The potential of algal biomass as a source of liquid and gaseous biofuels is a highly topical theme, but as yet there is no successful economically viable commercial system producing biofuel. ...However, the majority of the research has focused on producing fuels from microalgae rather than from macroalgae. This article briefly reviews the methods by which useful energy may be extracted from macroalgae biomass including: direct combustion, pyrolysis, gasification, trans-esterification to biodiesel, hydrothermal liquefaction, fermentation to bioethanol, fermentation to biobutanol and anaerobic digestion, and explores technical and engineering difficulties that remain to be resolved.
A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors ...include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.
Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial ...recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.
An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 PCWG3) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.
PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials.
PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval.
Anthropogenically-modulated reductions in pH, termed ocean acidification, could pose a major threat to the physiological performance, stocks, and biodiversity of calcifiers and may devalue their ...ecosystem services. Recent debate has focussed on the need to develop approaches to arrest the potential negative impacts of ocean acidification on ecosystems dominated by calcareous organisms. In this study, we demonstrate the role of a discrete (i.e. diffusion) boundary layer (DBL), formed at the surface of some calcifying species under slow flows, in buffering them from the corrosive effects of low pH seawater. The coralline macroalga Arthrocardia corymbosa was grown in a multifactorial experiment with two mean pH levels (8.05 'ambient' and 7.65 a worst case 'ocean acidification' scenario projected for 2100), each with two levels of seawater flow (fast and slow, i.e. DBL thin or thick). Coralline algae grown under slow flows with thick DBLs (i.e., unstirred with regular replenishment of seawater to their surface) maintained net growth and calcification at pH 7.65 whereas those in higher flows with thin DBLs had net dissolution. Growth under ambient seawater pH (8.05) was not significantly different in thin and thick DBL treatments. No other measured diagnostic (recruit sizes and numbers, photosynthetic metrics, %C, %N, %MgCO3) responded to the effects of reduced seawater pH. Thus, flow conditions that promote the formation of thick DBLs, may enhance the subsistence of calcifiers by creating localised hydrodynamic conditions where metabolic activity ameliorates the negative impacts of ocean acidification.
Maternal obesity disturbs brain-gut-microbiota interactions and induces negative affect in the offspring, but its impact on gut and brain metabolism in the offspring (F1) are unknown. Here, we tested ...whether perinatal intake of a multispecies probiotic could mitigate the abnormal emotional behavior in the juvenile and adult offspring of obese dams. Untargeted NMR-based metabolomic profiling and gene-expression analysis throughout the gut-brain axis were then used to investigate the biology underpinning behavioral changes in the dams and their offspring. Prolonged high-fat diet feeding reduced maternal gut short-chain fatty acid abundance, increased markers of peripheral inflammation, and decreased the abundance of neuroactive metabolites in maternal milk during nursing. Both juvenile (postnatal day PND 21) and adult (PND112) offspring of obese dams exhibited increased anxiety-like behavior, which were prevented by perinatal probiotic exposure. Maternal probiotic treatment increased gut butyrate and brain lactate in the juvenile and adult offspring and increased the expression of prefrontal cortex
, a marker of glycolytic metabolism in astrocytes.
expression correlated with the increase in gut butyrate in the juvenile and adult offspring. Maternal obesity reduced synaptophysin expression in the adult offspring, while perinatal probiotic exposure increased expression of brain-derived neurotrophic factor. Finally, we showed that the resilience of juvenile and adult offspring to anxiety-like behavior was most prominently associated with increased brain lactate abundance, independent of maternal group. Taken together, we show that maternal probiotic supplementation exerts a long-lasting effect on offspring neuroplasticity and the offspring gut-liver-brain metabolome, increasing resilience to emotional dysfunction induced by maternal obesity.
Abstract Context Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, ...metabolic, cardiovascular, sexual, and cognitive health as well as body composition. Objective To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. Evidence acquisition The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. Evidence synthesis Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). Conclusions ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. Patient summary Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects.
Post-inflammatory behaviours in rodents are widely used to model human depression and to test the efficacy of novel anti-depressants. Mice injected with lipopolysaccharide (LPS) display a ...depressive-like phenotype twenty-four hours after endotoxin administration. Despite the widespread use of this model, the mechanisms that underlie the persistent behavioural changes after the transient peripheral inflammatory response remain elusive. The study of the metabolome, the collection of all the small molecule metabolites in a sample, combined with multivariate statistical techniques provides a way of studying biochemical pathways influenced by an LPS challenge. Adult male CD-1 mice received an intraperitoneal injection of either LPS (0.83 mg/kg) or saline, and were assessed for depressive-like behaviour 24 h later. In a separate mouse cohort, pro-inflammatory cytokine gene expression and 1H nuclear magnetic resonance (NMR) metabolomics measurements were made in brain tissue and blood. Statistical analyses included Independent Sample t-tests for gene expression data, and supervised multi-variate analysis using orthogonal partial least squares discriminant analysis for metabolomics. Both plasma and brain metabolites in male mice were altered following a single peripheral LPS challenge that led to depressive-like behaviour in the forced swim test. The plasma metabolites altered by LPS are involved in energy metabolism, including lipoproteins, glucose, creatine, and isoleucine. In the brain, glutamate, serine, and N-acetylaspartate (NAA) were reduced after LPS, whereas glutamine was increased. Serine-modulated glutamatergic signalling and changes in bioenergetics may mediate the behavioural phenotype induced by LPS. In light of other data supporting a central imbalance of glutamate-glutamine cycling in depression, our results suggest that aberrant central glutaminergic signalling may underpin the depressive-like behaviours that result from both inflammation and non-immune pathophysiology. Normalising glutaminergic signalling, rather than seeking to increase serotonergic signalling, might prove to be a more coherent approach to the development of new treatments for mood disorder.
ABSTRACT
Episodic accretion is one of the competing models to explain the observed luminosity spread in young stellar clusters. These short-lived high accretion events could also have a strong impact ...on planet formation. Observations of high-amplitude variability in young stellar objects (YSOs) due to large changes in the accretion rate provide direct observational evidence for episodic accretion. However, there are still uncertainties in the frequency of these events and if episodic accretion is universal among YSOs. To determine the frequency of outbursts in Class I YSOs, we built a large and robust sample of objects at this evolutionary stage, and searched for high-amplitude near-infrared (ΔKS > 2 mag) variability in the VIRAC2 database of the Vista Variables in the Via Lactea survey. By complementing with near-IR (2MASS and DENIS) and mid-IR (WISE/Neo-WISE) data, we find that from ∼7000 Class I YSOs, 97 objects can be classified as eruptive variable YSOs. The duration of the outbursts vary from a few months to longer than 9 yr, and cover a similar range of amplitudes. Values of ΔKS > 5 mag, however, are only observed in outbursts with duration longer than 9 yr. When considering different effects of completeness and contamination, we estimate that the incidence of episodic accretion in Class I YSOs is between 2 and 3 per cent. Finally, we determine a recurrence time-scale of long-term outbursts (a.k.a FUors) of $\tau =1.75^{+1.12}_{-0.87}$ kyr. The latter value agrees with previous estimates and is in line with the expectations of higher frequency of FUor outbursts during younger stages of evolution.
The derivation of microglia from human stem cells provides systems for understanding microglial biology and enables functional studies of disease-causing mutations. We describe a robust method for ...the derivation of human microglia from stem cells, which are phenotypically and functionally comparable with primary microglia. We used stem cell-derived microglia to study the consequences of missense mutations in the microglial-expressed protein triggering receptor expressed on myeloid cells 2 (TREM2), which are causal for frontotemporal dementia-like syndrome and Nasu-Hakola disease. We find that mutant TREM2 accumulates in its immature form, does not undergo typical proteolysis, and is not trafficked to the plasma membrane. However, in the absence of plasma membrane TREM2, microglia differentiate normally, respond to stimulation with lipopolysaccharide, and are phagocytically competent. These data indicate that dementia-associated TREM2 mutations have subtle effects on microglia biology, consistent with the adult onset of disease in individuals with these mutations.
•Microglia can be efficiently differentiated from human iPSCs•iPSC microglia resemble human primary microglia transcriptionally and functionally•Disease-causing mutations in TREM2 affect receptor processing and expression•TREM2 mutant microglia differentiate, respond to pathogenic stimuli, and phagocytose
Brownjohn and colleagues report methods to generate microglia from induced pluripotent human stem cells, which they demonstrate are highly similar to cultured primary human microglia. Microglia differentiated from patient-derived stem cells carrying neurological disease-causing mutations in the TREM2 receptor differentiate normally and respond appropriately to pathogenic stimuli, despite the absence of functional TREM2 receptor on the plasma membrane.
ABSTRACT
The properties of the Milky Way’s nuclear stellar disc give crucial information on the epoch of bar formation. Mira variables are promising bright candidates to study the nuclear stellar ...disc, and through their period–age relation dissect its star formation history. We report on a sample of 1782 Mira variable candidates across the central $3\times 3\, \mathrm{deg}^2$ of the Galaxy using the multi-epoch infrared VISTA Variables in Via Lactea (VVV) survey. We describe the algorithms employed to select candidate variable stars and then model their light curves using periodogram and Gaussian process methods. By combining with WISE, 2MASS, and other archival photometry, we model the multiband light curves to refine the periods and inspect the amplitude variation between different photometric bands. The infrared brightness of the Mira variables means many are too bright and missed by VVV. However, our sample follows a well-defined selection function as expected from artificial star tests. The multiband photometry is modelled using stellar models with circumstellar dust that characterize the mass-loss rates. We demonstrate how ≳90 per cent of our sample is consistent with O-rich chemistry. Comparison to period–luminosity relations demonstrates that the bulk of the short period stars are situated at the Galactic Centre distance. Many of the longer period variables are very dusty, falling significantly under the O-rich Magellanic Cloud and solar neighbourhood period–luminosity relations and exhibit high mass-loss rates of $\sim 2.5\times 10^{-5}M_\odot \, \mathrm{yr}^{-1}$. The period distribution appears consistent with the nuclear stellar disc forming $\gtrsim 8\, \mathrm{Gyr}$ ago, although it is not possible to disentangle the relative contributions of the nuclear stellar disc and the contaminating bulge.
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