Molecular locks and keys: the role of small molecules in phytohormone research

Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds.This work was partially funded by the National Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN-2014-06468 to Abel Rosado and funding from the Canada Research Chairs program. John Vaughan-Hirsch is funded through the BBSRC Doctoral Training Programme. Anthony Bishopp is supported by the Royal Society through a University Research Fellowship. Andrea Chini is supported by a “Ramon y Cajal” fellowship (RYC-2010-05680) and this work was partially funded the Ministerio de Economía y Competitividad project BIO2013-44407-R, the AECID AP/040886/11 and the CSIC i-COOP060. This project was supported by NSTIP strategic technologies programs, number (11-BIO-2119-02) in the Kingdom of Saudi Arabia to Andrea Chini.Peer reviewedPeer Reviewe

The role of cytokinin signalling in rice root vascular patterning

The vascular anatomy of rice roots is an important factor in drought tolerance, but little is known about the mechanisms governing its patterning. The Arabidopsis thaliana root vascular tissues are patterned by a mutually inhibitory feedback loop between auxin and cytokinin signalling (Mähönen et al. 2006). Cytokinin signalling in the procambium promotes accumulation of auxin in neighbouring cells which consequently differentiate as xylem. In these cells, high auxin levels promote expression of the pseudo-histidine phosphotransfer protein (PHP) AHP6, an inhibitor of cytokinin signalling (Bishopp et al. 2011). Whereas the root vasculature of Arabidopsis consists of a single xylem axis with phloem poles on either side, that of rice roots show a central metaxylem vessel surrounded by multiple xylem poles, between which are phloem. I hypothesised that the basic interaction between auxin and cytokinin in vascular patterning is conserved between Arabidopsis and rice, but is adapted to enable development of these different tissue patterns. Chemical treatments revealed that auxin and cytokinin are central regulators of root vascular patterning in rice, as is the case in Arabidopsis. In an effort to test whether this conservation extended to individual components of the molecular circuitry, I examined the role of the three OsPHPs, homologues of AHP6. These genes are not auxin inducible and are not able to rescue the Arabidopsis AHP6 mutant, suggesting they do not function in rice root vascular patterning. However, screening known inhibitors of cytokinin signalling for in auxin inducibility in the root tip revealed a subset of the type-A RRs (OsRR1, OsRR6 and OsRR7) are auxin inducible, and were able to rescue the Arabidopsis ahp6 mutant, suggesting these genes may have been recruited to function in the hormonal crosstalk regulating root vascular patterning. Phylogenetic analyses revealed a single amino acid substitution in a conserved region of the PHPs which differs between the dicots and the monocots. To directly determine activity of the OsPHPs, and the relevance of these substitutions, in-vitro phosphotransfer assays were performed. Preliminary results suggest these substitutions do not affect protein function. To characterise candidate genes, transcriptional reporters and mutant plants were generated. Reporters show expression of most candidate genes in the root, with some localised to root protoxylem. Mutants were generated using CRISPR and homozygous and heterozygous mutants were identified. Together, results described here give insight into how regulatory networks may be adapted to bring about differing responses

The role of cytokinin signalling in rice root vascular patterning

The vascular anatomy of rice roots is an important factor in drought tolerance, but little is known about the mechanisms governing its patterning. The Arabidopsis thaliana root vascular tissues are patterned by a mutually inhibitory feedback loop between auxin and cytokinin signalling (Mähönen et al. 2006). Cytokinin signalling in the procambium promotes accumulation of auxin in neighbouring cells which consequently differentiate as xylem. In these cells, high auxin levels promote expression of the pseudo-histidine phosphotransfer protein (PHP) AHP6, an inhibitor of cytokinin signalling (Bishopp et al. 2011). Whereas the root vasculature of Arabidopsis consists of a single xylem axis with phloem poles on either side, that of rice roots show a central metaxylem vessel surrounded by multiple xylem poles, between which are phloem. I hypothesised that the basic interaction between auxin and cytokinin in vascular patterning is conserved between Arabidopsis and rice, but is adapted to enable development of these different tissue patterns. Chemical treatments revealed that auxin and cytokinin are central regulators of root vascular patterning in rice, as is the case in Arabidopsis. In an effort to test whether this conservation extended to individual components of the molecular circuitry, I examined the role of the three OsPHPs, homologues of AHP6. These genes are not auxin inducible and are not able to rescue the Arabidopsis AHP6 mutant, suggesting they do not function in rice root vascular patterning. However, screening known inhibitors of cytokinin signalling for in auxin inducibility in the root tip revealed a subset of the type-A RRs (OsRR1, OsRR6 and OsRR7) are auxin inducible, and were able to rescue the Arabidopsis ahp6 mutant, suggesting these genes may have been recruited to function in the hormonal crosstalk regulating root vascular patterning. Phylogenetic analyses revealed a single amino acid substitution in a conserved region of the PHPs which differs between the dicots and the monocots. To directly determine activity of the OsPHPs, and the relevance of these substitutions, in-vitro phosphotransfer assays were performed. Preliminary results suggest these substitutions do not affect protein function. To characterise candidate genes, transcriptional reporters and mutant plants were generated. Reporters show expression of most candidate genes in the root, with some localised to root protoxylem. Mutants were generated using CRISPR and homozygous and heterozygous mutants were identified. Together, results described here give insight into how regulatory networks may be adapted to bring about differing responses

Mid-Pleistocene thin-skinned glaciotectonic thrusting of the Aberdeen Ground Formation, Central Graben region, central North Sea

This paper presents the results of a high-resolution 2D seismic survey of mid-Pleistocene glaciogenic sediments in the Central Graben region of the central North Sea. Sediments have undergone major glaciotectonic thrusting and folding associated with the repeated southerly advance of a mid-Pleistocene ice sheet. The total observed length of the thrust-stacked section is approximately 5–6 km, comprising a series of discrete thrust slices, which range in length from  700 m. The basal detachment of the thrust complex occurs at a depth of ca. 220 m below the sea bed within the upper Aberdeen Ground Formation. A thin-skinned glaciotectonic model involving proglacial to ice-marginal glaciotectonic thrusting followed by post-tectonic deposition is proposed. Initial ice advance led to the over-pressurizing of groundwater within a laterally extensive sand sheet in the upper Aberdeen Ground Formation, promoting the formation of a major décollement surface at the base of the developing thrust-stack. Over-pressurization of the groundwater system is thought to have occurred in response to rapid ice advance, suggesting that the development of large-scale thrust complexes may be associated with surge-type behaviour. The proposed model evidences complex dynamics of mid-Pleistocene ice sheets within the central North Sea

North, east, south, west: mapping vascular tissues onto the Arabidopsis root

The Arabidopsis root has provided an excellent model for understanding patterning processes and cell fate specification. Vascular patterning represents an especially interesting process, as new positional information must be generated to transform an approximately radially symmetric root pole into a bisymmetric structure with a single xylem axis. This process requires both growth of the embryonic tissue alongside the subsequent patterning. Recently researchers have identified a series of transcription factors that modulate cell divisions to control vascular tissues growth. Spatial regulation in the signalling of two hormones, auxin and cytokinin, combine with other transcription factors to pattern the xylem axis. We are now witnessing the discovery of increasingly complex interactions between these hormones that can be interpreted through the use of mathematical models

Reintroduced White Storks ( Ciconia ciconia ) Have Similar Diets to Their Wild Conspecifics

Understanding a species' diet is crucial for assessing its ecology and can indicate the success of reintroduction efforts. We explored dietary composition and compared pellet morphology and supplementary prey proportions between two white stork (Ciconia ciconia) groups to assess reintroduction effectiveness. White stork groups consisted of released individuals that were free flying (i.e., “wild group”) and those kept within a confined enclosure (“captive group”). A total of 23 white stork pellets were collected during the 2023 breeding season. Wild group pellets were significantly heavier ((Formula presented.) = 12.7 ± 9.2 g [SD]) than captive group pellets ((Formula presented.) = 5.2 ± 2.1 g). As expected, all captive group pellets contained supplementary prey, accounting for 88.4% ± 26.1% of pellet biomass, whereas 73.3% of wild group pellets contained supplementary prey, comprising 52.9% ± 36.3% of pellet biomass. The wild group predominantly foraged on beetles (Coleoptera) and earthworms (Clitellata). Our results represent the first quantitative dietary assessment of reintroduced white storks in southern England. Similarities between our data and that of wild white stork diets from elsewhere in their range suggest successful post-release acclimatisation at Knepp Estate.</p

The Middle Pleistocene glacial evolution of northern East Anglia, UK: a dynamic tectonostratigraphic-parasequence approach

The Middle Pleistocene glacial history of northern East Anglia is a controversial topic with differing opinions surrounding chronology, provenance and the relative stratigraphic framework. Reconciling the stratigraphic framework of the region is an essential first step to developing onshore–offshore geological models and a robust event-driven chronological framework. Within this study a dynamic tectonostratigraphic–parasequence methodology is applied to deposits traditionally attributed to the Anglian Glaciation (Marine Isotope Stage 12). This approach offers an insight into ice-bed coupling during glaciation and how evolving boundary conditions influenced glacier dynamics. Six major tectonostratigraphic–parasequence assemblages (A1–A6) are recognized in northern East Anglia and correlate with successive advances into the region of North Sea or Pennine lobes of the British Ice Sheet. Individual tectonostratigraphic–parasequence assemblages are bound at their base by a sedimentary contact or, more commonly, a glacitectonic zone. The geometry and structural characteristics of these glacitectonic zones reflect temporal and spatial variations in ice-bed coupling (traction), a function of substrate rheology and, in turn, variations in lithology, porewater availability and thermo-mechanical properties. The role of permafrost may also be significant, promoting proglacial/ice-marginal thrust stacking in front of advancing ice and enhanced ice-bed decoupling during subsequent overriding and subglacial till accretio

Macaque models of human infectious disease.

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease

Understanding the relationship between suicidality, current depressed mood, personality, and cognitive factors

Objectives: Links between suicidality and depressed mood are well established. There is, however, little information about the emotional regulation processes that underlie the relationship between suicidality and current low mood, and how these processes differ between groups of never-suicidal (NS), suicidal ideators, and suicide attempters. As suicidality and depression are heterogeneous constructs, this study aimed to conduct within- and between-group comparisons of known suicide risk factors that are associated with emotion regulation (neuroticism, trait aggression, brooding, impulsivity, and overgeneral autobiographical memories). Design: Correlational design using between- and within-group comparisons from self-report measures. Methods: Inter- and intragroup differences were identified using Pearson's correlation coefficients and tests of difference. An analysis of indirect effects was used to investigate whether the relationship between suicidality and current low mood was mediated by neuroticism, trait aggression, brooding, impulsivity, and overgeneral autobiographical memories, and if this relationship varied according to group type. Results:  Brooding appeared to be a consistent feature of all three groups and was closely related to current low mood. Compared to the NS group, the relationship between suicide attempts and current low mood showed greater associations with brooding, trait aggression, and overgeneral autobiographical memories. Compared to the NS group, the suicidal ideation group showed stronger associations with neuroticism and impulsivity, but these factors did not correlate with low mood. Conclusion: These results suggest a need for larger studies to focus on heterogeneity within suicidal populations and consider how different combinations of risk factors may heighten or reduce suicide risk. Practitioner points: * It is well known that the severity and intensity of suicide and depressed presentations vary because of underlying dispositional and contextual factors (Fried & Nesse, ) which, in turn, affect how events are interpreted and responded to. Despite this, there is little research about how these mechanisms operate in different types of suicide groups, and their influence on the relationship between suicidality and current low mood. * Understanding interrelationships that affect current low mood is of clinical significance because past suicidal history and deteriorations in already negative mood are linked to repeated suicide attempts and completion. * Our findings show that ruminative brooding, defined as a tendency to repeatedly think about emotional aspects of an event, consistently correlates with current low mood across different types of suicidal groups (NS, suicidal ideators, and suicide attempters), and across analyses. * Findings also show that suicidal ideation and attempt groups were associated with specific personality characteristics that increased the propensity of emotional responding and interpretation compared to the NS group. The relationship between suicide attempt and current low mood had a higher propensity to be influenced by trait aggression, brooding, and overgenerality compared to the NS group. In contrast, although the suicidal ideation group correlated more strongly with neuroticism and impulsivity, these factors did not influence current low mood. * In terms of clinical practice, these findings imply that specific styles of interpretation and thinking may maintain the relationship between suicidality and current low mood. Given the cross-sectional nature of the study, however, it is not possible to imply causality. Nevertheless, the findings obtained provide some support for transdiagnostic models of cognitive-behavioural processes that could be developed further.PostprintPeer reviewe

Orientalising deafness: race and disability in imperial Britain

This article explores the conflations and connections that postcolonial and disability scholars have drawn between ‘race’, ‘colonialism’ and ‘disability’ from a historical perspective. By looking at the connections drawn between ‘race’ and ‘disability’ in the context of nineteenth-century imperial Britain, I hope to probe beyond them to examine the origins and implications of their interplay. I do so by focusing on ideas about deafness, an impairment radically reconfigured in the colonial period, and inflected with concerns about degeneration, belonging, heredity and difference. Disability, I argue, not only operated as an additional ‘category of difference’ alongside ‘race’ as a way of categorising and subjugating the various ‘others’ of Empire, but intersected with it. The ‘colonisation’ of disabled people in Britain and the ‘racial other’ by the British were not simply simultaneous processes or even analogous ones, but were part and parcel of the same cultural and discursive system. The colonising context of the nineteenth century, a period when British political, economic and cultural expansion over areas of South Asia, Australasia and Africa increased markedly, structured the way in which all forms of difference were recognised and expressed, including the difference of deafness. So too did the shifts in the raced and gendered thinking that accompanied it, as new forms of knowledge were developed to justify, explain and contest Britain's global position and new languages were developed through which to articulate otherness. Such developments reconfigured the meaning of disability. Disability was, in effect, ‘orientalised’. ‘Race’ I argue was formative in shaping what we have come to understand as ‘disability’ and vice versa; they were related fantasies of difference