plants) and soil (bacteria, fungi, macrofauna) biodiversity that we created using previously published data on species richness. Areas of mismatch between aboveground and soil biodiversity covered 27% of Earth's terrestrial surface. The temperate broadleaf and mixed forests biome had the highest proportion of grid cells with high aboveground biodiversity but low soil biodiversity, whereas the boreal and tundra biomes had intermediate soil biodiversity but low aboveground biodiversity. While more data on soil biodiversity are needed, both to cover geographic gaps and to include additional taxa, our results suggest that protecting aboveground biodiversity may not sufficiently reduce threats to soil biodiversity. Given the functional importance of soil biodiversity and the role of soils in human well-being, soil biodiversity should be considered further in policy agendas and conservation actions by adapting management practices to sustain soil biodiversity and considering soil biodiversity when designing protected areas.

Disparidades Mundiales entre la Biodiversidad Sobre y Bajo el Suelo Resumen Las actividades humanas están acelerando el cambio en la biodiversidad mundial y han tenido como resultado unos servicios ambientales severamente amenazados. Una gran proporción de la biodiversidad terrestre está albergada en el suelo, pero la biodiversidad de este ha sido omitida de varias evaluaciones mundiales de biodiversidad y de las acciones de conservación, además de que el entendimiento de los patrones mundiales de la biodiversidad del suelo permanece limitado; particularmente, la extensión del traslape entre los puntos fríos y calientes de biodiversidad sobre y bajo suelo no está clara. Examinamos los patrones mundiales de estos traslapes mapeando los índices de biodiversidad sobre el suelo (mamíferos, aves, anfibios y plantas vasculares) y bajo el suelo (bacterias, hongos y macrofauna) que creamos con datos previamente publicados de la riqueza de especies. Las áreas de disparidad entre la biodiversidad sobre y bajo el suelo cubrieron el 27% de la superficie terrestre del planeta. El bioma de los bosques templados de plantas frondosas y mixtas tuvo la proporción más alta de celdas de cuadrícula con una biodiversidad alta sobre el suelo, pero baja para en el subsuelo, mientras que los biomas boreales y de la tundra tuvieron una biodiversidad intermedia bajo el suelo, pero baja para el sobre suelo. Aunque se requieren más datos sobre la biodiversidad del suelo, tanto para cubrir los vacíos geográficos como para incluir a taxones adiciones, nuestros resultados sugieren que la protección a la biodiversidad sobre el suelo puede no reducir suficientemente las amenazas para la biodiversidad del suelo. Dada la importancia funcional de la biodiversidad del suelo y el papel de los suelos en el bienestar humano, se debería considerar a la biodiversidad del suelo mucho más en las agendas políticas y en las acciones de conservación, adaptando a las prácticas de manejo para que mantengan a la biodiversidad del suelo y la consideren cuando designen áreas protegidas.

Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA.

Splicing factor proline- and glutamine-rich (SFPQ) also commonly known as polypyrimidine tract-binding protein-associated-splicing factor (PSF) and its binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb), are highly abundant, multifunctional nuclear proteins. However, the exact role of this complex is yet to be determined. Following purification of the endogeneous SFPQ/NONO complex, mass spectrometry analysis identified a wide range of interacting proteins, including those involved in RNA processing, RNA splicing, and transcriptional regulation, consistent with a multifunctional role for SFPQ/NONO. In addition, we have identified several sites of arginine methylation in SFPQ/PSF using mass spectrometry and found that several arginines in the N-terminal domain of SFPQ/PSF are asymmetrically dimethylated. Furthermore, we find that the protein arginine N-methyltransferase, PRMT1, catalyzes this methylation in vitro and that this is antagonized by citrullination of SFPQ. Arginine methylation and citrullination of SFPQ/PSF does not affect complex formation with NONO. However, arginine methylation was shown to increase the association with mRNA in mRNP complexes in mammalian cells. Finally we show that the biochemical properties of the endogenous complex from cell lysates are significantly influenced by the ionic strength during purification. At low ionic strength, the SFPQ/NONO complex forms large heterogeneous protein assemblies or aggregates, preventing the purification of the SFPQ/NONO complex. The ability of the SFPQ/NONO complex to form varying protein assemblies, in conjunction with the effect of post-translational modifications of SFPQ modulating mRNA binding, suggests key roles affecting mRNP dynamics within the cell.

Vangl2-regulated polarisation of second heart field-derived cells is required for outflow tract lengthening during cardiac development.

Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. However, it is unclear why cells within the mesodermal heart tissue require PCP signalling. Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-bound Vangl2 marks the proximal extent of this transition zone and in the absence of Vangl2, the SHF-derived cells are abnormally polarised and disorganised. The consequent thickening, rather than lengthening, of the outflow wall leads to a shortened outflow tract. Premature down regulation of the SHF-progenitor marker Isl1 in the mutants, and accompanied premature differentiation to cardiomyocytes, suggests that the organisation of the cells within the transition zone is important for maintaining the undifferentiated phenotype. Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis.

Harmonizing Biodiversity Conservation and Productivity in the Context of Increasing Demands on Landscapes.

Biodiversity conservation and agricultural production are often seen as mutually exclusive objectives. Strategies for reconciling them are intensely debated. We argue that harmonization between biodiversity conservation and crop production can be improved by increasing our understanding of the underlying relationships between them. We provide a general conceptual framework that links biodiversity and agricultural production through the separate relationships between land use and biodiversity and between land use and production. Hypothesized relationships are derived by synthesizing existing empirical and theoretical ecological knowledge. The framework suggests nonlinear relationships caused by the multifaceted impacts of land use (composition, configuration, and intensity). We propose solutions for overcoming the apparently dichotomous aims of maximizing either biodiversity conservation or agricultural production and suggest new hypotheses that emerge from our proposed framework.

A global model of the response of tropical and sub-tropical forest biodiversity to anthropogenic pressures.

Habitat loss and degradation, driven largely by agricultural expansion and intensification, present the greatest immediate threat to biodiversity. Tropical forests harbour among the highest levels of terrestrial species diversity and are likely to experience rapid land-use change in the coming decades. Synthetic analyses of observed responses of species are useful for quantifying how land use affects biodiversity and for predicting outcomes under land-use scenarios. Previous applications of this approach have typically focused on individual taxonomic groups, analysing the average response of the whole community to changes in land use. Here, we incorporate quantitative remotely sensed data about habitats in, to our knowledge, the first worldwide synthetic analysis of how individual species in four major taxonomic groups--invertebrates, 'herptiles' (reptiles and amphibians), mammals and birds--respond to multiple human pressures in tropical and sub-tropical forests. We show significant independent impacts of land use, human vegetation offtake, forest cover and human population density on both occurrence and abundance of species, highlighting the value of analysing multiple explanatory variables simultaneously. Responses differ among the four groups considered, and--within birds and mammals--between habitat specialists and habitat generalists and between narrow-ranged and wide-ranged species.

Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates.

The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.