The development of the Silurian trilobite Aulacopleura koninckii reconstructed by applying inferred growth and segmentation dynamics: A case study in paleo-evo-devo

Fossilized growth series provide rare glimpses into the development of ancient organisms, illustrating descriptively how size and shape changed through ontogeny. Occasionally fossil preservation is such that it is feasible to test alternative possibilities about how ancient development was regulated. Here we apply inferred developmental parameters pertaining to size, shape, and segmentation in the abundant and well-preserved 429 Myr old trilobite Aulacopleura koninckii that we have investigated previously to reconstruct the post-embryonic ontogeny of this ancient arthropod. Our published morphometric analyses associated with model testing have shown that: specification of the adult number of trunk segments (polymorphic in this species) was determined precociously in ontogeny; that growth regulation was targeted (i.e., compensatory), such that each developmental stage exhibited comparable variance in size and shape; and that growth gradients operating along the main body axis, both during juvenile and adult ontogeny, resulted from a form of growth control based on positional specification. While such developmental features are common among extant organisms, our results represent the oldest evidence for them within Metazoa. Herein, the novel reconstruction of the development of Aulacopleura koninckii permits visualization of patterns of relative and absolute growth and segmentation as never before possible for a fossilized arthropod ontogeny. By conducting morphometric analysis of appropriate data sets it is thus possible to move beyond descriptive ontogenetic studies and to address questions of high interest for evolutionary developmental biology using data from fossils, which can help elucidate both how developmental processes themselves evolve and how they affect the evolution of organismal body patterning. By extending similar analyses to other cases of exceptional preservation of fossilized ontogeny, we can anticipate beginning to realize the research program of “paleo-evo-devo.

Paleostrain stratigraphic analysis of calcite twins across the Cambrian-Ordovician unconformity in the Tethyan Himalaya, Spiti and Zanskar valley regions, India

Abstract Calcite strain analyses were conducted on low-grade Cambrian and Carboniferous limestone samples collected above and below the Cambrian-Ordovician unconformity in the Spiti and Zanskar valley regions of the NW Himalaya in order to compare strain patterns in rocks that bracket an enigmatic early Paleozoic tectonic episode. All samples record a layer-parallel shortening strain at a high angle to folds and faults in the Tethyan Himalayan fold-thrust belt. In the Carboniferous samples, we relate these layer-parallel strains to the onset of Cenozoic deformation within the Tethyan Himalayan fold-thrust belt. The Cambrian sample from the Spiti area contains a layer-parallel shortening strain even though the Cambrian-Ordovician unconformity is angular. This suggests that the twinning strains in the Cambrian sample may have formed at the onset of early Paleozoic folding and subsequent erosion, and that early phases of Cenozoic shortening were coaxial to early Paleozoic shortening. The maximum shortening axis in the Carboniferous samples, which is probably parallel to the early thrust transport direction in the Tethyan Himalayan fold-thrust belt, is parallel to the NE movement of India with respect to Eurasia in the Middle Eocene, suggesting that it might closely correspond to the India/Eurasian slip direction during this time period

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Study of indications for cardiac device implantation and utilisation in Fabry cardiomyopathy

Background: Fabry disease is a treatable X-linked condition leading to progressive cardiomyopathy, arrhythmia and premature death. Atrial and ventricular arrhythmias contribute significantly to adverse prognosis; however, guidance to determine which patients require cardiovascular implantable electronic devices (CIEDs) is sparse. We aimed to evaluate indications for implantation practice in the UK and quantify device utilisation. Methods: In this retrospective study, we included demographic, clinical and imaging data from patients in four of the largest UK Fabry centres. Ninety patients with Fabry disease were identified with CIEDs implanted between June 2001 and February 2018 (FD-CIED group). To investigate differences in clinical and imaging markers between those with and without devices, these patients were compared with 276 patients without a CIED (FD-control). Results: In the FD-CIED group, 92% of patients with permanent pacemakers but only 28% with implantable cardioverter-defibrillators had a class 1 indication for implantation. A further 44% of patients had defibrillators inserted for primary prevention outside of current guidance. The burden of arrhythmia requiring treatment in the FD-CIED group was high (asymptomatic atrial fibrillation: 29%; non-sustained ventricular tachycardia requiring medical therapy alone: 26%; sustained ventricular tachycardia needing anti-tachycardia pacing/defibrillation: 28%). Those with devices were older, had greater LV mass, more scar tissue and larger atrial size. Conclusions: Arrhythmias are common in Fabry patients. Those with cardiac devices had high rates of atrial fibrillation requiring anticoagulation and ventricular arrhythmia needing device treatment. These are as high as those in hypertrophic cardiomyopathy, supporting the need for Fabry-specific indications for device implantation

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study

Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD

Colonisation factor cd0873, an attractive oral vaccine candidate against clostridioides difficile

Clostridioides difficile is the main cause of health-care-associated infectious diarrhoea. Toxins, TcdA and TcdB, secreted by this bacterium damage colonic epithelial cells and in severe cases this culminates in pseudomembranous colitis, toxic megacolon and death. Vaccines in human trials have focused exclusively on the parenteral administration of toxin-based formulations. These vaccines promote toxin-neutralising serum antibodies but fail to confer protection from infection in the gut. An effective route to immunise against gut pathogens and stimulate a protective mucosal antibody response (secretory immunoglobulin A, IgA) at the infection site is the oral route. Additionally, oral immunisation generates systemic antibodies (IgG). Using this route, two different antigens were tested in the hamster model: The colonisation factor CD0873 and a TcdB fragment. Animals immunised with CD0873 generated a significantly higher titre of sIgA in intestinal fluid and IgG in serum compared to naive animals, which significantly inhibited the adherence of C. difficile to Caco-2 cells. Following challenge with a hypervirulent isolate, the CD0873-immunised group showed a mean increase of 80% in time to experimental endpoint compared to naïve animals. Survival and body condition correlated with bacterial clearance and reduced pathology in the cecum. Our findings advocate CD0873 as a promising oral vaccine candidate against C. difficile

The impacts avoided with a 1.5 °C climate target: a global and regional assessment

The 2015 Paris Agreement commits countries to pursue efforts to limit the increase in global mean temperature to 1.5 °C above pre-industrial levels. We assess the consequences of achieving this target in 2100 for the impacts that are avoided, using several indicators of impact (exposure to drought, river flooding, heat waves and demands for heating and cooling energy). The proportion of impacts that are avoided is not simply equal to the proportional reduction in temperature. At the global scale, the median proportion of projected impacts avoided by the 1.5 °C target relative to a rise of 4 °C ranges between 62 and 95% across sectors: the greatest reduction is for heat wave impacts. The 1.5 °C target results in impacts that would be between 27 and 62% lower than with the 2 °C target. For each indicator, there are differences in the proportions of impacts avoided between regions depending on exposure and the regional changes in climate (particularly precipitation). Uncertainty in the proportion of impacts that are avoided for a specific sector depends on the range in the shape of the relationship between global temperature change and impact, and this varies between sectors

The Magnitude and Duration of Late Ordovician–Early Silurian Glaciation

Understanding ancient climate changes is hampered by the inability to disentangle trends in ocean temperature from trends in continental ice volume. We used carbonate “clumped” isotope paleothermometry to constrain ocean temperatures, and thereby estimate ice volumes, through the Late Ordovician–Early Silurian glaciation. We find tropical ocean temperatures of 32° to 37°C except for short-lived cooling by ~5°C during the final Ordovician stage. Evidence for ice sheets spans much of the study interval, but the cooling pulse coincided with a glacial maximum during which ice volumes likely equaled or exceeded those of the last (Pleistocene) glacial maximum. This cooling also coincided with a large perturbation of the carbon cycle and the Late Ordovician mass extinction

Physiotherapy rehabilitation for osteoporotic vertebral fracture—a randomised controlled trial and economic evaluation (PROVE trial)

Summary The trial compared three physiotherapy approaches: manual or exercise therapy compared with a single session of physiotherapy education (SSPT) for people with osteoporotic vertebral fracture(s). At 1 year, there were no statistically significant differences between the groups meaning there is inadequate evidence to support manual or exercise therapy. Introduction To evaluate the clinical and cost-effectiveness of different physiotherapy approaches for people with osteoporotic vertebral fracture(s) (OVF). Methods >Prospective, multicentre, adaptive, three-arm randomised controlled trial. Six hundred fifteen adults with back pain, osteoporosis, and at least 1 OVF participated. Interventions: 7 individual physiotherapy sessions over 12 weeks focused on either manual therapy or home exercise compared with a single session of physiotherapy education (SSPT). The co-primary outcomes were quality of life and back muscle endurance measured by the QUALEFFO-41 and timed loaded standing (TLS) test at 12 months. Results At 12 months, there were no statistically significant differences between groups. Mean QUALEFFO-41: − 1.3 (exercise), − 0.15 (manual), and − 1.2 (SSPT), a mean difference of − 0.2 (95% CI, − 3.2 to 1.6) for exercise and 1.3 (95% CI, − 1.8 to 2.9) for manual therapy. Mean TLS: 9.8 s (exercise), 13.6 s (manual), and 4.2 s (SSPT), a mean increase of 5.8 s (95% CI, − 4.8 to 20.5) for exercise and 9.7 s (95% CI, 0.1 to 24.9) for manual therapy. Exercise provided more quality-adjusted life years than SSPT but was more expensive. At 4 months, significant changes above SSPT occurred in endurance and balance in manual therapy, and in endurance for those ≤ 70 years, in balance, mobility, and walking in exercise. Conclusions Adherence was problematic. Benefits at 4 months did not persist and at 12 months, we found no significant differences between treatments. There is inadequate evidence a short physiotherapy intervention of either manual therapy or home exercise provides long-term benefits, but arguably short-term benefits are valuable