Towards the general mechanistic prediction of community dynamics

”What controls the distribution and abundance of organisms”? This question, at the heart of the dynamics of ecological communities, would have been familiar to the earliest ecologists. Having lain effectively abandoned for many years, community dynamics today is a vibrant research topic of great conceptual interest with practical import for conservation, ecological management, ecosystem services and the responses of ecological communities to climate change.  We describe how modern coexistence theory can be applied to predict community dynamics through the use of demography. We explore the challenges that limit the deployment of this demographic framework, and the tools from phylogenetic and functional ecology that have been used to surmount them.  Finding existing tools not altogether sufficient, we propose the use of ‘hard’ functional traits and physiological tolerances of environmental conditions and low resource availability to extend the demographic framework so that the dynamics of a broader range of ecological communities can be accurately predicted.  We illustrate these new approaches with two case studies. Given the urgent need to accurately forecast the dynamics of ecological communities, we hope that many ecologists will adopt these tools

Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments

A novel extracellular role for tissue transglutaminase in matrix-bound VEGF-mediated angiogenesis

The importance of tissue transglutaminase (TG2) in angiogenesis is unclear and contradictory. Here we show that inhibition of extracellular TG2 protein crosslinking or downregulation of TG2 expression leads to inhibition of angiogenesis in cell culture, the aorta ring assay and in vivo models. In a human umbilical vein endothelial cell (HUVEC) co-culture model, inhibition of extracellular TG2 activity can halt the progression of angiogenesis, even when introduced after tubule formation has commenced and after addition of excess vascular endothelial growth factor (VEGF). In both cases, this leads to a significant reduction in tubule branching. Knockdown of TG2 by short hairpin (shRNA) results in inhibition of HUVEC migration and tubule formation, which can be restored by add back of wt TG2, but not by the transamidation-defective but GTP-binding mutant W241A. TG2 inhibition results in inhibition of fibronectin deposition in HUVEC monocultures with a parallel reduction in matrix-bound VEGFA, leading to a reduction in phosphorylated VEGF receptor 2 (VEGFR2) at Tyr1214 and its downstream effectors Akt and ERK1/2, and importantly its association with b1 integrin. We propose a mechanism for the involvement of matrix-bound VEGFA in angiogenesis that is dependent on extracellular TG2-related activity

Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory osteoarthritis.

Transglutaminase 2 (TG2) is highly expressed during chondrocyte maturation and contributes to the formation of a mineralised scaffold by introducing crosslinks between extracellular matrix (ECM) proteins. In healthy cartilage, TG2 stabilises integrity of ECM and likely influences cartilage stiffness and mechanistic properties. At the same time, the abnormal accumulation of TG2 in the ECM promotes chondrocyte hypertrophy and cartilage calcification, which might be an important aspect of osteoarthritis (OA) initiation. Although excessive joint loading and injuries are one of the main causes leading to OA development, it is now being recognised that the presence of inflammatory mediators accelerates OA progression. Inflammatory signalling is known to stimulate the extracellular TG2 activity in cartilage and promote TG2-catalysed crosslinking of molecules that promote chondrocyte osteoarthritic differentiation. It is, however, unclear whether TG2 activity aims to resolve or aggravate damages within the arthritic joint. Better understanding of the complex signalling pathways linking inflammation with TG2 activities is needed to identify the role of TG2 in OA and to define possible avenues for therapeutic interventions

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

p53 and TAp63 promote keratinocyte proliferation and differentiation in breeding tubercles of the zebrafish

p63 is a multi-isoform member of the p53 family of transcription factors. There is compelling genetic evidence that ΔNp63 isoforms are needed for keratinocyte proliferation and stemness in the developing vertebrate epidermis. However, the role of TAp63 isoforms is not fully understood, and TAp63 knockout mice display normal epidermal development. Here, we show that zebrafish mutants specifically lacking TAp63 isoforms, or p53, display compromised development of breeding tubercles, epidermal appendages which according to our analyses display more advanced stratification and keratinization than regular epidermis, including continuous desquamation and renewal of superficial cells by derivatives of basal keratinocytes. Defects are further enhanced in TAp63/p53 double mutants, pointing to partially redundant roles of the two related factors. Molecular analyses, treatments with chemical inhibitors and epistasis studies further reveal the existence of a linear TAp63/p53->Notch->caspase 3 pathway required both for enhanced proliferation of keratinocytes at the base of the tubercles and their subsequent differentiation in upper layers. Together, these studies identify the zebrafish breeding tubercles as specific epidermal structures sharing crucial features with the cornified mammalian epidermis. In addition, they unravel essential roles of TAp63 and p53 to promote both keratinocyte proliferation and their terminal differentiation by promoting Notch signalling and caspase 3 activity, ensuring formation and proper homeostasis of this self-renewing stratified epithelium

After Halberstam : subversion, female masculinity and the subject of heterosexuality

Because female masculinity seems to be at its most threatening when coupled with lesbian desire, [...]! concentrate on queer female masculinity almost to the exclusion of heterosexual female masculinity. I have no doubt that heterosexual female masculinity menaces gender conformity in its own way, but all too often it represents an acceptable degree of female masculinity as compared to the excessive masculinity of the dyke. Judith Halberstam: Female Masculinity. Heterosexuality has been, and continues to be, a controversial subject in feminist analyses surrounding discussions of penetrative sex, marriage, sexual violence, rape, pornography, domestic labour and representation. Although the 1990s and 2000s have witnessed the proliferation of debates and theorisations of heterosexuality in which it is interrogated and dissected, it is no longer simply condemned and dismissed as it was by early radical feminism. For early radical feminists, 'heterosexuality was the enemy to be struggled against. Its destruction was a prerequisite for the feminist revolution. Heterosexuality had to go. None of it was retrievable for feminist purposes' (Thompson in Wilkinson ;Kitzinger, 1993: 171). Nevertheless, there are traces of such thought in current theorisations of gender and sexuality. Heterosexuality has not fully shaken its legacy, and is rarely regarded as a source for celebration and subversion, and/or as exemplary for feminist politics. In this thesis, I look to the work of Lynne Segal, Stevi Jackson and Wendy Hollway who have contested and problematised radical feminist theorisations of heterosexuality. There is an emergent desire and call for more celebratory theorisations of heterosexuality whilst simultaneously there is an ongoing theoretical scepticism in the emergent queer literature. However, in the 1990s, queer theory paradoxically began to engage with the subversive potentials of heterosexuality precisely within the auspices of queer critique, which raised questions on established models of radicalism. Just as Hollway, Segal and Jackson theorised a feminist heterosexuality, ramifications were tangible in queer theory as Calvin Thomas and Segal mobilised a body of work which attempted to theorise subversive heterosexuality amidst the unproblematised celebration of non-heterosexualities. It is my intent to conduct this thesis by tracing this simultaneous celebration of nonheterosexualities and foreclosure of heterosexuality through the work of contemporary queer theory, focussing on the work of Judith 'Jack' Halberstam, author of the magnificent Female Masculinity (1998). The project intervenes in wider debates and theoretical developments that seemingly hinder radical readings of heterosexual identities, and addresses the theoretical discourses of transgression, butchness, queerness and the phallic. Can these tropes be reworked so heterosexuality can be reconfigured into a sexuality that is tolerated or even viewed as subversive by theorists, or is heterosexuality doomed to be always theoretically derided? Film: Calamity Jane (1953), Aliens (1986), Johnny Guitar( 1954) and Kill Bill Vol. I ;Vol. II (2003 ;2004)EThOS - Electronic Theses Online ServiceGBUnited Kingdo

How drought, waterlogging, and light availability shape patterns of tropical tree distributions, in French Guiana

Tropical forests display striking patterns in species richness along environmental gradients. At local scales, spatial and seasonal variation in soil-water and light availability are strongly linked to performance differences between species, and therefore compositional turnover between habitats. Understanding ecological responses to rapid environmental change is an urgent necessity in tropical forests as future tree distributions are likely to alter along lines delimiting wet and dry habitats. However, it is currently unknown what controls turnover of species between wetter and drier habitats and to what extent regeneration is controlled by the interactive effects of water and light. As field gradients of drought, waterlogging, and light rarely occur independently from one another, or indeed from other important abiotic and biotic drivers, this confounding of variables make it particularly challenging to attribute observed distributions to environmental variation. I addressed these challenges by examining seedling and sapling performance under experimental and natural conditions of drought, waterlogging and light availability, utilising the contrasting wet and dry rainforest habitats of Paracou, French Guiana, South America, as the study system. I conducted a shadehouse experiment involving seedlings of eleven co-occurring tree species with contrasting distributional patterns among the wet and dry habitats of Paracou. Using survival modelling techniques, I examined survival times of 1532 seedlings and 20,000 individual observations to investigate species variation in survival along an experimental irradiance gradient and in three contrasting water availability regimes, ‘drought’, ‘waterlogged’, and ‘watered to field capacity’. I calculated tolerance indices for drought, waterlogging, and shade based on survival time predictions, then assessed indices for evidence of interspecific trade-offs. I found evidence of non-interactive effects of water and light on seedling survival and species tolerance indices revealed a negative relationship between drought and shade tolerance. These results suggest that, when nutrients are not limiting and in the absence of root competition, shaded tropical seedlings are impacted more strongly by drought than seedlings in higher light conditions. Then, I evaluated the roles of water and light availability in governing sapling survival in the field. I used data on the survival of 5374 individual saplings of 25 species, frequency of drought and waterlogging over 24 years, and detailed information on understory light availability. Utilising Generalised Linear Mixed Modelling techniques I showed that drought was the relatively more important factor determining differential species survival, as well as a likely important role of long-term soil instability associated with topographical water availability. By comparing survival responses of species with contrasting distributions among wet and dry habitats, I was able to infer that differential survival among wet habitat associated species may filter those species from drier habitats, whereas drier habitat associated species survive better than wet associated species in the driest habitats. Finally, I used Generalised Linear Mixed Modelling techniques to assess the ability of experimentally derived species tolerances of drought, waterlogging, and shade to predict sapling performance in the field. I found evidence that abundance in topographic habitats defined by variation in water availability did depend on differential tolerance of drought, and waterlogging, but not shade. I found no evidence that sapling survival was related to any of the indices. Studies based on whole-plant tolerances can directly link plant performance to variation in resource availability and have been credited with improving the understanding of species distributions by providing mechanistic and predictive links between observed distributions and environmental conditions. This study provides positive first steps towards using shadehouse derived tolerance indices to achieve explanatory and predictive power regarding sapling performance across topographic habitats. In summary, the results presented in this thesis strongly suggest that both water limitation and waterlogging are important factors limiting species performance and therefore structuring communities along environmental gradients. Under a scenario of increasingly dry weather, the forest of Paracou may see a turnover in species composition that would lead to more drought tolerant and fewer waterlogging and shade tolerant species. In this thesis, I have focussed on plant responses to locally contrasting soil-moisture availability. However, as plant responses at this scale are ultimately responsible for distributions at large as well as finer spatial scales, these results may be applicable more widely among neotropical and other tropical forests

After Halberstam : subversion, female masculinity and the subject of heterosexuality

Because female masculinity seems to be at its most threatening whencoupled with lesbian desire, [...]! concentrate on queer female masculinityalmost to the exclusion of heterosexual female masculinity. I have no doubtthat heterosexual female masculinity menaces gender conformity in its ownway, but all too often it represents an acceptable degree of femalemasculinity as compared to the excessive masculinity of the dyke.Judith Halberstam: Female Masculinity.Heterosexuality has been, and continues to be, a controversial subject in feministanalyses surrounding discussions of penetrative sex, marriage, sexual violence, rape,pornography, domestic labour and representation. Although the 1990s and 2000s havewitnessed the proliferation of debates and theorisations of heterosexuality in which itis interrogated and dissected, it is no longer simply condemned and dismissed as itwas by early radical feminism. For early radical feminists, 'heterosexuality was theenemy to be struggled against. Its destruction was a prerequisite for the feministrevolution. Heterosexuality had to go. None of it was retrievable for feministpurposes' (Thompson in Wilkinson & Kitzinger, 1993: 171). Nevertheless, there aretraces of such thought in current theorisations of gender and sexuality.Heterosexuality has not fully shaken its legacy, and is rarely regarded as a source forcelebration and subversion, and/or as exemplary for feminist politics.In this thesis, I look to the work of Lynne Segal, Stevi Jackson and WendyHollway who have contested and problematised radical feminist theorisations ofheterosexuality. There is an emergent desire and call for more celebratorytheorisations of heterosexuality whilst simultaneously there is an ongoing theoreticalscepticism in the emergent queer literature. However, in the 1990s, queer theoryparadoxically began to engage with the subversive potentials of heterosexualityprecisely within the auspices of queer critique, which raised questions on establishedmodels of radicalism. Just as Hollway, Segal and Jackson theorised a feministheterosexuality, ramifications were tangible in queer theory as Calvin Thomas andSegal mobilised a body of work which attempted to theorise subversiveheterosexuality amidst the unproblematised celebration of non-heterosexualities. It ismy intent to conduct this thesis by tracing this simultaneous celebration of nonheterosexualitiesand foreclosure of heterosexuality through the work ofcontemporary queer theory, focussing on the work of Judith 'Jack' Halberstam, authorof the magnificent Female Masculinity (1998). The project intervenes in widerdebates and theoretical developments that seemingly hinder radical readings ofheterosexual identities, and addresses the theoretical discourses of transgression,butchness, queerness and the phallic. Can these tropes be reworked so heterosexualitycan be reconfigured into a sexuality that is tolerated or even viewed as subversive bytheorists, or is heterosexuality doomed to be always theoretically derided?Film: Calamity Jane (1953), Aliens (1986), Johnny Guitar( 1954) and Kill Bill Vol. I& Vol. II (2003 & 2004