Indigenous microbial surrogates in wastewater used to understand public health risk expressed in the Disability-Adjusted Life Year (DALY) metric

In any wastewater recycling scheme, the protection of public health is of primary importance. In Australia, the public health requirements applying to the treatment of recycled water are stringent. They use the Disability-Adjusted Life Year (DALY) metric to set a level of negligible public health risk. The target maximum risk of 10-6 DALY per person per year has been adopted in Australian water recycling guidelines since 2006. A key benefit of the DALY approach is its ability to standardise the understanding of risk across disparate areas of public health. To address the key challenge of translating the results of monitoring of microorganisms in the recycled water into this quantitative public health metric, we have developed a novel method. This paper summarises an approach where microbial surrogate organisms indigenous to wastewater are used to measure the efficiency of water recycling treatment processes and estimate public health risk. An example of recent implementation in the Greater Sydney region of Australia is provided

Monthly quasi-periodic eruptions from repeated stellar disruption by a massive black hole

In recent years, searches of archival X-ray data have revealed galaxies exhibiting nuclear quasi-periodic eruptions with periods of several hours. These are reminiscent of the tidal disruption of a star by a supermassive black hole. The repeated, partial stripping of a white dwarf in an eccentric orbit around an ~105 M⊙ black hole provides an attractive model. A separate class of periodic nuclear transients, with much longer timescales, have recently been discovered optically and may arise from the partial stripping of a main-sequence star by an ~107 M⊙ black hole. No clear connection between these classes has been made. We present the discovery of an X-ray nuclear transient that shows quasi-periodic outbursts with a period of weeks. We discuss possible origins for the emission and propose that this system bridges the two existing classes outlined above. This discovery was made possible by the rapid identification, dissemination and follow-up of an X-ray transient found by the new live Swift-XRT transient detector, demonstrating the importance of low-latency, sensitive searches for X-ray transients

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour

available in PMC 2012 June 22.Heritable variation in behavioural traits generally has a complex genetic basis1, and thus naturally occurring polymorphisms that influence behaviour have been defined in only rare instances2,3. The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species4 and provided insights into its diverse microbial ecology5. C. elegans responds to bacterial infection with conserved innate immune responses6-8 and, while lacking the immunological memory of vertebrate adaptive immunity, exhibits an aversive learning response to pathogenic bacteria9. Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuronspecific rescue and ablation experiments, and genetic interaction analysis suggest that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-110, which we have previously shown promotes P. aeruginosa lawn avoidance behaviour11. Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens.National Institutes of Health (U.S.) (NIH Grant GM084477

Structure and Dynamics of the G121V Dihydrofolate Reductase Mutant: Lessons from a Transition-State Inhibitor Complex

It is well known that enzyme flexibility is critical for function. This is due to the observation that the rates of intramolecular enzyme motions are often matched to the rates of intermolecular events such as substrate binding and product release. Beyond this role in progression through the reaction cycle, it has been suggested that enzyme dynamics may also promote the chemical step itself. Dihydrofolate reductase (DHFR) is a model enzyme for which dynamics have been proposed to aid in both substrate flux and catalysis. The G121V mutant of DHFR is a well studied form that exhibits a severe reduction in the rate of hydride transfer yet there remains dispute as to whether this defect is caused by altered structure, dynamics, or both. Here we address this by presenting an NMR study of the G121V mutant bound to reduced cofactor and the transition state inhibitor, methotrexate. NMR chemical shift markers demonstrate that this form predominantly adopts the closed conformation thereby allowing us to provide the first glimpse into the dynamics of a catalytically relevant complex. Based on 15N and 2H NMR spin relaxation, we find that the mutant complex has modest changes in ps-ns flexibility with most affected residues residing in the distal adenosine binding domain rather than the active site. Thus, aberrant ps-ns dynamics are likely not the main contributor to the decreased catalytic rate. The most dramatic effect of the mutation involves changes in µs-ms dynamics of the F-G and Met20 loops. Whereas loop motion is quenched in the wild type transition state inhibitor complex, the F-G and Met20 loops undergo excursions from the closed conformation in the mutant complex. These excursions serve to decrease the population of conformers having the correct active site configuration, thus providing an explanation for the G121V catalytic defect

Acquiring a pet dog significantly reduces stress of primary carers for children with autism spectrum disorder: a prospective case control study

This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3–10 weeks after acquisition) and follow-up (25–40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD

Monthly quasi-periodic eruptions from repeated stellar disruption by a massive black hole

In recent years, searches of archival X-ray data have revealed galaxies exhibiting nuclear quasi-periodic eruptions with periods of several hours. These are reminiscent of the tidal disruption of a star by a supermassive black hole, and the repeated, partial stripping of a white dwarf in an eccentric orbit around a∼105M⊙ black hole provides an attractive model. A separate class of periodic nuclear transients, with significantly longer timescales, have recently been discovered optically, and may arise from the partial stripping of a main-sequence star by a∼107M⊙black hole. No clear connection between these classes has been made. We present the discovery of an X-ray nuclear transient which shows quasi periodic outbursts with a period of weeks. We discuss possible origin for the emission, and propose that this system bridges the two existing classes outlined above. This discovery was made possible by the rapid identification, dissemination and follow up of an Xray transient found by the new live Swift-XRT transient detector, demonstrating the importance of low-latency, sensitive searches for X-ray transients

Factors affecting health-related quality of life in Thai children with thalassemia

<p>Abstract</p> <p>Background</p> <p>Knowledge of the factors associated with health-related quality of life (HRQOL) among patients with thalassemia is essential in developing more suitable clinical, counseling, and social support programs to improve treatment outcomes of these patients. In light of the limited research in this area, this study aims to examine factors associated with HRQOL among children and adolescents with thalassemia in Thailand.</p> <p>Methods</p> <p>A cross-sectional survey was conducted in three selected hospitals in Thailand during June to November 2006. PedsQL™ 4.0 Generic Core Scale (Thai version) was used to assess HRQOL in 315 thalassemia patients between 5 and 18 years of age. Other related clinical characteristics of the patients were collected via medical record review.</p> <p>Results</p> <p>The mean (SD) of the total summary score was 76.67 (11.40), while the means (SD) for the Physical Health Summary score and Psychosocial Health Summary score were 78.24 (14.77) and 75.54 (12.76), respectively. The school functioning subscale scored the lowest, with a mean of 67.89 (SD = 15.92). The following factors significantly affected the HRQOL of the patients: age; age at onset of anemia and age at first transfusion; pre-transfusion hemoglobin (Hb) level; receiving a blood transfusion during the previous three months; and disease severity. In addition, iron chelation therapy had a significant negative effect on HRQOL in the school functioning subscale. In contrast, serum ferritin level, frequency of blood transfusions per year, and gender were not significantly related to HRQOL among these patients. The results from multivariate analysis also confirmed these findings.</p> <p>Conclusions</p> <p>To improve HRQOL of thalassemia patients, suitable programs aimed at providing psychosocial support and a link between the patient, school officials, the family and the physician are important, especially in terms of improving the school functioning score. The findings also confirmed the importance of maintaining a pre-transfusion Hb level of at least 9-10.5 g/dL. In addition, special care and attention should be given to patients with a severe condition, and those who are receiving subcutaneous iron chelation therapy.</p

Swift Multiwavelength Follow-up of LVC S200224ca and the Implications for Binary Black Hole Mergers

On 2020 February 24, during their third observing run ("O3"), the Laser Interferometer Gravitational-wave Observatory and Virgo Collaboration detected S200224ca: a candidate gravitational wave (GW) event produced by a binary black hole (BBH) merger. This event was one of the best-localized compact binary coalescences detected in O3 (with 50%/90% error regions of 13/72 deg2), and so the Neil Gehrels Swift Observatory performed rapid near-UV/X-ray follow-up observations. Swift-XRT and UVOT covered approximately 79.2% and 62.4% (respectively) of the GW error region, making S200224ca the BBH event most thoroughly followed-up in near-UV (u-band) and X-ray to date. No likely EM counterparts to the GW event were found by the Swift BAT, XRT, or UVOT, nor by other observatories. Here, we report on the results of our searches for an EM counterpart, both in the BAT data near the time of the merger, and in follow-up UVOT/XRT observations. We also discuss the upper limits we can place on EM radiation from S200224ca, as well as the implications these limits have on the physics of BBH mergers. Namely, we place a shallow upper limit on the dimensionless BH charge, $\hat{q}\lt 1.4\times {10}^{-4}$, and an upper limit on the isotropic-equivalent energy of a blast wave E < 4.1 × 1051 erg (assuming typical GRB parameters)

Swift-XRT follow-up of gravitational wave triggers during the third aLIGO/Virgo observing run

The Neil Gehrels Swift Observatory followed up 18 gravitational wave (GW) triggers from the LIGO/Virgo collaboration during the O3 observing run in 2019/2020, performing approximately 6500 pointings in total. Of these events, four were finally classified (if real) as binary black hole (BH) triggers, six as binary neutron star (NS) events, two each of NSBH and Mass Gap triggers, one an unmodelled (Burst) trigger, and the remaining three were subsequently retracted. Thus far, four of these O3 triggers have been formally confirmed as real gravitational wave events. While no likely electromagnetic counterparts to any of these GW events have been identified in the X-ray data (to an average upper limit of 3.60 x 10^{-12} erg cm^{-2} s^{-1} over 0.3-10 keV), or at other wavelengths, we present a summary of all the Swift-XRT observations performed during O3, together with typical upper limits for each trigger observed. The majority of X-ray sources detected during O3 were previously uncatalogued; while some of these will be new (transient) sources, others are simply too faint to have been detected by earlier survey missions such as ROSAT. The all-sky survey currently being performed by eROSITA will be a very useful comparison for future observing runs, reducing the number of apparent candidate X-ray counterparts by up to 95 per cent