Metabolomic changes in Mycobacterium avium subsp. paratuberculosis (MAP) challenged Holstein–Friesian cattle highlight the role of serum amino acids as indicators of immune system activation

INTRODUCTION: Paratuberculosis, commonly known as Johne’s disease, is a chronic granulomatous infection of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Clinical signs, including reduced milk yields, weight loss and diarrhoea, are typically absent until 2 to 6 years post exposure. OBJECTIVES: To identify metabolomic changes profiles of MAP challenged Holstein–Friesian (HF) cattle and correlate identified metabolites to haematological and immunological parameters. METHODS: At approximately 6 weeks of age, calves (n = 9) were challenged with 3.8 × 10(9) cells of MAP (clinical isolate CIT003) on 2 consecutive days. Additional unchallenged calves (n = 9) formed the control group. The study used biobanked serum from cattle sampled periodically from 3- to 33-months post challenge. The assessment of sera using flow infusion electrospray high resolution mass spectrometry (FIE-HRMS) for high throughput, sensitive, non-targeted metabolite fingerprinting highlighted differences in metabolite levels between the two groups. RESULTS: In total, 25 metabolites which were differentially accumulated in MAP challenged cattle were identified, including 20 which displayed correlation to haematology parameters, particularly monocyte levels. CONCLUSION: The targeted metabolites suggest shifts in amino acid metabolism that could reflect immune system activation linked to MAP and as well as differences in phosphocholine levels which could reflect activation of the Th1 (tending towards pro-inflammatory) immune response. If verified by future work, selected metabolites could be used as biomarkers to diagnose and manage MAP infected cattle. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11306-022-01876-w

Effects of age and symptomatology on cortical thickness in autism spectrum disorders

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours. © 2012 Elsevier Ltd. All rights reserved

The Local Group dwarf Leo T: HI on the brink of star formation

We present Giant Meterwave Radio Telescope (GMRT) and Westerbork ynthesis Radio Telescope (WSRT) observations of the recently discovered Local Group dwarf galaxy, Leo T. The peak HI column density is measured to be 7x10^20 cm^-2, and the total HI mass is 2.8Xx10^5 Msun, based on a distance of 420 kpc. Leo T has both cold (~ 500 K) and warm (~ 6000 K) HI at its core, with a global velocity dispersion of 6.9 km/s, from which we derive a dynamical mass within the HI radius of 3.3x10^6 Msun, and a mass-to-light ratio of greater than 50. We calculate the Jeans mass from the radial profiles of the HI column density and velocity dispersion, and predict that the gas should be globally stable against star formation. This finding is inconsistent with the half light radius of Leo T, which extends to 170 pc, and indicates that local conditions must determine where star formation takes place. Leo T is not only the lowest luminosity galaxy with on-going star formation discovered to date, it is also the most dark matter dominated, gas-rich dwarf in the Local Group.Comment: 6 pages, 7 figures, accepted for publication in MNRAS on November 15th 2007, full resolution version at: http://www.ast.cam.ac.uk/~eryan/leot.pdf . Typographical error in sound speed equation has led to a new Figure 6 and minor changes to the tex

The representation of soil moisture-atmosphere feedbacks across the Tibetan Plateau in CMIP6

Thermal processes on the Tibetan Plateau (TP) influence atmospheric conditions on regional- and global-scales. Given this, previous work has shown that soil moisture-driven surface flux variations feed back onto the atmosphere. Whilst soil moisture is a source of atmospheric predictability, no study has evaluated soil moisture-atmosphere coupling on the TP in general circulation models (GCMs). In this study we use several analysis techniques to assess soil moisture-atmosphere coupling in Coupled Model Intercomparison Project phase 6 (CMIP6) simulations including: instantaneous coupling indices; analysis of flux and atmospheric behaviour during dry spells; and a quantification of the preference for convection over drier soils. Through these metrics we partition feedbacks into their atmospheric and terrestrial components. Consistent with previous global studies, we conclude substantial inter-model differences in the representation of soil moisture-atmosphere coupling, and that most models underestimate such feedbacks. Focusing on dry spell analysis, most models underestimate increased sensible heat during periods of rainfall deficiency. For example, the model-mean bias in anomalous sensible heat flux is 10 W m−2 (≈ 25%) smaller compared to observations. Deficient dry-spell sensible heat fluxes lead to a weaker atmospheric response. We also find that most GCMs fail to capture the negative feedback between soil moisture and deep convection. The poor simulation of feedbacks in CMIP6 experiments suggests that forecast models also struggle to exploit soil moisture-driven predictability. To improve the representation of land-atmosphere feedbacks requires developments in not only atmospheric modelling, but also surface processes, as we find weak relationships between rainfall biases and coupling indexes

Clinical relevance of biomarkers of oxidative stress

SIGNIFICANCE Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000

Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review

Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern. Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care. Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research. Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements. Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Technical Performance Reduces during the Extra-Time Period of Professional Soccer Match-Play

Despite the importance of extra-time in determining progression in specific soccer tournament matches, few studies have profiled the demands of 120-minutes of soccer match-play. With a specific focus on the extra-time period, and using a within-match approach, we examined the influence of prolonged durations of professional soccer match-play on markers of technical (i.e., skilled) performance. In 18 matches involving professional European teams played between 2010 and 2014, this retrospective study quantified the technical actions observed during eight 15-minute epochs (E1: 00:00–14:59 min, E2: 15:00-29:59 min, E3: 30:00-44:59 min, E4: 45:00-59:59 min, E5: 60:00-74:59 min, E6: 75:00-89:59 min, E7: 90:00-104:59 min, E8: 105:00-119:59 min). Analysis of players who completed the demands of the full 120 min of match-play revealed that the cumulative number of successful passes observed during E8 (61±23) was lower than E1-4 (E1: 88±23, P=0.001; E2: 77±21, P=0.005; E3: 79±18, P=0.001; E4: 80±21, P=0.001) and E7 (73±20, P=0.002). Similarly, the total number of passes made in E8 (71±25) was reduced when compared to E1 (102±22, P=0.001), E3 (91±19, P=0.002), E4 (93±22, P≤0.0005) and E7 (84±20, P=0.001). The cumulative number of successful dribbles reduced in E8 (9±4) when compared to E1 (14±4, P=0.001) and E3 (12±4, P≤0.0005) and the total time the ball was in play was less in E8 (504±61 s) compared to E1 (598±70 s, P≤0.0005). These results demonstrate that match-specific factors reduced particular indices of technical performance in the second half of extra-time. Interventions that seek to maintain skilled performance throughout extra-time warrant further investigation

The role of analytical chemistry in exposure science: Focus on the aquatic environment

Exposure science, in its broadest sense, studies the interactions between stressors (chemical, biological, and physical agents) and receptors (e.g. humans and other living organisms, and non-living items like buildings), together with the associated pathways and processes potentially leading to negative effects on human health and the environment. The aquatic environment may contain thousands of compounds, many of them still unknown, that can pose a risk to ecosystems and human health. Due to the unquestionable importance of the aquatic environment, one of the main challenges in the field of exposure science is the comprehensive characterization and evaluation of complex environmental mixtures beyond the classical/priority contaminants to new emerging contaminants. The role of advanced analytical chemistry to identify and quantify potential chemical risks, that might cause adverse effects to the aquatic environment, is essential. In this paper, we present the strategies and tools that analytical chemistry has nowadays, focused on chromatography hyphenated to (high-resolution) mass spectrometry because of its relevance in this field. Key issues, such as the application of effect direct analysis to reduce the complexity of the sample, the investigation of the huge number of transformation/degradation products that may be present in the aquatic environment, the analysis of urban wastewater as a source of valuable information on our lifestyle and substances we consumed and/or are exposed to, or the monitoring of drinking water, are discussed in this article. The trends and perspectives for the next few years are also highlighted, when it is expected that new developments and tools will allow a better knowledge of chemical composition in the aquatic environment. This will help regulatory authorities to protect water bodies and to advance towards improved regulations that enable practical and efficient abatements for environmental and public health protection