Fine-scale time series surveys reveal new insights into spatio-temporal trends in coral cover (2002–2018), of a coral reef on the Southern Great Barrier Reef

Reef monitoring programmes often focus on limited sites, predominantly on reef slope areas, which do not capture compositional variability across zones. This study assessed spatial and temporal changes in hard coral cover at four hierarchical spatial scales. ~ 55,000, geo-referenced photoquadrats were collected annually from 2002 to 2018 and analysed using artificial intelligence for 31 sites across reef flat and reef slope zones on Heron Reef, Southern Great Barrier Reef, Australia. Trends in hard coral cover were examined at three spatial scales: (1) “reef scale”, all data; (2) “geomorphic zone scale”—north/south reef slope, inner/outer reef flat; and (3) “site scale”—31 sites. Coral cover trajectories were also examined at: (4) “sub-site scale”—sub-division of sites into 567 sub-sites, to estimate variability in coral cover trajectories via spatial statistical modelling. At reef scale coral cover increased over time to 25.6 ± 0.4 SE % in 2018 but did not recover following disturbances caused by disease (2004–2008), cyclonic conditions (2009) or severe storms (2015) to the observed pre-disturbance level (44.0 ± 0.7 SE %) seen in 2004. At geomorphic zone scale, the reef slope had significantly higher coral cover than the reef flat. Trends of decline and increase were visible in the slope zones, and the southern slope recovered to pre-decline levels. Variable coral cover trends were visible at site scale. Furthermore, sub-site spatial modelling captured eight years of coral recovery that occurred at different times and magnitudes across the four geomorphic zones, effectively estimating variability in the trajectory of the reef’s coral community. Derived spatial predictions for the entire reef show patchy coral recovery, particularly on the southern slope, and that recovery hotspots are distributed across the reef. These findings suggest that to fully understand and interpret coral decline or recovery on a reef, more accurate assessment can be achieved by examining sites distributed within different geomorphic zones to capture variation in exposure, depth and consolidation.

     

Mice with endogenous TDP‐43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis

TDP‐43 (encoded by the gene TARDBP) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP‐43 function at physiological levels both in vitro and in vivo. Interestingly, we find that mutations within the C‐terminal domain of TDP‐43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP‐43 loss‐ and gain‐of‐function effects. TDP‐43 gain‐of‐function effects in these mice reveal a novel category of splicing events controlled by TDP‐43, referred to as “skiptic” exons, in which skipping of constitutive exons causes changes in gene expression. In vivo, this gain‐of‐function mutation in endogenous Tardbp causes an adult‐onset neuromuscular phenotype accompanied by motor neuron loss and neurodegenerative changes. Furthermore, we have validated the splicing gain‐of‐function and skiptic exons in ALS patient‐derived cells. Our findings provide a novel pathogenic mechanism and highlight how TDP‐43 gain of function and loss of function affect RNA processing differently, suggesting they may act at different disease stages.     

OX40 ligation of CD4+ T cells enhances virus-specific CD8+ T cell memory responses independently of IL-2 and CD4+ T regulatory cell inhibition

We have previously shown that CD4(+) T cells are required to optimally expand viral-specific memory CD8(+) CTL responses using a human dendritic cell-T cell-based coculture system. OX40 (CD134), a 50-kDa transmembrane protein of the TNFR family, is expressed primarily on activated CD4(+) T cells. In murine models, the OX40/OX40L pathway has been shown to play a critical costimulatory role in dendritic cell/T cell interactions that may be important in promoting long-lived CD4(+) T cells, which subsequently can help CD8(+) T cell responses. The current study examined whether OX40 ligation on ex vivo CD4(+) T cells can enhance their ability to "help" virus-specific CTL responses in HIV-1-infected and -uninfected individuals. OX40 ligation of CD4(+) T cells by human OX40L-IgG1 enhanced the ex vivo expansion of HIV-1-specific and EBV-specific CTL from HIV-1-infected and -uninfected individuals, respectively. The mechanism whereby OX40 ligation enhanced help of CTL was independent of the induction of cytokines such as IL-2 or any inhibitory effect on CD4(+) T regulatory cells, but was associated with a direct effect on proliferation of CD4(+) T cells. Thus, OX40 ligation on CD4(+) T cells represents a potentially novel immunotherapeutic strategy that should be investigated to treat and prevent persistent virus infections, such as HIV-1 infection.     

Genetic diversity and conservation and utilization of plant genetic resources

Biodiversity refers to variation within the living world, while genetic diversity represents the heritable variation within and between populations of organisms, and in the context of this paper, among plant species. This pool of genetic variation within an inter-mating population is the basis for selection as well as for plant improvement. Thus, conservation of this plant genetic diversity is essential for present and future human well-being. During recent years, there has been increasing awareness of the importance of adopting a holistic view of biodiversity, including agricultural biodiversity, conservation for sustainable utilization and development. These principles have been enshrined in the Convention on Biological Diversity and the Global Plan of Action of the Food and Agriculture Organization of the United Nations. The emphasis is now to understand the distribution and extent of genetic diversity available to humans in plant species, so that the genetic diversity can be safely conserved and efficiently used. It is generally recognized that plant genetic diversity changes in time and space. The extent and distribution of genetic diversity in a plant species depends on its evolution and breeding system, ecological and geographical factors, past bottlenecks, and often by many human factors. Much of the large amount of diversity of a species may be found within individual populations, or partitioned among a number of different populations.A better understanding of genetic diversity and its distribution is essential for its conservation and use. It will help us in determining what to conserve as well as where to conserve, and will improve our understanding of the taxonomy and origin and evolution of plant species of interest. Knowledge of both these topics is essential for collecting and use of any plant species and its wild relatives. In order to mange conserved germplasm better, there is also a need to understand the genetic diversity that is present in collections. This will help us to rationalize collections and develop and adopt better protocols for regeneration of germplasm seed. Through improved characterization and development of core collections based on genetic diversity information, it will be possible to exploit the available resources in more valuable ways.     

Between plant and diurnal variation in quantities and ratios of volatile compounds emitted by Vicia faba plants

Ratios of volatile phytochemicals potentially offer a means for insects to recognise their host-plant species. However, for this to occur ratios of volatiles would need to be sufficiently consistent between plants and over time to constitute a host-characteristic cue. In this context we collected headspace samples from Vicia faba plants to determine how consistent ratios of key volatile phytochemicals used in host location by one of its insect pests, the black bean aphid, Aphis fabae, were. These were (E)-2-hexenal, (Z)-3-hexen-1-ol, 1-hexanol, benzaldehyde, 6-methyl-5-hepten-2-one, octanal, (Z)-3-hexen-1-yl acetate, (R)-linalool, methyl salicylate, decanal, undecanal, (E)-caryophyllene, (E)-β-farnesene, (S)-germacrene D, and (E, E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene, which had previously been found to be electrophysiologically and behaviourally active to A. fabae. Although the quantities of volatiles produced by V. faba showed large between plant and diurnal variation, correlations between quantities of compounds indicated that the ratios of certain pairs of volatiles were very consistent. This suggests that there is a host-characteristic cue available to A. fabae in the form of ratios of volatiles.     

Comparison of Structurally-Related Alkoxide, Amine, and Thiolate-Ligated M (M= Fe, Co) Complexes: the Influence of Thiolates on the Properties of Biologically Relevant Metal Complexes

Mechanistic pathways of metalloenzymes are controlled by the metal ion’s electronic and magnetic properties, which are tuned by the coordinated ligands. The functional advantage gained by incorporating cysteinates into the active site of non-heme iron enzymes such as superoxide reductase (SOR) is not entirely understood. Herein, we compare the structural and redox properties of a series of structurally-related thiolate, alkoxide, and amine-ligated Fe(II) complexes in order to determine how the thiolate influences properties critical to function. Thiolates are shown to reduce metal ion Lewis acidity relative to alkoxides and amines, and have a strong trans influence thereby helping to maintain an open coordination site. Comparison of the redox potentials of the structurally analogous compounds described herein shows that alkoxide ligands favor the higher-valent Fe³⁺ oxidation state, amine ligands favor the reduced Fe²⁺ oxidation state, and thiolates fall somewhere in between. These properties provide a functional advantage for substrate reducing enzymes in that they provide a site at the metal ion for substrate to bind, and a moderate potential that facilitates both substrate reduction and regeneration of the catalytically active reduced state. Redox potentials for structurally-related Co(II) complexes are shown to be cathodically-shifted relative to their Fe(II) analogues, making them ineffective reducing agents for substrates such as superoxide.     

Validation of radiocarpal joint contact models based on images from a clinical MRI scanner

This study was undertaken to assess magnetic resonance imaging (MRI)-based radiocarpal surface contact models of functional loading in a clinical MRI scanner for future in vivo studies, by comparison with experimental measures from three cadaver forearm specimens. Experimental data were acquired using a Tekscan sensor during simulated light grasp. Magnetic resonance (MR) images were used to obtain model geometry and kinematics (image registration). Peak contact pressures (PPs) and average contact pressures (APs), contact forces and contact areas were determined in the radiolunate and radioscaphoid joints. Contact area was also measured directly from MR images acquired with load and compared with model data. Based on the validation criteria (within 25% of experimental data), out of the six articulations (three specimens with two articulations each), two met the criterion for AP (0%, 14%); one for peak pressure (20%); one for contact force (5%); four for contact area with respect to experiment (8%, 13%, 19% and 23%), and three contact areas met the criterion with respect to direct measurements (14%, 21% and 21%). Absolute differences between model and experimental PPs were reasonably low (within 2.5 MPa). Overall, the results indicate that MRI-based models generated from 3T clinical MR scanner appear sufficient to obtain clinically relevant data.     

Damped-dynamics flexible fitting

In fitting atomic structures into EM maps, it often happens that the map corresponds to a different conformation of the structure. We have developed a new methodology to handle these situations that preserves the covalent geometry of the structure and allows the modeling of large deformations. The first goal is achieved by working in generalized coordinates (positional and internal coordinates), and the second by avoiding harmonic potentials. Instead, we use dampers (shock absorbers) between every pair of atoms, combined with a force field that attracts the atomic structure toward incompletely occupied regions of the EM map. The trajectory obtained by integrating the resulting equations of motion converges to a conformation that, in our validation cases, was very close to the target atomic structure. Compared to current methods, our approach is more efficient and robust against wrong solutions and to overfitting, and does not require user intervention or subjective decisions. Applications to the computation of transition pathways between known conformers, homology and loop modeling, as well as protein docking, are also discussed.     

Three novel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 isoforms. Expression, regulation, and function of the membranes of the SERCA3 family

Sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) pump Ca2+ into the endoplasmic reticulum. Recently, three human SERCA3 (h3a-c) proteins and a previously unknown rat SERCA3 (r3b/c) mRNA have been described. Here, we (i) document two novel human SERCA3 splice variants h3d and h3e, (ii) provide data for the expression and mechanisms regulating the expression of all known SERCA3 variants (r3a, r3b/c, and h3a-e), and (iii) show functional characteristics of the SERCA3 isoforms. h3d and h3e are issued from the insertion of an additional penultimate exon 22 resulting in different carboxyl termini for these variants. Distinct distribution patterns of the SERCA3 gene products were observed in a series of cell lines of hematopoietic, epithelial, embryonic origin, and several cancerous types, as well as in panels of rat and human tissues. Hypertension and protein kinase C, calcineurin, or retinoic acid receptor signaling pathways were found to differently control rat and human splice variant expression, respectively. Stable overexpression of each variant was performed in human embryonic kidney 293 cells, and the SERCA3 isoforms were fully characterized. All SERCA3 isoforms were found to pump Ca2+ with similar affinities. However, they modulated the cytosolic Ca2+ concentration ([Ca2+]c) and the endoplasmic reticulum Ca2+ content ([Ca2+]er) in different manners. A newly generated polyclonal antibody and a pan-SERCA3 antibody proved the endogenous expression of the three novel SERCA3 proteins, h3d, h3e, and r3b/c. All these data suggest that the SERCA3 gene products have a more widespread role in cellular Ca2+ signaling than previously appreciated.