Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of ...artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.
Algae is recognized as a potentially valuable source of biofuels and biochemicals; however, a major limitation to commercialization is in the high cost of harvesting, de-watering, and downstream ...processing of dilute algae biomass when it is grown planktonically. Growing algae as a biofilm offers potential advantages for biomass processing because biofilms are immobilized and orders of magnitude more concentrated. For these reasons there has been an emerging interest in algae biofilm biofuel research over the past several years. Additionally, there has been a considerable amount of work on understanding algae biofilms in nature, and on using algae biofilms for tertiary wastewater treatment. This review paper draws from all of this literature to describe algae biofilm composition, and their growth responses to the key environmental factors affecting growth and internal lipid concentrations; the emphasis being on optimizing biomass and lipid productivity. Additionally, the paper summarizes key things known about planktonic algae growth and bacterial biofilm growth in order to make inferences about the potential growth of algae biofilms. The paper identifies many key knowledge gaps in the potential for producing biomass and lipids from algae biofilm growth systems.
The synapse in traumatic brain injury Jamjoom, Aimun A B; Rhodes, Jonathan; Andrews, Peter J D ...
Brain (London, England : 1878),
02/2021, Volume:
144, Issue:
1
Journal Article
Peer reviewed
Open access
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and is a risk factor for dementia later in life. Research into the pathophysiology of TBI has focused on the impact ...of injury on the neuron. However, recent advances have shown that TBI has a major impact on synapse structure and function through a combination of the immediate mechanical insult and the ensuing secondary injury processes, leading to synapse loss. In this review, we highlight the role of the synapse in TBI pathophysiology with a focus on the confluence of multiple secondary injury processes including excitotoxicity, inflammation and oxidative stress. The primary insult triggers a cascade of events in each of these secondary processes and we discuss the complex interplay that occurs at the synapse. We also examine how the synapse is impacted by traumatic axonal injury and the role it may play in the spread of tau after TBI. We propose that astrocytes play a crucial role by mediating both synapse loss and recovery. Finally, we highlight recent developments in the field including synapse molecular imaging, fluid biomarkers and therapeutics. In particular, we discuss advances in our understanding of synapse diversity and suggest that the new technology of synaptome mapping may prove useful in identifying synapses that are vulnerable or resistant to TBI.
The identification of somatic mutations in the gene encoding the serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for ...this disease.
We conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as RG7204), an orally available inhibitor of mutated BRAF, followed by an extension phase involving the maximum dose that could be administered without adverse effects (the recommended phase 2 dose). Patients received PLX4032 twice daily until they had disease progression. Pharmacokinetic analysis and tumor-response assessments were conducted in all patients. In selected patients, tumor biopsy was performed before and during treatment to validate BRAF inhibition.
A total of 55 patients (49 of whom had melanoma) were enrolled in the dose-escalation phase, and 32 additional patients with metastatic melanoma who had BRAF with the V600E mutation were enrolled in the extension phase. The recommended phase 2 dose was 960 mg twice daily, with increases in the dose limited by grade 2 or 3 rash, fatigue, and arthralgia. In the dose-escalation cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a partial response and 1 had a complete response. Among the 32 patients in the extension cohort, 24 had a partial response and 2 had a complete response. The estimated median progression-free survival among all patients was more than 7 months.
Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients. (Funded by Plexxikon and Roche Pharmaceuticals.)
There has been considerable interest in the use of red seaweed, and in particular Asparagopsis taxiformis, to increase production of cattle and to reduce greenhouse gas emissions. We hypothesized ...that feeding seaweed or seaweed derived products would increase beef or dairy cattle performance as indicated by average daily gain (ADG), feed efficiency measures, milk production, and milk constituents, and reduce methane emissions. We used meta-analytical methods to evaluate these hypotheses. A comprehensive search of Google Scholar, Pubmed and ISI Web of Science produced 14 experiments from which 23 comparisons of treatment effects could be evaluated. Red seaweed (Asparagopsis taxiformis) and brown seaweed (Ascophyllum nodosum) were the dominant seaweeds used. There were no effects of treatment on ADG or dry matter intake (DMI). While there was an increase in efficiency for feed to gain by 0.38 kg per kg standardized mean difference (SMD) = 0.56; P = 0.001 on DerSimonian and Laird (D&L) evaluation, neither outcome was significant using the more rigorous robust regression analysis (P >0.06). The type of seaweed used was not a significant covariable for ADG and DMI, but A. nodosum fed cattle had lesser feed to gains efficiency compared to those fed A. taxiformis. Milk production was increased with treatment on weighted mean difference (WMD; 1.35 ± 0.44 kg/d; P 80%). In one comparison, methane yield was reduced by 97%. We conclude that while there was evidence of potential for benefit from seaweed use to improve production and reduce methane yield more in vivo experiments are required to strengthen the evidence of effect and identify sources of heterogeneity in methane response, while practical applications and potential risks are evaluated for seaweed use.
The development of more efficient electrical storage is a pressing requirement to meet future societal and environmental needs. This demand for more sustainable, efficient energy storage has provoked ...a renewed scientific and commercial interest in advanced capacitor designs in which the suite of experimental techniques and ideas that comprise nanotechnology are playing a critical role. Capacitors can be charged and discharged quickly and are one of the primary building blocks of many types of electrical circuit, from microprocessors to large-sale power supplies, but usually have relatively low energy storage capability when compared with batteries. The application of nanostructured materials with bespoke morphologies and properties to electrochemical supercapacitors is being intensively studied in order to provide enhanced energy density without comprising their inherent high power density and excellent cyclability. In particular, electrode materials that exploit physical adsorption or redox reactions of electrolyte ions are foreseen to bridge the performance disparity between batteries with high energy density and capacitors with high power density. In this review, we present some of the novel nanomaterial systems applied for electrochemical supercapacitors and show how material morphology, chemistry and physical properties are being tailored to provide enhanced electrochemical supercapacitor performance.
Background The purpose of this study was to perform a systematic review and meta-analysis of all available level I randomized controlled trials comparing single-row with double-row repair to ...statistically compare clinical outcomes and imaging-diagnosed re-tear rates. Methods A literature search was undertaken to identify all level I randomized controlled trials comparing structural or clinical outcomes after single-row versus double-row rotator cuff repair. Clinical outcomes measures included in the meta-analysis were the American Shoulder and Elbow Surgeons, University of California–Los Angeles, and Constant scores; structural outcomes included imaging-confirmed re-tears. Meta-analyses compared raw mean differences in outcomes measures and relative risk ratios for imaging-diagnosed re-tears after single-row or double-row repairs by a random-effects model. Results The literature search identified a total of 7 studies that were included in the meta-analysis. There were no significant differences in preoperative to postoperative change in American Shoulder and Elbow Surgeons, University of California–Los Angeles, or Constant scores between the single-row and double-row groups ( P = .440, .116, and .156, respectively). The overall re-tear rate was 25.9% (68/263) in the single-row group and 14.2% (37/261) in the double-row group. There was a statistically significant increased risk of sustaining an imaging-proven re-tear of any type in the single-row group (relative risk, 1.76 95% confidence interval, 1.25-2.48; P = .001), with partial-thickness re-tears accounting for the majority of this difference (relative risk, 1.99 95% confidence interval, 1.40-3.82; P = .039). Conclusion Single-row repairs resulted in significantly higher re-tear rates compared with double-row repairs, especially with regard to partial-thickness re-tears. However, there were no detectable differences in improvement in outcomes scores between single-row and double-row repairs.
PARP1 regulates the repair of DNA single-strand breaks generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we ...report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication-associated DNA damage owing to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and by stabilising replication forks that encounter BER intermediates.
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